ISM5939 + docetaxel

ISM5939 + docetaxel is an experimental **combination therapy** for cancer, consisting of ISM5939, an orally available, highly selective small molecule inhibitor of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and docetaxel, a well-established microtubule inhibitor chemotherapeutic. ISM5939 was developed using generative AI (by Insilico Medicine) and modulates the **cGAS-STING signaling pathway** by inhibiting ENPP1, leading to enhanced antitumor immune responses by preserving cGAMP and boosting immune cell function within the tumor microenvironment[1][2][3][4][5][6]. Preclinical data demonstrate that combining ISM5939 with docetaxel markedly **synergizes to improve tumor growth inhibition** compared to either agent alone, likely via a combination of immunomodulatory (ISM5939) and cytotoxic (docetaxel) mechanisms. Notably, ISM5939 facilitates cGAMP accumulation and increases antitumor immune activity, while docetaxel causes DNA damage and cell cycle arrest in rapidly dividing tumor cells; the combination further increases CD8+ T-cell infiltration, M1 macrophage polarization, and other immunostimulatory effects in solid tumor models[1][2][3]. IND clearance for clinical development of ISM5939 was granted by the FDA in late 2024; as of 2025, combination therapy with docetaxel remains under preclinical and early clinical assessment in solid tumors[4][5][6].

Other names

ISM5939ISM-5939ISM 5939docetaxel