5.31131

USP1-UAF1 Inhibitor, ML323

• Sinonimo/i: USP1-UAF1 Inhibitor, ML323, N-(4-(1H-1,2,3-Triazol-1-yl)benzyl)-2-(2-isopropylphenyl)-5-methylpyrimidin-4-amine, USP1–UAF1 Deubiquitinase complex Inhibitor, ML 323
• Formula empirica (notazione di Hill): C₂₃H₂₄N₆
• Numero CAS: 1572414-83-5
• Peso molecolare: 384.48
• Numero MDL: MFCD28099817
• Codice UNSPSC: 12352200
• ID PubChem: 60167849
• NACRES: NA.77

Proprietà

• Saggio: ≥98% (HPLC)
• Livello qualitativo: 100
• Stato: powder
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: off-white
• Solubilità: DMSO: 100 mg/mL
• Temperatura di conservazione: 2-8°C
• Stringa SMILE: CC1=CN=C(N=C1NCC2=CC=C(C=C2)N3C=CN=N3)C4=CC=CC=C4C(C)C
• InChI: 1S/C23H24N6/c1-16(2)20-6-4-5-7-21(20)23-24-14-17(3)22(27-23)25-15-18-8-10-19(11-9-18)29-13-12-26-28-29/h4-14,16H,15H2,1-3H3,(H,24,25,27)

Descrizione

Descrizione generale

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).

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.

Azioni biochim/fisiol

Cell permeable: yes

Primary Target
USP1-UAF1 deubiquitinase (DUBs) complex

Reversible: yes

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Standard Handling (A)

Ricostituzione

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

Altre note

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

Note legali

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

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 11 - Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 3
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable