WARNING: This product is for research use only, not for human or veterinary use.
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.
MedKoo Cat#: 206835
Name: PF-04929113 mesylate
CAS#: 1173111-67-5 (mesylate)
Chemical Formula: C26H34F3N5O7S
Molecular Weight: 617.64
Elemental Analysis: C, 50.56; H, 5.55; F, 9.23; N, 11.34; O, 18.13; S, 5.19
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
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).
HS Tariff Code: 2934.99.9001
|Biological target:||PF 04217903 mesylate is a highly selective, high affinity MET inhibitor (Ki = 6-7 nM against wild type c-Met).|
|In vitro activity:||PF-04928473 inhibited cell growth in a panel of prostate cancer cells, induced cell cycle arrest at sub-G1 and led to apoptosis and increased caspase-3 activity. These biologic events were accompanied by decreased activation of Akt and Erk as well as decreased expression of Her2, and decreased AR expression and activation in vitro. PF-04928473 abrogated RANKL-induced osteoclast differentiation by affecting NF-kB activation and Src phosphorylation. Reference: Clin Cancer Res. 2011 Jul 15;17(14):4916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437585/|
|In vivo activity:||The effects of PF-04929113 on castrate-resistant LNCaP tumor growth were evaluated. Mice treated with PF-04929113 (n=8) exhibited a significant decrease in tumor volume compared with control mice starting at the day 17 (240mm3 and 1293.9mm3, respectively) and after 45 days (459.2mm3 and 2818.2mm3, respectively; Fig. 3A). When each animal was considered individually, the incidence of mice progressing with a tumor volume ≥ 500mm3 was significantly diminished by day 22 in PF-04929113-treated animals (0/8) compared with controls (8/8, Fig 3B). Rate of tumor progression at days 10 and 45 was also significantly decreased (1947.8mm3 for control mice vs 244.1mm3 for treated mice, p<0.001) in the treatment group, compared with control mice (Fig 3C). Consequently, progression-free (p<0.001) and cancer specific (p<0.001) survival were significantly prolonged in the PF-04929113-treated group (Fig 3D). These data demonstrate that targeting Hsp90 by PF-04929113 significantly inhibits castrate resistant tumor growth and prolongs survival in the LNCaP tumor model. Reference: Clin Cancer Res. 2011 Jul 15;17(14):4916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437585/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 617.64 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:||1. 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. PMID: 21349995; PMCID: PMC4437585.|
|In vitro protocol:||1. 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. PMID: 21349995; PMCID: PMC4437585.|
|In vivo protocol:||1. 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. PMID: 21349995; PMCID: PMC4437585.|
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.