Asfiled with the Securities and Exchange Commission on August 4, 2025

RegistrationNo. 333-

UNITEDSTATES

SECURITIESAND EXCHANGE COMMISSION

Washington,D.C. 20549

FORMS-1

REGISTRATIONSTATEMENT UNDER THE SECURITIES ACT OF 1933

401Professional Drive, Suite 260

Gaithersburg, MD 20879 (240) 430-4212

(Address,including zip code, and telephone number,

includingarea code, of registrant’s principal executive offices)

ChristopherCooper

InterimChief Executive Officer

ShuttlePharmaceuticals Holdings, Inc.

401Professional Drive, Suite 260

Gaithersburg, MD 20879 (240) 430-4212

(Name,address, including zip code, and telephone number,

includingarea code, of agent for service)

Copiesto:

RossCarmel, Esq.

JeffCahlon, Esq.

SichenziaRoss Ference Carmel LLP

1185Avenue of the Americas, 31st Floor

NewYork, New York 10036

Tel:(212) 930-9700

Fromtime to time after this registration statement becomes effective.

(Approximatedate of commencement of proposed sale to the public)

Ifany of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under theSecurities Act of 1933 check the following box. ☒

Ifthis Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the followingbox and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.☐

Ifthis Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list theSecurities Act registration statement number of the earlier effective registration statement for the same offering. ☐

Ifthis Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list theSecurities Act registration statement number of the earlier effective registration statement for the same offering. ☐

Indicateby check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company,or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smallerreporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Ifan emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complyingwith any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

TheRegistrant hereby amends this Registration Statement on such date or dates as may be necessary to delay its effective date until theRegistrant shall file a further amendment which specifically states that this Registration Statement shall thereafter become effectivein accordance with Section 8(a) of the Securities Act of 1933, as amended, or until the Registration Statement shall become effectiveon such date as the Securities and Exchange Commission, acting pursuant to Section 8(a), may determine.

Theinformation in this preliminary prospectus is not complete and may be changed. These securities may not be sold until the registrationstatement filed with the Securities and Exchange Commission is effective. This preliminary prospectus is not an offer to sell nor doesit seek an offer to buy these securities in any state or other jurisdiction where the offer or sale is not permitted.

ShuttlePharmaceuticals Holdings, Inc.

1,180,877Shares of Common Stock

Pursuantto this prospectus, the selling stockholder identified herein is offering on a resale basis 1,180,877 shares of common stock of ShuttlePharmaceuticals Holdings, Inc., consisting of (i) 21,924 outstanding shares and (ii) 1,158,953 shares issuable upon exercise of pre-fundedwarrants, each exercisable into one share of common stock at a nominal exercise price per share of $0.001, without expiration. The outstandingshares of common stock and the pre-funded warrants were issued to the selling stockholder in connection with a private placement we completedon June 24, 2025. We will not receive any of the proceeds from the sale by the selling stockholder of the shares.

Theselling stockholder may sell or otherwise dispose of the shares covered by this prospectus in a number of different ways and atvarying prices. We provide more information about how the selling stockholder may sell or otherwise dispose of the shares covered bythis prospectus in the section entitled “Plan of Distribution” on page 7. Discounts, concessions,commissions and similar selling expenses attributable to the sale of shares covered by this prospectus will be borne by the sellingstockholder. We will pay all expenses (other than discounts, concessions, commissions and similar selling expenses) relating to theregistration of the shares with the Securities and Exchange Commission, or the SEC.

Youshould carefully read this prospectus, together with the documents we incorporate by reference, before you invest in our common stock.

Ourcommon stock is listed on The Nasdaq Capital Market under the symbol “SHPH.” On August 1, 2025, the last reportedsale price for our common stock was $3.50 per share.

Investingin our common stock involves substantial risk. Please read “Risk Factors” beginning on page 6 of this prospectus and inthe documents we incorporate by reference.

Neitherthe SEC nor any state securities commission has approved or disapproved of these securities or passed upon the accuracy or adequacy ofthis prospectus. Any representation to the contrary is a criminal offense.

Thedate of this prospectus is ____, 2025

TABLEOF CONTENTS

ABOUTTHIS PROSPECTUS

Thisprospectus is part of a registration statement that we have filed with the SEC pursuant to which the selling stockholder named hereinmay, from time to time, offer and sell or otherwise dispose of the shares of our common stock covered by this prospectus. You shouldnot assume that the information contained in this prospectus is accurate on any date subsequent to the date set forth on the front coverof this prospectus or that any information we have incorporated by reference is correct on any date subsequent to the date of the documentincorporated by reference, even though this prospectus is delivered or shares of common stock are sold or otherwise disposed of on alater date. It is important for you to read and consider all information contained in this prospectus, including the documents incorporatedby reference therein, in making your investment decision. You should also read and consider the information in the documents to whichwe have referred you under “Where You Can Find More Information” and “Information Incorporated by Reference”in this prospectus.

