Shuttle Pharmaceuticals Holdings Inc. American Stock Offering Prospectus (Version as of March 9, 2026)

2,238,800 Shares of Common StockPre-Funded Warrants to purchase up to 4,761,200 Shares of Common Stock We are offering (i) 2,238,800 shares of our common stock, at a public offering price of $0.50 per share of common stock, and (ii) pre-funded warrants to purchase up to 4,761,200 shares of common stock at an offering price of $0.499 per pre-funded warrant, pursuant to this Each pre-funded warrant is exercisable for one share of our common stock. Pre-funded warrants are exercisable upon issuance and willexpire when exercised in full. The exercise price of each pre-funded warrant is $0.001 per share. The pre-funded warrants will not be listed onthe Nasdaq Capital Market and are not expected to trade in any market, however we anticipate that the shares of our common stock to be issued We have engaged E.F. Hutton & Co. (“E.F. Hutton”), or the placement agent, to act as our exclusive placement agent in connection withthis offering. The placement agent has agreed to use its reasonable best efforts to arrange for the sale of the securities offered by thisprospectus. The placement agent is not purchasing or selling any of the securities we are offering and the placement agent is not required toarrange the purchase or sale of any specific number or dollar amount of securities. We have agreed to pay to the placement agent the placementagent fees set forth in the table below, which assumes that we sell all of the securities offered by this prospectus. Further, any proceeds from the Our common stock is listed on the Nasdaq Capital Market under the symbol “SHPH.” The closing price of our common stock on theNasdaq Stock Market on March 5, 2026, was $0.87 per share. There is no established trading market for the pre-funded warrants, and we do not expect a market to develop. We do not intend to applyfor a listing of the pre-funded warrants on any securities exchange or other nationally recognized trading system. Without an active trading Investing in our securities involves a high degree of risk. These risks are described in the “Risk Factors” section on page 5 of thisprospectus. You should also consider the risk factors described or referred to in any documents incorporated by reference in this Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of thesesecurities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense. Delivery of the securities offered hereby is expected to be made on or about March 9, 2026, subject to satisfaction of customary closingconditions. ABOUT THIS PROSPECTUS You should read this prospectus and the related exhibits filed with the Securities and Exchange Commission (the “SEC”), together with theadditional information described under the headings “Where You Can Find More Information” and “Incorporation by Reference” before You should rely only on the information provided in this prospectus or in a prospectus supplement or any free writing prospectuses oramendments thereto. Neither we, nor the placement agent, have authorized anyone else to provide you with different information. If anyoneprovides you with different or inconsistent information, you should not rely on it. You should assume that the information in this prospectus is Neither we, nor the placement agent, are offering to sell or seeking offers to purchase these securities in any jurisdiction where the offer orsale is not permitted. We have not done anything that would permit this offering or possession or distribution of this prospectus in anyjurisdiction where action for that purpose is required, other than in the United States. Persons outside the United States who come into Unless the context otherwise requires, references in this prospectus to “Shuttle Pharma,” “the Company,” “we,” “us” and “our” refer toShuttle Pharmaceuticals Holdings, Inc. Our logo and all product names are our common law trademarks. Solely for convenience, trademarksand tradenames referred to in this prospectus may appear without the ® or ™ symbols, but such references are not intended to indicate in any All share amounts in this prospectus give effect to our 1-for-25 reverse stock split effected on June 16, 2025, unless otherwise indicated. Industry and Market Data This prospectus and the documents incorporated by reference contain estimates, projections and other information concerning our industry,our business, the science of our products and the markets for our products, including data regarding the incidence of certain medical conditionsand the scientific basis of our products. We obtained the industry, science, market and similar data set forth in this prospectus from our internalestimates and research and from academic and industry research, publications, surveys, and studies conducted by third parties. While webelieve that these industry publications and third-party research, surveys and studies are reliable, we have not