TAS4464

Chemical Name:

7H-Pyrrolo[2,3-d]pyrimidin-4-amine, 7-[5-[(aminosulfonyl)amino]-5-deoxy-beta-D-ribofuranosyl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]-

SMILES Code: 

NC1=C2C(N([C@H]3[C@@H]([C@@H]([C@@H](CNS(=O)(N)=O)O3)O)O)C=C2C#CC4=C(F)C=CC=C4OCC)=NC=N1

InChi Code:

InChI=1S/C21H23FN6O6S/c1-2-33-14-5-3-4-13(22)12(14)7-6-11-9-28(20-16(11)19(23)25-10-26-20)21-18(30)17(29)15(34-21)8-27-35(24,31)32/h3-5,9-10,15,17-18,21,27,29-30H,2,8H2,1H3,(H2,23,25,26)(H2,24,31,32)/t15-,17-,18-,21-/m1/s1

InChi Key:

TZTRUHFXPVXWRD-QTQZEZTPSA-N

Keyword:

1848959-10-3；CAS:1848959-10-3；CAS：1848959-10-3；TAS4464; TAS-4464; TAS 4464

Solubility: Soluble in DMSO

Storage: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Description: 

TAS4464 is a highly potent and selective inhibitor of NEDD8 (IC50 of 0.955 nM). TAS4464 selectively inhibited NAE relative to the other E1s UAE and SAE. TAS4464 treatment inhibited cullin neddylation and subsequently induced the accumulation of CRL substrates such as CDT1, p27, and phosphorylated IκBα in human cancer cell lines. TAS4464 showed greater inhibitory effects than those of the known NAE inhibitor MLN4924 both in enzyme assay and in cells. Cytotoxicity profiling revealed that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines but also patient derived tumor cells. TAS4464 showed prolonged target inhibition in human tumor xenograft mouse models; weekly or twice a week TAS4464 administration led to prominent antitumor activity in multiple human tumor xenograft mouse models including both hematologic and solid tumors without marked weight loss. As a conclusion, TAS4464 is the most potent and highly selective NAE inhibitor reported to date, showing superior antitumor activity with prolonged target inhibition. It is, therefore, a promising agent for the treatment of a variety of tumors including both hematologic and solid tumors. These results support the clinical evaluation of TAS4464 in hematologic and solid tumors.

Target: Highly selective Nedd8 activator (NAE) inhibitor