1572414-83-5 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
Check Digit Verification of cas no
The CAS Registry Mumber 1572414-83-5 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,5,7,2,4,1 and 4 respectively; the second part has 2 digits, 8 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 1572414-83:
(9*1)+(8*5)+(7*7)+(6*2)+(5*4)+(4*1)+(3*4)+(2*8)+(1*3)=165
165 % 10 = 5
So 1572414-83-5 is a valid CAS Registry Number.