5.31131

USP1-UAF1 Inhibitor, ML323

• 동의어(들): 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
• 실험식(Hill 표기법): C₂₃H₂₄N₆
• CAS Number: 1572414-83-5
• Molecular Weight: 384.48
• UNSPSC 코드: 12352200
• PubChem Substance ID: 60167849
• NACRES: NA.77

속성

• 분석: ≥98% (HPLC)
• Quality Level: 100
• 형태: powder
• 제조업체/상표: Calbiochem^®
• 저장 조건: OK to freeze; protect from light
• 색상: off-white
• solubility: DMSO: 100 mg/mL
• 저장 온도: 2-8°C
• SMILES string: CC1=CN=C(N=C1NCC2=CC=C(C=C2)N3C=CN=N3)C4=CC=CC=C4C(C)C

설명

일반 설명

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.

생화학적/생리학적 작용

Cell permeable: yes

Primary Target
USP1-UAF1 deubiquitinase (DUBs) complex

Reversible: yes

포장

Packaged under inert gas

경고

Toxicity: Standard Handling (A)

재구성

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

기타 정보

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

법적 정보

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

안전성 정보

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable