CGM097

• CAT Number: I001200
• CAS Number: 1313363-54-0
• Molecular Formula: C₃₈H₄₇ClN₄O₄
• Molecular Weight: 659.26
• Purity: ≥95%
• Target: p53
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• InChI: InChI=1S/C38H47ClN4O4/c1-25(2)47-35-22-33-28(20-34(35)46-5)21-36(44)43(38(33)27-8-10-29(39)11-9-27)32-16-14-30(15-17-32)41(4)23-26-6-12-31(13-7-26)42-19-18-40(3)37(45)24-42/h8-11,14-17,20,22,25-26,31,38H,6-7,12-13,18-19,21,23-24H2,1-5H3/t26?,31?,38-/m0/s1
• InChIKey: CLRSLRWKONPSRQ-CPOWQTMSSA-N
• SMILES: CC(C)OC1=C(C=C2CC(=O)N(C(C2=C1)C3=CC=C(C=C3)Cl)C4=CC=C(C=C4)N(C)CC5CCC(CC5)N6CCN(C(=O)C6)C)OC

NVP-CGM097(CGM-097) is a potent and selective MDM2 inhibitor; an orally bioavailable HDM2 antagonist with potential antineoplastic activity.IC50 value:Target: HDM2-p53 interactionUpon oral administration, p53/HDM2 interaction inhibitor CGM097 inhibits the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited, which may result in the restoration of p53 signaling and, thus, the p53-mediated induction of tumor cell apoptosis. HDM2, a zinc finger nuclear phosphoprotein, is a negative regulator of the p53 pathway, often overexpressed in cancer cells and has been implicated in cancer cell proliferation and survival.

Reference

1:The HDM2 (MDM2) Inhibitor NVP-CGM097 Inhibits Tumor cell Proliferation and Shows Additive Effects with 5-Fluorouracil on the p53 – p21 – Rb – E2F1 Cascade in the p53wildtype Neuroendocrine Tumor Cell Line GOT1. Reuther C, Heinzle V, Nölting S, Herterich S, Hahner S, Halilovic E, Jeay S, Wuerthner JU, Aristizabal Prada ET, Spöttl G, Maurer J, Auernhammer CJ.Neuroendocrinology. 2016 Nov 21. [Epub ahead of print] No abstract available. PMID: 27871087 2:Correction: A distinct p53 target gene set predicts for response to the selective p53-HDM2 inhibitor NVP-CGM097. Jeay S, Gaulis S, Ferretti S, Bitter H, Ito M, Valat T, Murakami M, Ruetz S, Guthy DA, Rynn C, Jensen MR, Wiesmann M, Kallen J, Furet P, Gessier F, Holzer P, Masuya K, Würthner J, Halilovic E, Hofmann F, Sellers WR, Graus Porta D.Elife. 2016 Nov 17;5. pii: e19317. doi: 10.7554/eLife.19317. No abstract available. PMID: 27852439 Free PMC Article3:Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors. Holzer P, Masuya K, Furet P, Kallen J, Valat-Stachyra T, Ferretti S, Berghausen J, Bouisset-Leonard M, Buschmann N, Pissot-Soldermann C, Rynn C, Ruetz S, Stutz S, Chène P, Jeay S, Gessier F.J Med Chem. 2015 Aug 27;58(16):6348-58. doi: 10.1021/acs.jmedchem.5b00810. Epub 2015 Aug 5. PMID: 26181851 4:A distinct p53 target gene set predicts for response to the selective p53-HDM2 inhibitor NVP-CGM097. Jeay S, Gaulis S, Ferretti S, Bitter H, Ito M, Valat T, Murakami M, Ruetz S, Guthy DA, Rynn C, Jensen MR, Wiesmann M, Kallen J, Furet P, Gessier F, Holzer P, Masuya K, Würthner J, Halilovic E, Hofmann F, Sellers WR, Graus Porta D.Elife. 2015 May 12;4. doi: 10.7554/eLife.06498. Erratum in: Elife. 2016 Nov 17;5:. PMID: 25965177 Free PMC Article