ML-323

Research use only, not for human use.

A potent, selective, reversible inhibitor of the USP1/UAF1 deubiquitinase complex with IC50 of 76 nM.

A potent, selective, reversible inhibitor of the USP1/UAF1 deubiquitinase complex with IC50 of 76 nM; displays >1,500-fold selectivity versus USP2, USP5, USP7, USP8, and USP46/UAF1; potentiates the cytotoxicity of cisplatin and increases endogenous monoubiquitination levels of both PCNA and FANCD2, two known cellular targets of USP1/UAF1; possesses a promising in vitro ADME profile.

ML-323 (ML323) is a highly potent inhibitor of the USP1-UAF1 deubiquitinase complex with excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases. ML-323 is a potent USP1-UAF1 inhibitor with IC50 values of 76 nM in a ubiquitin-rhodamine (Ub-Rho) assay and 174 nM and 820 nM in orthogonal gel-based assays using K63-linked diubiquitin (di-Ub) and monoubiquitinated PCNA (Ub-PCNA) as substrates, respectively. ML-323 probably exerts its inhibitory effect through an allosteric mechanism. The measured inhibition constants of ML-323 for the free enzyme (Ki) and the enzyme-substrate complex (K’i) are 68 nM and 183 nM. Besides, ML-323 potentiates Cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells. ML-323 (ML323), a probe molecule that displays reversible, nanomolar inhibitory activity and excellent selectivity toward USP1/UAF1. In addition, ML-323 potentiates the cytotoxicity of Cisplatin and increases endogenous monoubiquitination levels of both PCNA and FANCD2, two known cellular targets of USP1/UAF1.

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ML323 | ML 323

Proteasome/Ubiquitin

DUB

USP1-UAF1

Cancer

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1572414-83-5

384.4769

C23H24N6

>98% (HPLC)

DMSO: ≥ 49 mg/mL

CC1=CN=C(C2=CC=CC=C2C(C)C)N=C1NCC3=CC=C(N4N=NC=C4)C=C3

N-(4-(1H-1,2,3-triazol-1-yl)benzyl)-2-(2-isopropylphenyl)-5-methylpyrimidin-4-amine

(-20℃)

With Ice Pack

≥ 2 years