Wehave not authorized anyone to give any information or to make any representation to you other than those contained or incorporated byreference in this prospectus. You must not rely upon any information or representation not contained or incorporated by reference inthis prospectus. This prospectus does not constitute an offer to sell or the solicitation of an offer to buy any of our shares of commonstock other than the shares of our common stock covered hereby, nor does this prospectus constitute an offer to sell or the solicitationof an offer to buy any securities in any jurisdiction to any person to whom it is unlawful to make such offer or solicitation in suchjurisdiction. Persons who come into possession of this prospectus in jurisdictions outside the United States are required to inform themselvesabout, and to observe, any restrictions as to the offering and the distribution of this prospectus applicable to those jurisdictions.

Asused in this prospectus and unless otherwise indicated, the terms “we,” “us,” “our,” “ShuttlePharma,” or the “Company” refer to Shuttle Pharmaceuticals Holdings, Inc. and its consolidated subsidiaries.

Allshare amounts in this prospectus give effect to our 1-for-25 reverse stock split effected on June 16, 2025, unless otherwise indicated.

SUMMARY

AboutUs—Business Overview

Foundedby Georgetown University Medical School faculty members, Shuttle Pharmaceuticals Holdings, Inc. is a discovery and development stagepharmaceutical company leveraging our proprietary technology to develop novel therapies that are designed to cure cancer. Originallyformed as Shuttle Pharmaceuticals, LLC in 2012, our goal is to extend the benefits of cancer treatments by leveraging insights into cancertherapy with surgery, radiation therapy, chemotherapy and immunotherapy. While there are several therapies being developed with the goalof curing cancer, one of the most effective and proven approaches to this is radiation therapy (“RT”). We are developinga pipeline of products designed to address the limitations of the current standard of cancer therapies. We believe that our product candidateswill enable us to deliver cancer treatments that are safer, more reliable and at a greater scale than that of the current standard ofcare.

Ouroperations to date have focused on continuing our research and development efforts to advance Ropidoxuridine clinical testing and improveddrug formulation, to advance HDAC6 inhibitor (SP-2-225) preclinical development and explore the application of the PC-RAD Test, predictivebiomarkers of radiation response. The clinical development of Ropidoxuridine has included completion of a Phase I clinical trial to establishdrug bioavailability and a maximum tolerated dose for use in Phase II clinical trials. TCG GreenChem, with whom we have contracted forprocess research, development and cGMP compliant manufacture of IPdR, has manufactured the API of Ropidoxuridine and the University ofIowa Pharmaceuticals has formulated the drug product for use in our current Phase II clinical trial in brain cancer patients undergoingradiation therapy. The drug product (capsules) were shipped to CRO Theradex Oncology and distributed to clinical trial sites that arefully approved to enroll patients in the trial. Shuttle Pharma received approval from the FDA to begin the clinical trial. The FDA thereaftermade recommendations to expand the clinical trial to include a randomized dose “optimization” step and we agreed with therecommendation. Meetings with engaged clinical sites to review the protocol documents have occurred and FDA required IRB approvals havebeen received. With FDA recommended changes incorporated into the revised protocol and the completion of site initiation visits, we commencedour Phase II clinical study in October 2024. The Company’s radiation biomarker project and the health disparities project havebeen completed and we are proceeding with plans for clinical validation and potential for commercialization of Ropidoxuridine as a radiationsensitizer.

CorporateInformation

TheCompany was formed as a limited liability company in the state of Maryland in December 2012 and was converted to a C corporation in August2016. In June 2018, we completed a share exchange with Shuttle Pharma Acquisition Corp. Inc. (“Acquisition Corp.”), pursuantto which Shuttle Pharmaceuticals, Inc. became a subsidiary of Acquisition Corp. and we subsequently changed the name of Acquisition Corp.to Shuttle Pharmaceuticals Holdings, Inc.

Ourexecutive offices are located at 401 Professional Drive, Suite 260, Gaithersburg, MD 20879 and our telephone number is (240) 430-4212.Our corporate website is www.shuttlepharma.com. Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form8-K, and all amendments to those reports, if any, are available to you free of charge through the “Investor Relations” sectionof our website as soon as reasonably practicable after such materials have been electronically filed with or furnished to the SEC. Informationcontained on our website does not form a part of this prospectus.

PrivatePlacement

OnJune 20, 2025, we entered into a securities purchase agreement with an accredited investor, for the sale by the Company to the investor,in a private placement, of 21,924 shares of common stock and 1,158,953 pre-funded warrants to purchase shares of common stock, at a purchaseprice of $3.60 per share or $3.599 per pre-funded warrant. The private placement closed on June 24, 2025.

