attention.Atpresent,thesmallmoleculeUSP1inhibitorKSQ-4279isthemostadvanced.ItisinphaseIclinical trial.ISM3091hasalsoobtainedtheclinicaltrialapprovalinChinaandtheUnitedStates,andclinicaltrialswillbe carriedoutsoon.Inthispaper,thestructure,regulation,physiologicalfunctionofUSP1,therelationshipbetween USP1andtumorigenesis...
We developed a novel small molecule inhibitor, KSQ-4279, that selectively inhibits USP1 and leads to accumulation of mono-ubiquitinated USP1 substrates such as proliferating nuclear antigen (PCNA). In addition to KSQ-4279's activity in BRCA mutant tumors with known homologous recombination ...
the small molecule USP1 inhibitor, and our first oncology program to reach the clinical stage," said Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine. "We hope to further validate our candidate compound in the multicenter trial, as well as the capabilities...
This series is probably ‘drug-like’ since the 2-cyanopyrimidine warhead, which is known to form reversible covalent bonds with active site cysteine residues [77], has clinical precedent from the Novartis cathepsin K inhibitor dutacatib (AFG495) 17 which reached a Phase I osteoporosis trial [...
Moreover, pimozide, the USP1 inhibitor, reversed the chemotherapy resistance in the relapsed/refractory DLBCL. Overall, this study highlights that targeting USP1 may provide an effective therapeutic strategy for the treatment of DLBCL. Materials and methods Patients and samples A total of 106 newly ...
A promising alternative to proteasome inhibitor is to target the enzymes upstream of proteasome-mediated protein degradation, i.e., the ubiquitin conjugation and deconjugation system, to generate more specific, less toxic therapeutic agents. Deubiquitinases (DUBs) are a class of enzymes that cleave ...
We developed KSQ-4279, a potent, highly selective inhibitor of USP1. KSQ-4279 was active in cells, leading to the accumulation of mono-ubiquitinated substrates of USP1 and inhibited the proliferation of cancer cell lines with BRCA mutations or other HRD alterations. Studies investigating the ...