PF-04929113 mesylate
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MedKoo CAT#: 206835

CAS#: 1173111-67-5 (mesylate)

Description: PF-04929113, also known as SNX-5422; is a synthetic prodrug targeting the human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Although the mechanism of action remains to be fully elucidated, Hsp90 inhibitor SNX-5542 is rapidly converted to SNX-2112, which accumulates in tumors relative to normal tissues. SNX-2112 inhibits Hsp90, which may result in the proteasomal degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation.


Price and Availability

Size
Price

50mg
USD 450
500mg
USD 2450
5g
USD 7450
Size
Price

100mg
USD 850
1g
USD 3450
Size
Price

200mg
USD 1450
2g
USD 4950

PF-04929113 mesylate, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206835
Name: PF-04929113 mesylate
CAS#: 1173111-67-5 (mesylate)
Chemical Formula: C26H34F3N5O7S
Exact Mass:
Molecular Weight: 617.6412
Elemental Analysis: C, 50.56; H, 5.55; F, 9.23; N, 11.34; O, 18.13; S, 5.19


Related CAS #: 908115-27-5 (free base)   1173111-67-5 (mesylate 1:1)    

Synonym: PF-04929113 mesylate; SNX5422; SNX-5422; SNX 5422; PF4929113; PF-4929113; PF 4929113; PF04929113; PF 04929113; PF-04929113.

IUPAC/Chemical Name: (1r,4r)-4-((2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenyl)amino)cyclohexyl glycinate mesylate

InChi Key: NVGFSTMGRRADRG-IOJSEOPQSA-N

InChi Code: InChI=1S/C25H30F3N5O4.CH4O3S/c1-24(2)10-18-21(19(34)11-24)22(25(26,27)28)32-33(18)14-5-8-16(23(30)36)17(9-14)31-13-3-6-15(7-4-13)37-20(35)12-29;1-5(2,3)4/h5,8-9,13,15,31H,3-4,6-7,10-12,29H2,1-2H3,(H2,30,36);1H3,(H,2,3,4)/t13-,15-;

SMILES Code: OS(=O)(C)=O.NCC(O[C@H]1CC[C@H](NC2=CC(N3N=C(C(F)(F)F)C4=C3CC(C)(C)CC4=O)=CC=C2C(N)=O)CC1)=O


Technical Data

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

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).

Harmonized System Code:
293490


References

1: Kim SH, Kang JG, Kim CS, Ihm SH, Choi MG, Yoo HJ, Lee SJ. The heat shock protein 90 inhibitor SNX5422 has a synergistic activity with histone deacetylase inhibitors in induction of death of anaplastic thyroid carcinoma cells. Endocrine. 2016 Feb;51(2):274-82. doi: 10.1007/s12020-015-0706-7. Epub 2015 Jul 29. PubMed PMID: 26219406.

2: Dunna NR, Bandaru S, Akare UR, Rajadhyax S, Gutlapalli VR, Yadav M, Nayarisseri A. Multiclass comparative virtual screening to identify novel Hsp90 inhibitors: a therapeutic breast cancer drug target. Curr Top Med Chem. 2015;15(1):57-64. PubMed PMID: 25579569.

3: Infante JR, Weiss GJ, Jones S, Tibes R, Bauer TM, Bendell JC, Hinson JM Jr, Von Hoff DD, Burris HA 3rd, Orlemans EO, Ramanathan RK. Phase I dose-escalation studies of SNX-5422, an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumours. Eur J Cancer. 2014 Nov;50(17):2897-904. doi: 10.1016/j.ejca.2014.07.017. Epub 2014 Sep 25. PubMed PMID: 25262379.

4: Debnath A, Shahinas D, Bryant C, Hirata K, Miyamoto Y, Hwang G, Gut J, Renslo AR, Pillai DR, Eckmann L, Reed SL, McKerrow JH. Hsp90 inhibitors as new leads to target parasitic diarrheal diseases. Antimicrob Agents Chemother. 2014 Jul;58(7):4138-44. doi: 10.1128/AAC.02576-14. Epub 2014 May 12. PubMed PMID: 24820073; PubMed Central PMCID: PMC4068574.

5: Lamoureux F, Thomas C, Yin MJ, Fazli L, Zoubeidi A, Gleave ME. Suppression of heat shock protein 27 using OGX-427 induces endoplasmic reticulum stress and potentiates heat shock protein 90 inhibitors to delay castrate-resistant prostate cancer. Eur Urol. 2014 Jul;66(1):145-55. doi: 10.1016/j.eururo.2013.12.019. Epub 2013 Dec 29. PubMed PMID: 24411988; PubMed Central PMCID: PMC4079118.

6: Zagouri F, Sergentanis TN, Chrysikos D, Papadimitriou CA, Dimopoulos MA, Psaltopoulou T. Hsp90 inhibitors in breast cancer: a systematic review. Breast. 2013 Oct;22(5):569-78. doi: 10.1016/j.breast.2013.06.003. Epub 2013 Jul 17. Review. PubMed PMID: 23870456.

7: Reddy N, Voorhees PM, Houk BE, Brega N, Hinson JM Jr, Jillela A. Phase I trial of the HSP90 inhibitor PF-04929113 (SNX5422) in adult patients with recurrent, refractory hematologic malignancies. Clin Lymphoma Myeloma Leuk. 2013 Aug;13(4):385-91. doi: 10.1016/j.clml.2013.03.010. Epub 2013 Jun 10. PubMed PMID: 23763921.