Thepre-funded warrants are immediately exercisable, at a nominal exercise price of $0.001, and may be exercised at any time until all ofthe pre-funded warrants are exercised in full. The pre-funded warrants may not be exercised to the extent such exercise would resultin the holder beneficially owning more than 4.99% of the Company’s outstanding common stock.

Inconnection with the purchase agreement, the Company entered into a registration rights agreement with the investor. Pursuant to theregistration rights agreement, the Company agreed to file a registration statement with the SEC to register for resale the shares ofcommon stock, and the shares issuable upon exercise of the pre-funded warrants issued under the purchase agreement, within 10 daysof the closing date, and to have such registration statement declared effective within 90 days of the closing date (or 120 days ifthe registration statement is reviewed by the SEC). The registration rights agreement provided that the Company would beobligated to pay certain liquidated damages to the investor if the Company failed to file the resale registration statement, or tohave such registration statement declared effective by such dates. The Company was prepared to file the registration statementwithin the deadline required under the registration rights agreement and its failure to do so within such deadline was due to arequest by the investor. The Company has interpreted such request by the investor as a waiver of any liquidated damages underthe registration rights agreement with respect to the Company’s failure to file the registration statement within 10 days ofthe closing date.

WestParkCapital, Inc. (“WestPark”) acted as the placement agent in connection with the private placement pursuant to an engagementagreement between the Company and WestPark, as amended (as amended, the “Engagement Agreement”). Pursuant to the EngagementAgreement, the Company paid WestPark a fee of 4% of the gross proceeds received by the Company in the private placement. The Companyalso reimbursed certain expenses of WestPark.

Thisprospectus covers the resale of the 21,924 shares and 1,158,953 shares issuable upon exercise of the pre-funded warrants issued underthe purchase agreement.

RISKFACTORS

Aninvestment in our securities involves a high degree of risk. Before deciding whether to invest in our securities, you should considercarefully the risks and uncertainties discussed below, as well as those under the heading “Risk Factors” contained in ourmost recent annual report on Form 10-K filed with the SEC, and as incorporated by reference in this prospectus, as the same may be amended,supplemented or superseded by the risks and uncertainties described under similar headings in the other documents that are filed by usafter the date hereof and incorporated by reference into this prospectus. Please also read carefully the section below titled “CautionaryNote Regarding Forward-Looking Statements.”

Thesale of a substantial amount of our common stock, including resale of the shares of common stock by the selling stockholder in the publicmarket, could adversely affect the market price of our common stock.

Weare registering for resale 1,180,877 shares of common stock, including 1,158,953 shares issuable upon the exercise of pre-funded warrantsheld by the selling stockholder. Sales of substantial amounts of our common stock in the public market, or the perception that such salesmight occur, could adversely affect the market price of our common stock. We cannot predict if and when the selling stockholder may sellsuch shares in the public market.

CAUTIONARYNOTE REGARDING FORWARD-LOOKING STATEMENTS

Allstatements in this prospectus and the documents incorporated by reference that are not historical facts should be considered “ForwardLooking Statements” within the meaning of the “Safe Harbor” provisions of the Private Securities Litigation ReformAct of 1995. Such statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performanceor achievements of the Company to be materially different from any future results, performance or achievements expressed or implied bythe forward-looking statements. Some of the forward-looking statements can be identified by the use words such as “believe,”“expect,” “may,” “estimates,” “should,” “seek,” “approximately,”“intend,” “plan,” “estimate,” “project,” “continue” or “anticipates”or similar expressions or words, or the negatives of those expressions or words. These statements may be made directly in this prospectusand they may also be incorporated by reference in this prospectus from other documents filed with the SEC, and include, but are not limitedto, statements about future financial and operating results and performance, statements about our plans, objectives, expectations andintentions with respect to future operations and products, and other statements that are not historical facts. These forward-lookingstatements are based upon the current beliefs and expectations of our management and are inherently subject to significant business,economic and competitive uncertainties and contingencies, many of which are difficult to predict and generally beyond our control. Inaddition, these forward-looking statements are subject to assumptions with respect to future business strategies and decisions that aresubject to change. Actual results may differ materially from the anticipated results discussed in these forward-looking statements asa result of several factors including, but not limited to, those noted under “Risk Factors” in this prospectus and in thedocuments incorporated by reference in this prospectus.

USEOF PROCEEDS

Wewill not receive any of the proceeds from any sale or other disposition of the shares of common stock covered by this prospectus. Allproceeds from the sale of the shares will be paid directly to the selling stockholder.

