ML-323

SKU: orb1226088

Description

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.

Key Properties

• CAS Number: 1572414-83-5
• MW: 384.4769
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₄N₆
• SMILES: CC1=CN=C(C2=CC=CC=C2C(C)C)N=C1NCC3=CC=C(N4N=NC=C4)C=C3
• Target: DUB
• Solubility: DMSO: ≥ 49 mg/mL

Bioactivity

• In Vitro:
  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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ML323 | ML 323

Quick Database Links

Gene Symbol

DUB