USP1-UAF1 Inhibitor, ML323-Calbiochem

C₂₃H₂₄N₆

384.48

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).

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

Toxicity: Standard Handling (A)

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

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

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

100

≥98% (HPLC)

powder

Calbiochem^®

OK to freeze
protect from light

off-white

DMSO: 100 mg/mL

2-8℃

Packaged under inert gas

11 - Combustible Solids

WGK 3