SELLINGSTOCKHOLDER

Theshares of common stock being offered by the selling stockholder are those shares previously issued to the selling stockholder and sharesunderlying the pre-funded warrants issued to the selling stockholder under the purchase agreement between us and the selling stockholder,dated June 20, 2025 (see “Summary—Private Placement”). We are registering the shares of common stock in order to permitthe selling stockholder to offer the shares for resale from time to time. Except for the ownership of the shares of common stock andas otherwise disclosed in this prospectus, the selling stockholder has not had any material relationship with us within the past threeyears. The selling stockholder is not a broker-dealer or an affiliate of a broker-dealer.

Thetable below lists the selling stockholder and other information regarding the beneficial ownership of the shares of common stock by theselling stockholder. The second column lists the number of shares of common stock beneficially owned by the selling stockholder, as ofAugust 1, 2025. The third column lists the shares of common stock being offered by this prospectus by the selling stockholder.

Inaccordance with the terms of a registration rights agreement with the selling stockholder, this prospectus covers the resale of the numberof shares of common stock and shares underlying pre-funded warrants issued to the selling stockholder under the purchase agreement. Thefourth column assumes the sale of all of the shares offered by the selling stockholder pursuant to this prospectus.

Theselling stockholder may sell all, some or none of its shares in this offering. See “Plan of Distribution.”

(1)Under applicable SEC rules, a person is deemed to beneficially own securities which the person has the right to acquire within 60 daysthrough the exercise of any option or warrant or through the conversion of a convertible security. Also under applicable SEC rules, aperson is deemed to be the “beneficial owner” of a security with regard to which the person directly or indirectly, has orshares (a) voting power, which includes the power to vote or direct the voting of the security, or (b) investment power, which includesthe power to dispose, or direct the disposition, of the security, in each case, irrespective of the person’s economic interestin the security. To our knowledge, subject to community property laws where applicable, the selling stockholder named in the table hassole voting and investment power with respect to the common stock shown as beneficially owned by the selling stockholder, except as otherwiseset forth in the footnotes to the table.

(2)Represents the amount of shares that will be held by the selling stockholder after completion of this offering based on the assumptionsthat (a) all shares of common stock offered for resale under this prospectus will be sold and (b) no other shares of common stock areacquired or sold by the selling stockholder prior to completion of this offering. However, the selling stockholder may sell all, someor none of such shares offered pursuant to this prospectus.

(3)Based on 1,070,773 shares of common stock outstanding as of August 1, 2025.

(4)Connor Yuen has voting and dispositive power over the shares. The address of the selling stockholder is 850 New Burton Road, Suite201, Dover, DE 19904.

(5)Includes 1,158,953 shares issuable upon exercise of pre-funded warrants. The pre-funded warrants cannot be exercised to the extent suchexercise would result in the holder beneficially owning more than 4.99% of the Company’s common stock. The ownership amount inthe table does not give effect to such beneficial ownership limitation.

PLANOF DISTRIBUTION

Theselling stockholder and any of its pledgees, assignees and successors-in-interest may, from time to time, sell any or all of its securitiescovered hereby on the Nasdaq Capital Market or any other stock exchange, market or trading facility on which the securities are tradedor in private transactions. These sales may be at fixed or negotiated prices. The selling stockholder may use any one or more of thefollowing methods when selling securities:

Theselling stockholder may also sell securities under Rule 144 or any other exemption from registration under the Securities Act of 1933,as amended, or the Securities Act, if available, rather than under this prospectus.

Broker-dealersengaged by the selling stockholder may arrange for other brokers-dealers to participate in sales. Broker-dealers may receive commissionsor discounts from the selling stockholder (or, if any broker-dealer acts as agent for the purchaser of securities, from the purchaser)in amounts to be negotiated, but, except as set forth in a supplement to this prospectus, in the case of an agency transaction not inexcess of a customary brokerage commission in compliance with FINRA Rule 2121; and in the case of a principal transaction a markup ormarkdown in compliance with FINRA Rule 2121.

Inconnection with the sale of the securities or interests therein, the selling stockholder may enter into hedging transactions with broker-dealersor other financial institutions, which may in turn engage in short sales of the securities in the course of hedging the positions theyassume. The selling stockholder may also sell securities short and deliver these securities to close out its short positions, or loanor pledge the securities to broker-dealers that in turn may sell these securities. The selling stockholder may also enter into optionor other transactions with broker-dealers or other financial institutions or create one or more derivative securities which require thedelivery to such broker-dealer or other financial institution of securities offered by this prospectus, which securities such broker-dealeror other financial institution may resell pursuant to this prospectus (as supplemented or amended to reflect such transaction).

