SNX-2112

• CAT Number: R039776
• CAS Number: 908112-43-6
• Molecular Formula: C23H27F3N4O3
• Molecular Weight: 464.5
• Purity: ≥95%
• Synonyms: 4-(6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl)-2-((1r,4r)-4-hydroxycyclohexylamino)benzamide; PF 04928473
• Target: HSP
• Solubility: >23.05mg/mL in DMSO
• Storage: 3 years -20C powder
• InChI: InChI=1S/C23H27F3N4O3/c1-22(2)10-17-19(18(32)11-22)20(23(24,25)26)29-30(17)13-5-8-15(21(27)33)16(9-13)28-12-3-6-14(31)7-4-12/h5,8-9,12,14,28,31H,3-4,6-7,10-11H2,1-2H3,(H2,27,33)/t12-,14-
• InChIKey: ZFVRYNYOPQZKDG-MQMHXKEQSA-N
• SMILES: NC(C1=CC=C(N2N=C(C(F)(F)F)C3=C2CC(C)(C)CC3=O)C=C1N[C@@H]4CC[C@@H](O)CC4)=O

SNX-2112, also known as PF 04928473, is an Hsp90 inhibitor which is currently undergoing multiple phase 1 clinical trials. In all cell lines, SNX-2112 led to degradation of MET, HER-2, EGFR, and AKT as well as abrogation of Ras/Raf/MEK/MAPK and PI3K/AKT signaling, followed by complete cell cycle arrest.

Reference

1:Effect of SNX-2112 on proliferation of esophageal cancer cells via regulation of excision repair cross-complementing 1, epidermal growth factor receptor, and p53 expression. Li CY, Ren YJ, Li YD.Genet Mol Res. 2016 Jun 24;15(2). doi: 10.4238/gmr.15028318. PMID: 27420968 Free Article2:Chitosan-functionalised single-walled carbon nanotube-mediated drug delivery of SNX-2112 in cancer cells. Zheng L, Wu S, Tan L, Tan H, Yu B.J Biomater Appl. 2016 Sep;31(3):379-86. doi: 10.1177/0885328216651183. Epub 2016 May 26. PMID: 27231263 3:Phospholipid-stabilized mesoporous carbon nanospheres as versatile carriers for systemic delivery of amphiphobic SNX-2112 (a Hsp90 inhibitor) with enhanced antitumor effect. Zhang X, Zhang T, Ye Y, Chen H, Sun H, Zhou X, Ma Z, Wu B.Eur J Pharm Biopharm. 2015 Aug;94:30-41. doi: 10.1016/j.ejpb.2015.04.023. Epub 2015 May 1. PMID: 25936860 4:Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112. Dong D, Wang X, Wang H, Zhang X, Wang Y, Wu B.Int J Nanomedicine. 2015 Mar 31;10:2521-35. doi: 10.2147/IJN.S79734. eCollection 2015. PMID: 25848269 Free PMC Article5:Comparative effects of SNX-7081 and SNX-2112 on cell cycle, apoptosis and Hsp90 client proteins in human cancer cells. Wang X, Wang S, Liu Y, Huang D, Zheng K, Zhang Y, Wang X, Liu Q, Yang D, Wang Y.Oncol Rep. 2015 Jan;33(1):230-8. doi: 10.3892/or.2014.3552. Epub 2014 Oct 20. PMID: 25334086 6:Combination of SNX-2112 with 5-FU exhibits antagonistic effect in esophageal cancer cells. Liu Y, Wang X, Wang Y, Zhang Y, Zheng K, Yan H, Zhang L, Chen W, Wang X, Liu Q, Wang S, Wang Y.Int J Oncol. 2015 Jan;46(1):299-307. doi: 10.3892/ijo.2014.2714. Epub 2014 Oct 20. PMID: 25333998 7:The Hsp90 inhibitor SNX-2112 induces apoptosis of human hepatocellular carcinoma cells: the role of ER stress. Wang X, Wang S, Liu Y, Ding W, Zheng K, Xiang Y, Liu K, Wang D, Zeng Y, Xia M, Yang D, Wang Y.Biochem Biophys Res Commun. 2014 Mar 28;446(1):160-6. doi: 10.1016/j.bbrc.2014.02.081. Epub 2014 Feb 25. PMID: 24582562 8:P-glycoprotein (P-gp)-mediated efflux limits intestinal absorption of the Hsp90 inhibitor SNX-2112 in rats. Liu H, Sun H, Wu Z, Zhang X, Wu B.Xenobiotica. 2014 Aug;44(8):763-8. doi: 10.3109/00498254.2014.891781. Epub 2014 Feb 20. PMID: 24555822 9:Metabolite elucidation of the Hsp90 inhibitor SNX-2112 using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). Liu W, Liu H, Sun H, Dong D, Ma Z, Wang Y, Wu B.Xenobiotica. 2014 May;44(5):455-64. doi: 10.3109/00498254.2013.853849. Epub 2013 Nov 5. PMID: 24191862 10:The Hsp90 inhibitor SNX-2112, induces apoptosis in multidrug resistant K562/ADR cells through suppression of Akt/NF-κB and disruption of mitochondria-dependent pathways. Wang R, Shao F, Liu Z, Zhang J, Wang S, Liu J, Liu H, Chen H, Liu K, Xia M, Wang Y.Chem Biol Interact. 2013 Sep 5;205(1):1-10. doi: 10.1016/j.cbi.2013.06.007. Epub 2013 Jun 15. PMID: 23777986