USP1-UAF1 Inhibitor, ML323-Calbiochem

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一般描述

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).

生化/生理作用

Cell permeable: yes
Primary Target
USP1-UAF1 deubiquitinase (DUBs) complex
Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重悬

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

其他说明

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

法律信息

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

基本信息

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安全信息