Theselling stockholder and any broker-dealers or agents that are involved in selling the securities may be deemed to be “underwriters”within the meaning of the Securities Act in connection with such sales. In such event, any commissions received by such broker-dealersor agents and any profit on the resale of the securities purchased by them may be deemed to be underwriting commissions or discountsunder the Securities Act. The selling stockholder has informed the Company that it does not have any written or oral agreement or understanding,directly or indirectly, with any person to distribute the securities.

TheCompany is required to pay certain fees and expenses incurred by the Company incident to the registration of the securities. The Companyhas agreed to indemnify the selling stockholder against certain losses, claims, damages and liabilities, including liabilities underthe Securities Act.

Weagreed to keep this prospectus effective until (i) the date on which the securities may be resold by the selling stockholder withoutregistration and without regard to any volume or manner-of-sale limitations by reason of Rule 144 without the requirement for the Companyto be in compliance with the current public information under Rule 144 under the Securities Act or any other rule of similar effect or(ii) all of the securities have been sold pursuant to this prospectus or Rule 144 under the Securities Act or any other rule of similareffect. The resale securities will be sold only through registered or licensed brokers or dealers if required under applicable statesecurities laws. In addition, in certain states, the resale securities covered hereby may not be sold unless they have been registeredor qualified for sale in the applicable state or an exemption from the registration or qualification requirement is available and iscomplied with.

Underapplicable rules and regulations under the Securities Exchange Act of 1934, as amended, or the Exchange Act, any person engaged in thedistribution of the resale securities may not, subject to certain exceptions, simultaneously engage in market making activities withrespect to the common stock for the applicable restricted period, as defined in Regulation M, prior to the commencement of the distribution.In addition, the selling stockholder will be subject to applicable provisions of the Exchange Act and the rules and regulations thereunder,including Regulation M, which may limit the timing of purchases and sales of the common stock by the selling stockholder or any otherperson. We will make copies of this prospectus available to the selling stockholder and have informed it of the need to deliver a copyof this prospectus to each purchaser at or prior to the time of the sale (including by compliance with Rule 172 under the SecuritiesAct).

LEGALMATTERS

Thevalidity of the shares of common stock offered in this prospectus has been passed upon for us by Sichenzia Ross Ference Carmel LLP, NewYork, New York.

EXPERTS

Theconsolidated financial statements of Shuttle Pharmaceuticals Holdings, Inc. as of and for the years ended December 31, 2024 and 2023incorporated by reference in this prospectus and in the registration statement of which this prospectus forms a part, have been so incorporatedin reliance on the report of Forvis Mazars, LLP, an independent registered public accounting firm. Such consolidated financial statementshave been incorporated herein in reliance upon such report given on the authority of such firm as experts in accounting and auditing.The report of Forvis Mazars, LLP contains an explanatory paragraph regarding substantial doubt about the Company’s ability to continueas a going concern.

INFORMATIONINCORPORATED BY REFERENCE

TheSEC allows us to “incorporate by reference” information that we file with them. Incorporation by reference allows us to discloseimportant information to you by referring you to those other documents. The information incorporated by reference is an important partof this prospectus, and information that we file later with the SEC will automatically update and supersede this information. We fileda registration statement on Form S-1 under the Securities Act with the SEC with respect to the securities being offered pursuant to thisprospectus. This prospectus omits certain information contained in the registration statement, as permitted by the SEC. You should referto the registration statement, including the exhibits and schedules attached to the registration statement and the information incorporatedby reference, for further information about us and the securities being offered pursuant to this prospectus. The documents we are incorporatingby reference into this prospectus are:

Alldocuments subsequently filed by us with the SEC under Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act (other than current reportson Form 8-K furnished pursuant to Item 2.02 or Item 7.01 of Form 8-K, including any exhibits included with such information, unless otherwiseindicated therein) prior to the termination or completion of the offering made pursuant to this prospectus are also incorporated hereinby reference and will automatically update and supersede information contained or incorporated by reference in this prospectus.

Youmay request a copy of these filings, at no cost, by writing or telephoning us at the following address: 401 Professional Drive, Suite260, Gaithersburg, MD 20879, (240) 430-4212.

WHEREYOU CAN FIND MORE INFORMATION

Wehave filed with the SEC a registration statement on Form S-1 under the Securities Act with respect to the securities offered hereby.This prospectus, which constitutes a part of the registration statement, does not contain all of the information set forth in the registrationstatement or the exhibits and schedules filed therewith. For further information about us and our securities offered hereby, we referyou to the registration statement and the exhibits and schedules filed therewith. Statements contained in this prospectus regarding thecontents of any contract or any other document that is filed as an exhibit to the registration statement are not necessarily complete,and each such statement is qualified in all respects by reference to the full text of such contract or other document filed as an exhibitto the registration statement. The SEC maintains a website that contains reports, proxy and information statements and other informationregarding registrants that file electronically with the SEC. The address is www.sec.gov.

