5311310001 USP1-UAF1 Inhibitor; ML323 1PC X 10MG

Biochem/physiol Actions

Reversible: yes

Primary TargetUSP1-UAF1 deubiquitinase (DUBs) complex

Cell permeable: yes

General description

A cell-permeable, non-toxic triazolylbenzyl-pyrimidinamine compound that acts as a highly selective, potent, and reversible inhibitor of ubiquitin-specific protease 1 (USP1)-USP1 associated factor 1 (UAF1) deubiquitinase (DUB) (IC₅₀ = 76, 174, and 820 nM in Ub-Rhodamine; K63 linked diubiquitin; and Ub-PCNA substrate based assays) without disrupting USP1-UAF1 association. The inhibition appears to be allosteric in nature with inhibition constants of 68 nM and 183 nM (for free enzyme and enzyme-substrate complex, respectively). Displays excellent selectivity over 18-DUBs including USP1 and USP46-UAF1, related deSUMOylases & deneddylases, 70 unrelated proteases, and 451 kinases. Effectively sensitizes cisplatin-resistant NSCLC H596 cells and U2OS osteosarcoma cells to cisplatin (Cat. No. 232120) and blocks cell cycle at the S phase (EC₅₀ = 171 and 59 nM for 1:1 and 1:4 ratio of cisplatin to ML323 in H596 cells).Please note that the molecular weight for this compound is batch-specific due to variable water content.

A cell-permeable, non-toxic triazolylbenzyl-pyrimidinamine compound that acts as a highly selective, potent, and reversible inhibitor of ubiquitin-specific protease 1 (USP1)-USP1 associated factor 1 (UAF1) deubiquitinase (DUB) (IC₅₀ = 76, 174, and 820 nM in Ub-Rhodamine; K63 linked diubiquitin; and Ub-PCNA substrate based assays) without disrupting USP1-UAF1 association. The inhibition appears to be allosteric in nature with inhibition constants of 68 nM and 183 nM (for free enzyme and enzyme-substrate complex, respectively). Displays excellent selectivity over 18-DUBs including USP1 and USP46-UAF1, related deSUMOylases & deneddylases, 70 unrelated proteases, and 451 kinases. Effectively sensitizes cisplatin-resistant NSCLC H596 cells and U2OS osteosarcoma cells to cisplatin (Cat. No. 232120) and blocks cell cycle at the S phase (EC₅₀ = 171 and 59 nM for 1:1 and 1:4 ratio of cisplatin to ML323 in H596 cells).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Dexheimer, T.S., et al. 2014. J. Med. Chem.57, in press.Liang, Q., et al. 2014. Nat Chem Biol.10, 298.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Standard Handling (A)