NVP-2

• CAT Number: I020454
• CAS Number: 1263373-43-8
• Molecular Formula: C₂₇H₃₇ClN₆O₂
• Molecular Weight: 513.07
• Purity: ≥95%
• IUPAC Name: 4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]pyridin-4-yl]pyridin-2-yl]amino]methyl]oxane-4-carbonitrile
• InChI: InChI=1S/C27H37ClN6O2/c1-19(16-35-2)32-20-6-8-21(9-7-20)33-26-14-22(23(28)15-30-26)24-4-3-5-25(34-24)31-18-27(17-29)10-12-36-13-11-27/h3-5,14-15,19-21,32H,6-13,16,18H2,1-2H3,(H,30,33)(H,31,34)/t19-,20?,21?/m1/s1
• InChIKey: XWQVQSXLXAXOPJ-QNGMFEMESA-N
• SMILES: C[C@H](COC)NC1CCC(CC1)NC2=NC=C(C(=C2)C3=NC(=CC=C3)NCC4(CCOCC4)C#N)Cl

NVP-2 (Cat N.:I020454) is a potent and selective ATP-competitive inhibitor of cyclin-dependent kinase 9 (CDK9), with an IC50 of 0.514 nM. It also exhibits inhibitory effects on CDK1/CycB, CDK2/CycA, and CDK16/CycY kinases. NVP-2 has shown anti-proliferative activity in leukemia cells, with varying IC50 values across different cell lines. It induces cell apoptosis and engages CDK9 in both wildtype and CRBN−/− MOLT4 cells. Additionally, NVP-2 exhibits CRBN-dependent anti-proliferative and pro-apoptotic effects in MOLT4 cells. Treatment with NVP-2 induces cell apoptosis and upregulates caspase-3 and γH2A.X expression. These findings suggest the potential of NVP-2 as a therapeutic agent for leukemia and highlight its selective inhibition of CDK9 activity.

Reference

[1]. Winter GE, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment.Mol Cell. 2017 Jul 6;67(1):5-18.e19.