Weare subject to the reporting requirements of the Exchange Act, and file annual, quarterly and current reports, proxy statements and otherinformation with the SEC. You can read our SEC filings, including the registration statement, over the Internet at the SEC’s website.We also maintain a website at www.shuttlepharma.com, at which you may access these materials free of charge as soon as reasonablypracticable after they are electronically filed with, or furnished to, the SEC. The information contained in, or that can be accessedthrough, our website is not part of this prospectus.

PARTII

INFORMATIONNOT REQUIRED IN PROSPECTUS

Item13. Other Expenses of Issuance and Distribution

Thefollowing table provides information regarding the various expenses (other than placement agent fees) payable by us in connection withthe issuance and distribution of the securities being registered hereby. All amounts shown are estimates except the SEC registrationfee.

Item14. Indemnification of Directors and Officers

Section145 of the Delaware General Corporation Law authorizes us to indemnify any director or officer under certain prescribed circumstancesand subject to certain limitations against certain costs and expenses, including attorney’s fees actually and reasonably incurredin connection with any action, suit or proceeding, whether civil, criminal, administrative or investigative, to which a person is partyby reason of being one of our directors or officers if it is determined that such person acted in accordance with the applicable standardof conduct set forth in such statutory provisions. Our certificate of incorporation contains provisions relating to the indemnificationof directors and officers and our by-laws extend such indemnities to the full extent permitted by Delaware law. We currently maintaininsurance for the benefit of any director or officer which cover claims for which we could not indemnify such persons.

Insofaras indemnification for liabilities arising under the Securities Act may be permitted to directors, officers or persons controlling uspursuant to the foregoing provisions, or otherwise, we have been advised that in the opinion of the SEC, such indemnification is againstpublic policy as expressed in the Securities Act and is, therefore, unenforceable.

Item15. Recent Sales of Unregistered Securities

Inthe three years preceding the filing of this registration statement, we sold the following securities that were not registered underthe Securities Act:

OnAugust 1, 2022, in conjunction with entering into three loan agreements for a total of $125,000, which were repayable following consummationof our IPO, we issued warrants to purchase a total of 250 shares at $500 per share. Boustead Securities LLC acted as placement agentand received warrants to purchase 25 shares at $500 per share, equal to 10% of the value of the note offering, and $12,500 in cash compensation.

OnJanuary 11, 2023, we entered into a stock purchase agreement with Alto Opportunity Master Fund, SPC – Segregated Master PortfolioB (“Alto”), pursuant to which we sold to Alto a $4.3 million convertible note and warrant to purchase 5,091 shares of commonstock of the Company, for gross proceeds of $4.0 million. The convertible note amortizes on a monthly basis and the Company can makesuch monthly amortization payments in cash or, subject to certain equity conditions, in registered shares of common stock or a combinationthereof. For equity repayment, the convertible note is convertible into shares of common stock at price per share equal to the lowerof (i) $470, (ii) 90% of the three lowest daily VWAPs of the 15 trading days prior to the payment date or (iii) 90% of the VWAP of thetrading day prior to payment date. The convertible note is repayable over 26 months and bears interest at the rate of 5% per year. Thewarrant is exercisable for four years from the date of closing and is exercisable at $5.53 per share.

InOctober 2024, the Company completed two closing in an up to $1.3 million, 5% original issue discount (“OID”) senior securedconvertible note warrant offering, pursuant to which the Company issued a total of $831,579 of notes and warrants to purchase 13,182shares of common stock, exercisable at a weighted-average price of $35.59 per share. The notes bear interest at the rate of 14.5% peryear, with the interest payable quarterly in cash, mature one year after the date of issuance, are redeemable at any time by the Companyat a 107% premium to the principal value of the notes and, three months after issuance, can be converted at any time by the holder ata 110% premium to the principal value of the note. Of the above investment amount, the Company’s CEO purchased $250,000 of notesand warrants in the offering.

OnJune 20, 2025, we entered into a securities purchase agreement with an accredited investor, for the sale by the Company to the investor,in a private placement, of 21,924 shares of common stock and 1,158,953 pre-funded warrants to purchase shares of common stock, at a purchaseprice of $3.60 per share or $3.599 per pre-funded warrant. The private placement closed on June 24, 2025.

Thepre-funded warrants are immediately exercisable, at a nominal exercise price of $0.001, and may be exercised at any time until all ofthe pre-funded warrants are exercised in full.

