NVP-LCQ195

• CAT Number: I005401
• CAS Number: 902156-99-4
• Molecular Formula: C17H19Cl2N5O4S
• Molecular Weight: 460.33
• Purity: ≥95%
• Synonyms: 4-[(2,6-dichlorobenzoyl)amino]-N-(1-methylsulfonylpiperidin-4-yl)-1H-pyrazole-5-carboxamide
• Target: Cyclin-Dependent Kinases
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 1 nM(CDK5/p25 and CDK5/p35); 2 nM(CDK1/cyclinB and CDK2/cyclinA); 5 nM(CDK2/cyclinE); 42 nM(CDK3/cyclinE)
• InChI: InChI=1S/C17H19Cl2N5O4S/c1-29(27,28)24-7-5-10(6-8-24)21-17(26)15-13(9-20-23-15)22-16(25)14-11(18)3-2-4-12(14)19/h2-4,9-10H,5-8H2,1H3,(H,20,23)(H,21,26)(H,22,25)
• InChIKey: CCUXEBOOTMDSAM-UHFFFAOYSA-N
• SMILES: CS(=O)(=O)N1CCC(CC1)NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl

NVP-LCQ195（Cat No.:I005401）also known as AT9311 or LCQ195, is a small molecule inhibitor that targets CDK1, CDK2, CDK3, and CDK5. It has a potent inhibitory effect on these cyclin-dependent kinases, with IC50 values ranging from 1 to 42 nM. NVP-LCQ195 has been shown to induce G1 phase cell cycle arrest, inhibit cell proliferation, and induce apoptosis in various cancer cell lines. Additionally, NVP-LCQ195 has demonstrated antitumor activity in xenograft models of human cancer, making it a promising candidate for cancer therapy.

Reference

[1]. McMillin DW, Delmore J, Negri J et al. Molecular and cellular effects of multi-targeted cyclin-dependent kinase inhibition in myeloma: biological and clinical implications. Br J Haematol. 2011 Feb;152(4):420-32.
Abstract
Cell cycle regulators, such as cyclin-dependent kinases (CDKs), are appealing targets for multiple myeloma (MM) therapy given the increased proliferative rates of tumour cells in advanced versus early stages of MM. We hypothesized that a multi-targeted CDK inhibitor with a different spectrum of activity compared to existing CDK inhibitors could trigger distinct molecular sequelae with therapeutic implications for MM. We therefore studied the small molecule heterocyclic compound NVP-LCQ195/AT9311 (LCQ195), which inhibits CDK1, CDK2 and CDK5, as well as CDK3 and CDK9. LCQ195 induced cell cycle arrest and eventual apoptotic cell death of MM cells, even at sub-μmol/l concentrations, spared non-malignant cells, and overcame the protection conferred to MM cells by stroma or cytokines of the bone marrow milieu. In MM cells, LCQ195 triggered decreased amplitude of transcriptional signatures associated with oncogenesis, drug resistance and stem cell renewal, including signatures of activation of key transcription factors for MM cells e.g. myc, HIF-1α, IRF4. Bortezomib-treated MM patients whose tumours had high baseline expression of genes suppressed by LCQ195 had significantly shorter progression-free and overall survival than those with low levels of these transcripts in their MM cells. These observations provide insight into the biological relevance of multi-targeted CDK inhibition in MM.