908112-43-6
908112-43-6 structure
- Name: SNX-2112(PF-04928473)
- Chemical Name: pf-04928473
- CAS Number: 908112-43-6
- Molecular Formula: C23H27F3N4O3
- Molecular Weight: 464.481
- Catalog: Biochemical Inhibitor Cytoskeletal Signaling HSP eg HSP90 inhibitor
- Create Date: 2016-10-20 04:42:09
- Modify Date: 2024-01-02 12:02:58
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SNX-2112 is an orally active Hsp90 inhibitor, with a Kd of 16 nM for Hsp90 and IC50s of 30 nM, 30 nM for Hsp90 α and Hsp90 β, also induces Her-2 degradation, and inhibits Grp94 and Trap-1, with IC50s of 10 nM, 4.275 μM and 0.862 μM, respectively.
| Name | pf-04928473 |
|---|---|
| Synonyms |
4-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-((4-hydroxycyclohexyl)amino)benzamide
4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]-2-[(4-hydroxycyclohexyl)amino]benzamide Benzamide, 2-[(4-hydroxycyclohexyl)amino]-4-[4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-3-(trifluoromethyl)-1H-indazol-1-yl]- SNX-2112 4-[6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]-2-[(4-hydroxycyclohexyl)amino]benzamide |
| Description | SNX-2112 is an orally active Hsp90 inhibitor, with a Kd of 16 nM for Hsp90 and IC50s of 30 nM, 30 nM for Hsp90 α and Hsp90 β, also induces Her-2 degradation, and inhibits Grp94 and Trap-1, with IC50s of 10 nM, 4.275 μM and 0.862 μM, respectively. |
|---|---|
| Related Catalog | |
| Target |
HSP90α:30 nM (IC50) HSP90β:30 nM (IC50) GRP94:4275 nM (IC50) TRAP-1:862 nM (IC50) |
| In Vitro | SNX-2112 is an orally active Hsp90 inhibitor, with a Kd of 16 nM, and also induces Her-2 degradation, with an IC50 of 10 nM[1]. SNX-2112 binds to Hsp90, with IC50s of 30 nM, 30 nM, 4.275 μM and 0.862 μM for Hsp90 α and β, Grp94 and Trap-1, respectively[2]. SNX-2112 shows potent antiproliferative activity against various cancer cell types, with IC50s of 3 nM to 53 nM. SNX-2112 exhibits potent effects on Her2 and p-ERK stability in AU565 cells and p-S6 in A375 cells, with IC50s of 11 ± 5, 41 ± 12, and 1 ± 0.6 nM, respectively. SNX-2112 also induces Hsp70 in A375 cells with an IC50 of 2 ± 0.9 nM[1]. In addition, SNX-2112 potently blocks signaling of Hsp90 clients, such as Akt, ERK, and NF-κB pathways in different cells. SNX-2112 inhibits multiple myeloma (MM) cell growth, including MM.1S, U266, INA-6, RPMI8226, OPM1, OPM2, MM.1R, and Dox40 MM cell lines, with IC50s of 52, 55, 19, 186, 89, 67, 93, and 53 nM at 48 hours, respectively. SNX-2112 (2.5-10 nM) also suppresses osteoclast formation, associated with down-regulation of ERK/c-fos and PU.1[3]. |
| Kinase Assay | Briefly, Hsp90 from porcine spleen extract is isolated by affinity capture on a purine-affinity media. The Hsp90 loaded media is then challenged with test compound (SNX-2112) at a given concentration, ranging from 0.8 to 500 μM, and the amount of Hsp90 liberated at each concentration is determined. The resulting IC50 values are corrected for the ATP ligand concentration and presented as apparent Kd values[1]. |
| Cell Assay | To measure proliferation of multiple myeloma (MM) cells and bone marrow stromal cells (BMSCs), the rate of DNA synthesis is measured. MM cells are incubated in 96-well culture plates in the presence of SNX-2112 and/or IL-6 or IGF-1 or BMSCs for 48 hours. Cells are pulsed with 0.5 μCi/well of [3H]-thymidine during the last 8 hours of culture, harvested onto glass filters with an automatic cell harvester, and counted using the LKB Betaplate scintillation counter. Inhibition of proliferation by test compounds (SNX-2112) in solid tumor cell lines is measured in 96-well plates after 72 hours of treatment with Cyquant DNA binding dye. AML, LCL, and K562 cell line proliferation rates are measured after 72 hours of compound treatment with CellTiter-Glo[3]. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Boiling Point | 619.8±55.0 °C at 760 mmHg |
| Melting Point | 265-266℃ |
| Molecular Formula | C23H27F3N4O3 |
| Molecular Weight | 464.481 |
| Flash Point | 328.6±31.5 °C |
| Exact Mass | 464.203522 |
| PSA | 110.24000 |
| LogP | 3.49 |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.638 |
| Storage condition | -20℃ |