WestParkCapital, Inc. (“WestPark”) acted as the placement agent in connection with the private placement pursuant to an engagementagreement between the Company and WestPark, as amended (as amended, the “Engagement Agreement”). Pursuant to the EngagementAgreement, the Company paid WestPark a fee of 4% of the gross proceeds received by the Company in the private placement. The Companyalso reimbursed certain expenses of WestPark.

Inconnection with the foregoing, we relied upon the exemption from registration provided by Section 4(a)(2) under the Securities Act of1933, as amended, for transactions not involving a public offering.

Item16. Exhibits and Financial Statement Schedules.

(a)Exhibits.

+Certainportions of this exhibit have been redacted in accordance with Item 601(b)(10)(iv) because such information (i) is deemed not materialand (ii) is of the type of information that the Company normally treats as private or confidential.

*Filed herewith

(b)Financial statement schedules

Schedulesnot listed above have been omitted because the information required to be set forth therein is not applicable or is shown in the financialstatements or notes thereto.

Item17. Undertakings

Theundersigned registrant hereby undertakes:

(1)To file, during any period in which offers or sales are being made, a post-effective amendment to this Registration Statement:

(i)To include any prospectus required by Section 10(a)(3) of the Securities Act;

(ii)To reflect in the prospectus any facts or events arising after the effective date of the Registration Statement (or the most recent post-effectiveamendment thereof) which individually or in the aggregate, represent a fundamental change in the information set forth in the RegistrationStatement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securitiesoffered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering rangemay be reflected in the form of prospectus filed with the Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volumeand price represent no more than a 20 percent change in the maximum aggregate offering price set forth in the “Calculation of RegistrationFee” table in the effective Registration Statement; and

(iii)To include any material information with respect to the plan of distribution not previously disclosed in the Registration Statement orany material change to such information in the Registration Statement;

provided,however, that paragraphs (1)(i), (1)(ii) and (1)(iii) of this section do not apply if the information required to be included ina post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Commission by the Registrant pursuantto Section 13 or Section 15(d) of the Securities Exchange Act of 1934 that are incorporated by reference in the Registration Statement,or is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.

(2)That, for the purpose of determining any liability under the Securities Act, each such post-effective amendment shall be deemed to bea new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemedto be the initial bona fide offering thereof.

(3)To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at thetermination of the offering.

(4)That, for the purpose of determining liability under the Securities Act to any purchaser:

(A)Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of thedate the filed prospectus was deemed part of and included in the registration statement; and

(B)Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5) or (b)(7) as part of a registration statement in reliance onRule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii) or (x) for the purpose of providing the information requiredby Section 10(a) of the Securities Act shall be deemed to be part of and included in the registration statement as of the earlier ofthe date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offeringdescribed in prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter,such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statementto which the prospectus relates, and the offering of such securities at that time shall be deemed to be the initial bona fide offeringthereof. Provided, however, that no statement made in a registration statement or prospectus that is part of the registrationstatement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that ispart of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede ormodify any statement that was made in the registration statement or prospectus that was part of the registration statement or made inany such document immediately prior to such effective date; and

(5)The undersigned hereby undertakes that, for purposes of determining any liability under the Securities Act, each filing of the registrant’sannual report pursuant to Section 13(a) or Section 15(d) of the Exchange Act of 1934 that is incorporated by reference in the RegistrationStatement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securitiesat that time shall be deemed to be the initial bona fide offering thereof.

(6)Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers, and controllingpersons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that, in the opinion ofthe Securities and Exchange Commission, such indemnification is against public policy as expressed in the Securities Act and is, therefore,unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expensesincurred or paid by a director, officer or controlling person of the registrant in the successful defense of any action, suit or proceeding)is asserted by such director, officer, or controlling person in connection with the securities being registered, the registrant will,unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdictionthe question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by thefinal adjudication of such issue.

SIGNATURES

Pursuantto the requirements of the Securities Act of 1933, the registrant has duly caused this registration statement to be signed on its behalfby the undersigned, thereunto duly authorized, in the City of Gaithersburg, State of Maryland, on August 4, 2025.

Eachperson whose signature appears below constitutes and appoints Christopher Cooper, his true and lawful attorney-in-fact and agent, withfull power of substitution and re-substitution for him and in his name, place and stead, and in any and all capacities, to sign for himand in him name in the capacities indicated below any and all amendments (including post-effective amendments) to this registration statement(or any other registration statement for the same offering that is to be effective upon filing pursuant to Rule 462(b) under the SecuritiesAct of 1933, as amended), and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securitiesand Exchange Commission, granting unto said attorney-in-fact and agent, full power and authority to do and perform each and every actand thing requisite or necessary to be done in and about the premises, as full to all intents and purposes as he might or could do inperson, hereby ratifying and confirming all that said attorney-in-fact and agent, or his substitute or substitutes, may lawfully do orcause to be done by virtue hereof.

