Product Name :
ML323 — USP1-UAF1 Inhibitor
Description:
ML323 is a potent, selective and reversible inhibitor of the USP1-UAF1 deubiquitinase complex with IC50 ~76 nM in the Ub-Rho assay. It has excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases, showed little to no inhibition against other USPs tested, including USP2, USP5, USP7, USP8, USP10, USP11, USP14 and USP21. Inhibition mechanism and HDX studies suggest that ML323 binds away from the USP1 active site. ML323 inhibits the deubiquitination of PCNA and FANCD2. Inhibition of USP1–UAF1 by ML323 impairs homologous recombination and sister chromatid exchange in U2OS cells. Moreover, ML323 potentiates cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells. A notable feature of ML323 is that it simultaneously targets two major DNA damage response pathways (TLS and FA) by inhibiting a common deubiquitinase. USP1-UAF1 could be a key regulator of the DNA damage response and a target for overcoming resistance to the platinum-based anticancer drugs.
CAS:
1572414-83-5
Molecular Weight:
384.48
Formula:
C23H24N6
Chemical Name:
N-(4-(1H-1,2,3-triazol-1-yl)benzyl)-2-(2-isopropylphenyl)-5-methylpyrimidin-4-amine
Smiles :
CC1=CN=C(N=C1NCC1C=CC(=CC=1)N1C=CN=N1)C1=CC=CC=C1C(C)C
InChiKey:
VUIRVWPJNKZOSS-UHFFFAOYSA-N
InChi :
InChI=1S/C23H24N6/c1-16(2)20-6-4-5-7-21(20)23-24-14-17(3)22(27-23)25-15-18-8-10-19(11-9-18)29-13-12-26-28-29/h4-14,16H,15H2,1-3H3,(H,24,25,27)
Purity:
≥98% (or refer to the Certificate of Analysis)
Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition :
Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life:
≥12 months if stored properly.
Stock Solution Storage:
0 – 4 oC for 1 month or refer to the Certificate of Analysis.
Additional information:
ML323 is a potent, selective and reversible inhibitor of the USP1-UAF1 deubiquitinase complex with IC50 ~76 nM in the Ub-Rho assay. It has excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases, showed little to no inhibition against other USPs tested, including USP2, USP5, USP7, USP8, USP10, USP11, USP14 and USP21. Inhibition mechanism and HDX studies suggest that ML323 binds away from the USP1 active site. ML323 inhibits the deubiquitination of PCNA and FANCD2. Inhibition of USP1–UAF1 by ML323 impairs homologous recombination and sister chromatid exchange in U2OS cells. Moreover, ML323 potentiates cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells. A notable feature of ML323 is that it simultaneously targets two major DNA damage response pathways (TLS and FA) by inhibiting a common deubiquitinase.{{Combretastatin A4} medchemexpress|{Combretastatin A4} Cell Cycle/DNA Damage|{Combretastatin A4} Purity & Documentation|{Combretastatin A4} References|{Combretastatin A4} manufacturer|{Combretastatin A4} Cancer} USP1-UAF1 could be a key regulator of the DNA damage response and a target for overcoming resistance to the platinum-based anticancer drugs.{{Sulfapyridine} web|{Sulfapyridine} Bacterial|{Sulfapyridine} Biological Activity|{Sulfapyridine} In Vitro|{Sulfapyridine} manufacturer|{Sulfapyridine} Cancer} |Product information|CAS Number: 1572414-83-5|Molecular Weight: 384.PMID:23829314 48|Formula: C23H24N6|Chemical Name: N-(4-(1H-1,2,3-triazol-1-yl)benzyl)-2-(2-isopropylphenyl)-5-methylpyrimidin-4-amine|Smiles: CC1=CN=C(N=C1NCC1C=CC(=CC=1)N1C=CN=N1)C1=CC=CC=C1C(C)C|InChiKey: VUIRVWPJNKZOSS-UHFFFAOYSA-N|InChi: InChI=1S/C23H24N6/c1-16(2)20-6-4-5-7-21(20)23-24-14-17(3)22(27-23)25-15-18-8-10-19(11-9-18)29-13-12-26-28-29/h4-14,16H,15H2,1-3H3,(H,24,25,27)|Technical Data|Appearance: Solid Power.|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: DMSO up to 50 mM|Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.|Shelf Life: ≥12 months if stored properly.|Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.|Drug Formulation: To be determined.|HS Tariff Code: 382200|How to use|In Vitro:|ML323 was used at 10-30 µM in vitro and cellular assays.|References:|Liang Q, et al. A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses. (2014) Nat Chem Biol. 10(4):298-304.Products are for research use only. Not for human use.|Documents||
