WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406606
CAS#: 558640-51-0
Description: VER-49009 is a potent HSP90 inhibitor. VER-49009 inhibits Hsp90 with an IC50 value of 47 nM. VER-49009 produces a cellular antiproliferative GI50 value of 685 nM when tested against a human cancer cell line panel. Consistent with inhibition of Hsp90, VER-49009 induces the expression of Hsp27 and Hsp72 while reducing the client proteins C-RAF, B-RAF, survivin, and PRMT5, causing cell cycle arrest and apoptosis.
Hodoodo Cat#: H406606
Name: VER-49009
CAS#: 558640-51-0
Chemical Formula: C19H18ClN3O4
Exact Mass: 387.10
Molecular Weight: 387.820
Elemental Analysis: C, 58.84; H, 4.68; Cl, 9.14; N, 10.84; O, 16.50
Synonym: VER49009; VER 49009; VER-49009
IUPAC/Chemical Name: 3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide
InChi Key: HUNAOTXNHVALTN-UHFFFAOYSA-N
InChi Code: InChI=1S/C19H18ClN3O4/c1-3-21-19(26)18-16(10-4-6-11(27-2)7-5-10)17(22-23-18)12-8-13(20)15(25)9-14(12)24/h4-9,24-25H,3H2,1-2H3,(H,21,26)(H,22,23)
SMILES Code: O=C(C1=C(C2=CC=C(OC)C=C2)C(C3=CC(Cl)=C(O)C=C3O)=NN1)NCC
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | VER-49009 is a Hsp90 inhibitor, with an IC50 of 25 nM and a Kd of 78 nM. |
| In vitro activity: | CFSC cells were treated with various concentrations of VER-49009 (0, 1, 2.5, and 5 μM) for 24 h. The MTT assay revealed that the treatment of CFSC cells with VER-49009 resulted in a significant reduction of cell viability compared with control cells, ranging from 11.06% to 40.74% (P < 0.05) for VER-49009 (Fig. 2a). The toxicity of VER-49009 for CFSC cells was assessed by release of LDH activity (Fig. 2b). At the concentration of 5 μM, VER-49009 was toxic to CFSC cells; however, there was no significant cell damage at lower concentrations (1 or 2.5 μM). Based on these results, VER-49009 at 1 or 2.5 μM inhibits CFSC cell proliferation. Reference: Mol Cell Biochem. 2009 Oct;330(1-2):181-5. https://doi.org/10.1007/s11010-009-0131-4 |
| In vivo activity: | Following administration of four doses of only 4 mg/kg i.p. to athymic mice bearing well-established OVCAR3 human ovarian ascites tumors, VER-49009 induced clear depletion of ERBB2 at 3 and 8 h following the final dose, with client protein levels returning to normal by 24 h (Fig. 5A, top ). Reference: Mol Cancer Ther. 2007 Apr;6(4):1198-211. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17431102 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 257.85 |
The following data is based on the product molecular weight 387.82 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Sharp SY, Prodromou C, Boxall K, Powers MV, Holmes JL, Box G, Matthews TP, Cheung KM, Kalusa A, James K, Hayes A, Hardcastle A, Dymock B, Brough PA, Barril X, Cansfield JE, Wright L, Surgenor A, Foloppe N, Hubbard RE, Aherne W, Pearl L, Jones K, McDonald E, Raynaud F, Eccles S, Drysdale M, Workman P. Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues. Mol Cancer Ther. 2007 Apr;6(4):1198-211. doi: 10.1158/1535-7163.MCT-07-0149. PMID: 17431102. 2. Sun X, Zhang XD, Cheng G, Hu YH, Wang HY. Inhibition of hepatic stellate cell proliferation by heat shock protein 90 inhibitors in vitro. Mol Cell Biochem. 2009 Oct;330(1-2):181-5. doi: 10.1007/s11010-009-0131-4. Epub 2009 May 3. PMID: 19412730. |
| In vivo protocol: | 1. Sharp SY, Prodromou C, Boxall K, Powers MV, Holmes JL, Box G, Matthews TP, Cheung KM, Kalusa A, James K, Hayes A, Hardcastle A, Dymock B, Brough PA, Barril X, Cansfield JE, Wright L, Surgenor A, Foloppe N, Hubbard RE, Aherne W, Pearl L, Jones K, McDonald E, Raynaud F, Eccles S, Drysdale M, Workman P. Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues. Mol Cancer Ther. 2007 Apr;6(4):1198-211. doi: 10.1158/1535-7163.MCT-07-0149. PMID: 17431102. |
1: Jeong CH, Park HB, Jang WJ, Jung SH, Seo YH. Discovery of hybrid Hsp90 inhibitors and their anti-neoplastic effects against gefitinib-resistant non-small cell lung cancer (NSCLC). Bioorg Med Chem Lett. 2014 Jan 1;24(1):224-7. doi: 10.1016/j.bmcl.2013.11.034. Epub 2013 Nov 22. PubMed PMID: 24345447.
2: Sun X, Zhang XD, Cheng G, Hu YH, Wang HY. Inhibition of hepatic stellate cell proliferation by heat shock protein 90 inhibitors in vitro. Mol Cell Biochem. 2009 Oct;330(1-2):181-5. doi: 10.1007/s11010-009-0131-4. Epub 2009 May 3. PubMed PMID: 19412730.
3: Gaspar N, Sharp SY, Pacey S, Jones C, Walton M, Vassal G, Eccles S, Pearson A, Workman P. Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells. Cancer Res. 2009 Mar 1;69(5):1966-75. doi: 10.1158/0008-5472.CAN-08-3131. Epub 2009 Feb 24. Erratum in: Cancer Res. 2009 Apr 15;69(8):3721. PubMed PMID: 19244114; PubMed Central PMCID: PMC2652695.
4: Smith JR, Clarke PA, de Billy E, Workman P. Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitors. Oncogene. 2009 Jan 15;28(2):157-69. doi: 10.1038/onc.2008.380. Epub 2008 Oct 20. PubMed PMID: 18931700; PubMed Central PMCID: PMC2635547.
5: Sharp SY, Prodromou C, Boxall K, Powers MV, Holmes JL, Box G, Matthews TP, Cheung KM, Kalusa A, James K, Hayes A, Hardcastle A, Dymock B, Brough PA, Barril X, Cansfield JE, Wright L, Surgenor A, Foloppe N, Hubbard RE, Aherne W, Pearl L, Jones K, McDonald E, Raynaud F, Eccles S, Drysdale M, Workman P. Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues. Mol Cancer Ther. 2007 Apr;6(4):1198-211. PubMed PMID: 17431102.
6: Barril X, Beswick MC, Collier A, Drysdale MJ, Dymock BW, Fink A, Grant K, Howes R, Jordan AM, Massey A, Surgenor A, Wayne J, Workman P, Wright L. 4-Amino derivatives of the Hsp90 inhibitor CCT018159. Bioorg Med Chem Lett. 2006 May 1;16(9):2543-8. Epub 2006 Feb 9. PubMed PMID: 16480864.
7: Dymock BW, Barril X, Brough PA, Cansfield JE, Massey A, McDonald E, Hubbard RE, Surgenor A, Roughley SD, Webb P, Workman P, Wright L, Drysdale MJ. Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design. J Med Chem. 2005 Jun 30;48(13):4212-5. PubMed PMID: 15974572
