USP1-IN-9

USP1-IN-9 (Compound 1m) is reversible and noncompetitive ubiquitin-specific proteases (USP1) inhibitors with an IC50 of 8.8 nM, which is designed and synthesized to pyrido[2,3-d]pyrimidin-7(8H)-one derivative based on the disclosed structure of ML323(HY-17543) and KSQ-4279(HY-145471). USP1-IN-9 displays excellent USP1/UAF inhibition and exhibits strong antiproliferation effect in breast cancer cells. USP1-IN-9 can generate enhanced cell killing with PARP inhibitor olaparib(HY-10162) in olaparib-resistant MDA-MB-436/OP cells, which is promising for research in the field of cancer[1].

[1][1] Li H, et al. Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors[j]. Eur J Med Chem. 2024 Jun 14;275:116568.https://pubmed.ncbi.nlm.nih.gov/38889606/|[2][1] Li H, et al. Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors[j]. Eur J Med Chem. 2024 Jun 14;275:116568.https://pubmed.ncbi.nlm.nih.gov/38889606/|[3][1] Li H, et al. Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors[J]. Eur J Med Chem. 2024 Jun 14;275:116568.https://pubmed.ncbi.nlm.nih.gov/38889606/|[4]Li H, et al. Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors[J]. Eur J Med Chem. 2024 Jun 14;275:116568.|[5]Li H, et al. Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors[J]. Eur J Med Chem. 2024 Jun 14;275:116568.