8: Jha KN, Coleman AR, Wong L, Salicioni AM, Howcroft E, Johnson GR. Heat shock protein 90 functions to stabilize and activate the testis-specific serine/threonine kinases, a family of kinases essential for male fertility. J Biol Chem. 2013 Jun 7;288(23):16308-20. doi: 10.1074/jbc.M112.400978. Epub 2013 Apr 18. PubMed PMID: 23599433; PubMed Central PMCID: PMC3675569.

9: Zagouri F, Bournakis E, Koutsoukos K, Papadimitriou CA. Heat shock protein 90 (hsp90) expression and breast cancer. Pharmaceuticals (Basel). 2012 Sep 12;5(9):1008-20. doi: 10.3390/ph5091008. PubMed PMID: 24280702; PubMed Central PMCID: PMC3816649.

10: Rajan A, Kelly RJ, Trepel JB, Kim YS, Alarcon SV, Kummar S, Gutierrez M, Crandon S, Zein WM, Jain L, Mannargudi B, Figg WD, Houk BE, Shnaidman M, Brega N, Giaccone G. A phase I study of PF-04929113 (SNX-5422), an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumor malignancies and lymphomas. Clin Cancer Res. 2011 Nov 1;17(21):6831-9. doi: 10.1158/1078-0432.CCR-11-0821. Epub 2011 Sep 9. PubMed PMID: 21908572; PubMed Central PMCID: PMC3207004.

11: Lamoureux F, Thomas C, Yin MJ, Kuruma H, Beraldi E, Fazli L, Zoubeidi A, Gleave ME. Clusterin inhibition using OGX-011 synergistically enhances Hsp90 inhibitor activity by suppressing the heat shock response in castrate-resistant prostate cancer. Cancer Res. 2011 Sep 1;71(17):5838-49. doi: 10.1158/0008-5472.CAN-11-0994. Epub 2011 Jul 7. PubMed PMID: 21737488.

12: Lamoureux F, Thomas C, Yin MJ, Kuruma H, Fazli L, Gleave ME, Zoubeidi A. A novel HSP90 inhibitor delays castrate-resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis. Clin Cancer Res. 2011 Apr 15;17(8):2301-13. doi: 10.1158/1078-0432.CCR-10-3077. Epub 2011 Feb 24. Erratum in: Clin Cancer Res. 2011 Jul 15;17(14):4916. PubMed PMID: 21349995; PubMed Central PMCID: PMC4437585.

13: Jain L, Gardner ER, Venitz J, Giaccone G, Houk BE, Figg WD. Determination of PF-04928473 in human plasma using liquid chromatography with tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Nov 15;878(30):3187-92. doi: 10.1016/j.jchromb.2010.09.017. Epub 2010 Sep 29. PubMed PMID: 20951100; PubMed Central PMCID: PMC2980813.

14: Fadden P, Huang KH, Veal JM, Steed PM, Barabasz AF, Foley B, Hu M, Partridge JM, Rice J, Scott A, Dubois LG, Freed TA, Silinski MA, Barta TE, Hughes PF, Ommen A, Ma W, Smith ED, Spangenberg AW, Eaves J, Hanson GJ, Hinkley L, Jenks M, Lewis M, Otto J, Pronk GJ, Verleysen K, Haystead TA, Hall SE. Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90. Chem Biol. 2010 Jul 30;17(7):686-94. doi: 10.1016/j.chembiol.2010.04.015. PubMed PMID: 20659681.

15: Huang KH, Veal JM, Fadden RP, Rice JW, Eaves J, Strachan JP, Barabasz AF, Foley BE, Barta TE, Ma W, Silinski MA, Hu M, Partridge JM, Scott A, DuBois LG, Freed T, Steed PM, Ommen AJ, Smith ED, Hughes PF, Woodward AR, Hanson GJ, McCall WS, Markworth CJ, Hinkley L, Jenks M, Geng L, Lewis M, Otto J, Pronk B, Verleysen K, Hall SE. Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents. J Med Chem. 2009 Jul 23;52(14):4288-305. doi: 10.1021/jm900230j. PubMed PMID: 19552433.

16: Rice JW, Veal JM, Barabasz A, Foley B, Fadden P, Scott A, Huang K, Steed P, Hall S. Targeting of multiple signaling pathways by the Hsp90 inhibitor SNX-2112 in EGFR resistance models as a single agent or in combination with erlotinib. Oncol Res. 2009;18(5-6):229-42. PubMed PMID: 20225761.

17: Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009 Jan 22;113(4):846-55. doi: 10.1182/blood-2008-04-151928. Epub 2008 Oct 23. PubMed PMID: 18948577; PubMed Central PMCID: PMC2630270.

18: Taldone T, Gozman A, Maharaj R, Chiosis G. Targeting Hsp90: small-molecule inhibitors and their clinical development. Curr Opin Pharmacol. 2008 Aug;8(4):370-4. doi: 10.1016/j.coph.2008.06.015. Epub 2008 Jul 31. Review. PubMed PMID: 18644253; PubMed Central PMCID: PMC2760289.