Pursuantto the requirements of the Securities Act of 1933, this registration statement has been signed by the following persons in the capacitiesand on the dates indicated.

Exhibit 5.1

August 4, 2025

ShuttlePharmaceuticals Holdings, Inc.

401Professional Drive, Suite 260

Gaithersburg,MD 20879

Re:Common Stock registered under Registration Statement on Form S-1

Ladiesand Gentlemen:

Wehave acted as counsel to Shuttle Pharmaceuticals Holdings, Inc., a Delaware corporation (the “Company”), in connection withthe Company’s registration statement on Form S-1 filed by the Company with the Securities and Exchange Commission (the “Commission”)under the Securities Act of 1933, as amended (the “Securities Act”). The Registration Statement relates to the resale bythe selling stockholder named therein of up to 1,180,877 shares of common stock, consisting of (i) 21,924 outstanding shares (“OutstandingShares”) and (ii) 1,158,953 shares issuable upon exercise of pre-funded warrants (the “Warrant Shares,” and togetherwith the Outstanding Shares, the “Shares”). The Outstanding Shares and pre-funded warrants were issued pursuant to a securitiespurchase agreement (the “Purchase Agreement”) between the Company and the selling stockholder. The Shares are to be resoldby the selling stockholder, as described in the Registration Statement.

Thisopinion is being delivered in accordance with the requirements of Item 601(b)(5) of Regulation S-K under the Securities Act.

Inconnection with this opinion, we have examined originals or copies, certified or otherwise identified to our satisfaction, of the following:

1.Amended and Restated Certificate of Incorporation of the Company, as amended;

2.Amended and Restated Bylaws of the Company;

3.The Purchase Agreement;

4.The Registration Statement; and

5.Written consent of the Board of Directors of the Company approving the Purchase Agreement.

Wehave also examined originals or copies, certified or otherwise identified to our satisfaction, of such records of the Company and suchagreements, certificates and receipts of public officials, certificates of officers or other representatives of the Company and others,and such other documents as we have deemed necessary or appropriate as a basis for the opinions stated below.

1185AVENUE OF THE AMERICAS | 31ST FLOOR | NEW YORK, NY | 10036

T(212) 930-9700 | F (212) 930-9725 | WWW.SRFC.LAW

Inour examination, we have assumed the genuineness of all signatures, including endorsements, the legal capacity and competency of allnatural persons, the authenticity of all documents submitted to us as originals, the conformity to original documents of all documentssubmitted to us as facsimile, electronic, certified or photostatic copies, and the authenticity of the originals of such copies. In makingour examination of executed documents, we have assumed (i) that the parties thereto, other than the Company, had the power, corporateor other, to enter into and perform all obligations thereunder and (ii) the due authorization by all requisite action, corporate or other,and the execution and delivery by such parties of such documents, and the validity and binding effect thereof on such parties.

Theopinion expressed below is limited to the Delaware General Corporation Law and we express no opinion as to the effect on the matterscovered by the laws of any other jurisdiction.

Basedon the foregoing, we are of the opinion that (i) the Outstanding Shares are validly issued, fully paid and non-assessable, and (ii) theWarrant Shares, when issued upon exercise of the pre-funded warrants pursuant to the terms and conditions of the pre-funded warrantswill be validly issued, fully paid and non-assessable.

Wehereby consent to the use of this opinion as Exhibit 5.1 to the Registration Statement, and further consent to the reference to us inthe Registration Statement. In giving such consent, we do not hereby admit that we are within the category of persons whose consent isrequired under Section 7 of the Securities Act or the rules and regulations thereunder.

Verytruly yours,

/s/Sichenzia Ross Ference Carmel LLP

SichenziaRoss Ference Carmel LLP

1185 AVENUE OF THE AMERICAS | 31ST FLOOR | NEW YORK, NY | 10036

T(212) 930-9700 | F (212) 930-9725 | WWW.SRFC.LAW

Exhibit 23.1

Consent of Independent Registered Public Accounting Firm

We consent to the incorporationby reference in this Registration Statement on Form S-1 of Shuttle Pharmaceuticals Holdings, Inc. (the “Company”) of our reportdated February 26, 2025, with respect to the consolidated financial statements of the Company, included in the Annual Report on Form 10-Kfor the year ended December 31, 2024. Our report contains an explanatory paragraph describing the conditions that raise substantial doubtabout the Company’s ability to continue as a going concern in Note 1 to the consolidated financial statements. We also consent tothe reference to our firm under the caption “Experts” in the Registration Statement.

/s/ Forvis Mazars, LLP

Atlanta, Georgia

August 4, 2025