As filed with the Securities and Exchange Commission on December 11, 2025 Registration No. 333-291628 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 (Amendment No. 1) REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 SHUTTLE PHARMACEUTICALS HOLDINGS, INC. (Exact name of registrant as specified in its charter) David E. Danovitch, Esq. Aaron M. Schleicher, Esq. Sullivan & Worcester LLP 1251 Avenue of the Americas, 19 Floor New York, NY 10020 (212) 660-3060 From time to ...

Core Insights - Shuttle Pharmaceuticals Holdings, Inc. has executed a non-binding letter of intent to acquire Molecule.ai, an AI-driven company focused on transforming drug discovery and development [1][2] - Molecule.ai utilizes advanced machine learning models, including large language models, to enhance the accuracy and efficiency of evaluating novel molecules, thereby shortening development timelines and reducing costs [3][4] - The acquisition aims to integrate Molecule.ai's innovative platform into Shuttle's operations, enhancing its capabilities in drug-target interaction and autonomous drug discovery workflows [5][9] Acquisition Details - Shuttle will acquire all rights and interests of Molecule.ai, assuming all liabilities, with Molecule.ai having no further obligations post-closing [5][7] - The purchase price for the acquisition is set at $10 million, payable in cash and common shares of Shuttle, contingent upon the completion of certain milestones [7] Molecule.ai's Innovations - Molecule.ai's platform includes features such as rapid evaluation of chemical and biological properties, drug-target interaction modeling, and an autonomous framework for drug discovery workflows [9] - The introduction of the Agentic AI mode will enable AI agents to perform multi-step drug discovery processes, significantly reducing manual effort [6][9] Company Missions - Shuttle Pharmaceuticals focuses on improving outcomes for cancer patients undergoing radiation therapy by developing therapies that enhance the effectiveness of radiation while minimizing side effects [10] - Molecule.ai's mission is to empower researchers with next-generation tools that lower costs and improve efficiency in therapeutic development [8]

Core Insights - Shuttle Pharmaceuticals Holdings, Inc. has executed a non-binding letter of intent to acquire Molecule.ai, an AI company focused on transforming drug discovery and development [1][2]. Company Overview - Shuttle Pharmaceuticals is a specialty pharmaceutical company dedicated to improving cancer treatment outcomes, particularly through radiation therapy [10]. - Molecule.ai, founded by Dr. ZT Zhang, utilizes advanced machine learning and large language models to enhance the drug discovery process [8]. Acquisition Details - The acquisition involves Shuttle acquiring all rights and interests of Molecule.ai, assuming its liabilities, and Molecule.ai will have no further obligations post-closing [5]. - The purchase price for Molecule.ai is set at $10 million, payable in cash and common shares of Shuttle, contingent upon the completion of certain milestones [7]. Technological Advancements - Molecule.ai's platform offers capabilities such as rapid evaluation of chemical properties, drug-target interaction modeling, and an autonomous framework for drug discovery workflows [9]. - The introduction of the Agentic AI mode will automate multi-step drug discovery processes, significantly reducing manual efforts [6][9]. Strategic Vision - The collaboration aims to empower scientists with advanced AI tools to enhance drug discovery and expedite the development of new therapies [4].