4-(6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-((1r,4r)-4-hyd
SNX-2112 (PF-04928473)
CAS: 908112-43-6
Molecular Formula: C23H27F3N4O3
4-(6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-((1r,4r)-4-hyd - Names and Identifiers
4-(6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-((1r,4r)-4-hyd - Physico-chemical Properties
| Molecular Formula | C23H27F3N4O3 |
| Molar Mass | 464.48 |
| Density | 1.47 |
| Melting Point | 265-266℃ |
| Solubility | DMSO : 25 mg/mL (53.82 mM; Need ultrasonic) |
| Storage Condition | -20℃ |
| Use | SNX-2112 (PF 04928473) is an orally acceptable Hsp90 inhibitor with Kd value of 16 nM and IC50 value of 30 nM for Hsp90 α and Hsp90β. At the same time, it can induce the degradation of Her-2 and inhibit the activities of Grp94 and Trap-1, with IC50 values of 10 nM,4.275 μM and 0.862 μM respectively. SNX-2112 (PF 04928473) combined with Hsp90 subtypes Hsp90α, Hsp90β and Hsp90b1/Grp94,Kd were 4 nM, 6 nM and 484 nM, respectively. |
| In vitro study | Treatment of SNX-2112 cells with 1 μmol/L BT-474 resulted in downregulation of HER2 expression during 3 to 6 hours of treatment, whereas treatment for 10 hours resulted in almost complete loss of HER2 expression. SNX-2112 treatment also resulted in a decrease in total Akt expression. SNX-2112 inhibits cell proliferation by acting on BT474, SKBR-3, SKOV-3, MDA-468, MCF-7 and H1650 cancer cells with an IC50 of 10 to 50 nM. These anti-proliferative effects are associated with low phosphorylation of Rb, G1 phase arrest, and moderate regulatory levels of apoptosis. SNX-2112 competitively binds to the N-terminal ATP binding site of HSP90. SNX-2112 induces apoptosis by caspase-8, -9,-3, and PARP cleavage. SNX-2112 inhibits growth factor-induced Akt and extracellular signal-related kinase (ERK) activation and also overcomes interleukin (IL-6), insulin-like growth factor -1, and bone marrow stromal cell-induced growth advantage. SNX-2112 inhibits human umbilical vein endothelial cell tube formation by abrogating the eNOS/Akt pathway and also significantly inhibits osteoclast formation by down-regulating ERK/c-fos and PU.1. Cell lines (8 cell lines from osteosarcoma, neuroblastoma, hepatoblastoma, and lymphoma) were studied for sensitivity to SNX-2112 with an IC50 of 10-100 μm. The high dose (70 μnm) resulted in longer inhibition, with sub-G1 accumulating more. A significant decrease in the levels of AKT1 and C- Raf was observed with increased cleavage of PARP. Recent studies have shown that NX-2112 induce autophagy by inhibiting Akt/mTOR/p70S6K in a time-and dose-dependent manner. SNX-2112 acts on human melanoma A- 375 cells, significantly inducing apoptosis and autophagy, indicating that SNX-2112 can be used as an effective targeted therapeutic agent. |
| In vivo study | SNX-2112 is a prodrug of SNX-5422, SNX-5422 inhibits the growth of MM cells, prolongs the lifespan of the transplanted tumor mouse model, and inhibits Hsp90, while SNX-2112 does not inhibit the growth of MM cells, but plays a role in the bone marrow microenvironment to block blood vessel growth and osteoclast formation. |
4-(6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-((1r,4r)-4-hyd - Reference
| Reference Show more | 1: Liu KS, Liu H, Qi JH, Liu QY, Liu Z, Xia M, Xing GW, Wang SX, Wang YF. SNX-2112, an Hsp90 inhibitor, induces apoptosis and autophagy via degradation of Hsp90 client proteins in human melanoma A-375 cells. Cancer Lett. 2011 Dec 17. [Epub ahead of print] PubMed PMID: 22182451. 2: Wang SX, Ju HQ, Liu KS, Zhang JX, Wang X, Xiang YF, Wang R, Liu JY, Liu QY, Xia M, Xing GW, Liu Z, Wang YF. SNX-2112, a novel Hsp90 inhibitor, induces G2/M cell cycle arrest and apoptosis in MCF-7 cells. Biosci Biotechnol Biochem. 2011;75(8):1540-5. Epub 2011 Aug 7. PubMed PMID: 21821931. 3: Chinn DC, Holland WS, Yoon JM, Zwerdling T, Mack PC. Anti-tumor activity of the HSP90 inhibitor SNX-2112 in pediatric cancer cell lines. Pediatr Blood Cancer. 2011 Jul 27. doi: 10.1002/pbc.23270. [Epub ahead of print] PubMed PMID: 21796766. 4: Zhai QQ, Gong GQ, Liu Z, Luo Y, Xia M, Xing GW, You XF, Wang YF. Preclinical pharmacokinetic analysis of SNX-2112, a novel Hsp90 inhibitor, in rats. Biomed Pharmacother. 2011 Mar;65(2):132-6. Epub 2010 Dec 30. PubMed PMID: 21227627. 5: Bachleitner-Hofmann T, Sun MY, Chen CT, Liska D, Zeng Z, Viale A, Olshen AB, Mittlboeck M, Christensen JG, Rosen N, Solit DB, Weiser MR. Antitumor activity of SNX-2112, a synthetic heat shock protein-90 inhibitor, in MET-amplified tumor cells with or without resistance to selective MET Inhibition. Clin Cancer Res. 2011 Jan 1;17(1):122-33. PubMed PMID: 21208906; PubMed Central PMCID: PMC3263825. |
4-(6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-((1r,4r)-4-hyd - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.153 ml | 10.765 ml | 21.529 ml |
| 5 mM | 0.431 ml | 2.153 ml | 4.306 ml |
| 10 mM | 0.215 ml | 1.076 ml | 2.153 ml |
| 5 mM | 0.043 ml | 0.215 ml | 0.431 ml |
Last Update：2024-01-02 23:10:35
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Product Name: SNX-2112 (PF-04928473) Visit Supplier Webpage Request for quotationCAS: 908112-43-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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