1572414-83-5

Basic information

• Product Name: ML-323
• Synonyms: ML-323;5-Methyl-2-[2-(1-methylethyl)phenyl]-N-[[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl]-4-pyrimidinamine;4-Pyrimidinamine, 5-methyl-2-[2-(1-methylethyl)phenyl]-N-[[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl]-;5-Methyl-2-[2-(1-methylethyl)phenyl]-N-[[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl]-4-pyrimidinamine ML323;ML323, >=98%;N-(4-(1H-1,2,3-Triazol-1-yl)benzyl)-2-(2-isopropylphenyl)-5-methylpyrimidin-4-amine;ML323, 99%, an USP1-UAF1 inhibitor
• CAS NO: 1572414-83-5
• Molecular Formula: C23H24N6
• Molecular Weight: 384.47686
• Product Categories: Inhibitors
• Mol File: 1572414-83-5.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 515.4±60.0 °C(Predicted)
• Appearance: /
• Density: 1.20±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 40 mg/ml), or in Ethanol (up to 20 mg/ml)
• PKA: 5.37±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: ML-323(CAS DataBase Reference)
• NIST Chemistry Reference: ML-323(1572414-83-5)
• EPA Substance Registry System: ML-323(1572414-83-5)

Safety Data

• Hazardous Substances Data: 1572414-83-5(Hazardous Substances Data)

Usage

Description

ML-323 is a potent and reversible USP1-UAF1 deubiquitinase complex inhibitor with excellent selectivity against human DUBs, deSUMOylase, deneddylase, and unrelated proteases. It has demonstrated the ability to increase levels of monoubiquitinated PCNA in H1299 non-small cell lung cancer cells and potentiate cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells. Additionally, ML-323 has shown to cause replication fork destabilization and decreased viability in BRCA1-deficient tumor cells.

Uses

Used in Pharmaceutical Industry:
ML-323 is used as a USP1-UAF1 inhibitor for its potential in cancer treatment. It has shown to increase the levels of monoubiquitinated PCNA in non-small cell lung cancer cells, which can be beneficial in the development of targeted cancer therapies.
Used in Cancer Research:
ML-323 is used as a research tool for studying the role of USP1-UAF1 deubiquitinase complex in cancer cell replication and survival. Its ability to potentiate cisplatin cytotoxicity and destabilize replication forks in BRCA1-deficient tumor cells makes it a valuable compound for investigating novel cancer treatment strategies.
Used in Drug Development:
ML-323 is used as a lead compound in the development of new drugs targeting the USP1-UAF1 deubiquitinase complex. Its high potency and selectivity make it a promising candidate for further optimization and development into a therapeutic agent for various types of cancer.

in vitro

studies in h596 cells showed that ml-323 blocked the deubiquitination of pcna and fancd2 via suppressing usp1–uaf1 activity. it was reported that ml-323 potently inhibited usp1-uaf1 with ic50 values of 76 nm and 174 nm in ubiquitin-rhodamine (ub-rho) assay and orthogonal gel-based assay, respectively. in addition, by targeting tls and fa, two major dna damage response pathways, ml-323 increased cisplatin cytotoxicity both in nsclc h596 cells and u2os osteosarcoma cells. moreover, this agent exhibited a high selectivity to human dubs, desumoylase, deneddylase and unrelated proteases. [1]

IC 50

ml-323 is a highly potent and selective inhibitor of usp1-uaf1 with ic50 value of 76 nm.

References

1) Dexheimer et al. (2014), Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer; J. Med. Chem., 57 8099 2) Liang et al. (2014), A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses; Nat. Chem. Biol., 10 298 3) Lim et al. (2018) USP1 is required for replication fork protection in BRCA1-deficient tumors; Mol. Cell, 72 925