ML-323
- CAS NO.:1572414-83-5
- Empirical Formula: C23H24N6
- Molecular Weight: 384.48
- MDL number: MFCD28099817
- SAFETY DATA SHEET (SDS)
- Update Date: 2023-06-30 15:45:59
What is ML-323?
Description
ML323 (1571424-83-5) is a potent and reversible USP1-UAF1 deubiquitinase complex inhibitor with excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases, IC50=76 nM in a ubiquitin-rhodamine 110 assay.1 In H1299 non-small cell lung cancer cells treatment with ML323 dose dependently and robustly increased levels of monoubiquitinated PCNA compared to untreated cells at concentrations as low as 1 μM.1 It potentiates cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells.2? ML323 inhibition of upregulated USP1 in BRCA1-deficient tumor cells results in replication fork destabilization and decreased viability.3
The Uses of ML-323
ML323 is a highly potent and selective USP1-UAF1 inhibitor.
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]
storage
Store at -20°C
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
Properties of ML-323
Boiling point: | 515.4±60.0 °C(Predicted) |
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) |
form | solid |
pka | 5.37±0.10(Predicted) |
color | White |
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. |
Safety information for ML-323
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 |
GHS Hazard Statements |
H302:Acute toxicity,oral |
Precautionary Statement Codes |
P280:Wear protective gloves/protective clothing/eye protection/face protection. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing. |
Computed Descriptors for ML-323
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