ISM3091 is an orally available and selective small molecule inhibitor of USP1, and demonstrated potential when targeted against a broad range of tumor lineages with HRD backgrounds. In vitro data showed potent anti-proliferation activity of the compound in BRCA-mutant tumor cells with excellent selectivity.

MAT2A is defined as a synthetic lethality target in MTAP-deleted cancers and plays an essential role in producing S-adenosylmethionine (SAM), a molecule involved in cell function and survival. As a potent and selective MAT2A inhibitor, ISM3412 demonstrated excellent drug-likeness with good solubility and permeability, good activity at low doses in animal models, and a favorable safety profile in preclinical studies.

Research indicates that DGKA mediates T-cell dysfunction during anti-PD-1 therapy, playing a role in the development of resistance to PD-1 blockade. ISM4312A is a novel DGKA inhibitor with excellent potency and high selectivity in cancer immunotherapy. The compound enhanced T-cell activity in vitro and showed robust anti-tumor activities with or without anti-PD-1 therapy in vivo. Those data support the further evaluation of ISM4312A as a potential first-in-class DGKA inhibitor both as a single agent and in combination with a checkpoint inhibitor.

CDK12 inhibitors work synergistically with chemotherapy and PARP inhibitors and can be effective in a number of cancer types, including triple negative breast cancer, colorectal cancer, ovarian cancer, and hepatocellular carcinoma. Insilico's novel inhibitor, designed by its Pharma.AI platform, capitalizes on this cancer treatment approach that relies on the induction of the "BRCAness" phenotype.