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MedKoo Cat#: 206217 | Name: PF-04929113 free base
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

PF-04929113 free base
PF-04929113 free base
CAS#908115-27-5 (free base)

Theoretical Analysis

MedKoo Cat#: 206217

Name: PF-04929113 free base

CAS#: 908115-27-5 (free base)

Chemical Formula: C25H30F3N5O4

Exact Mass: 521.2250

Molecular Weight: 521.53

Elemental Analysis: C, 57.57; H, 5.80; F, 10.93; N, 13.43; O, 12.27

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,650.00 Ready to ship
1g USD 3,850.00 Ready to ship
2g USD 6,450.00 2 Weeks
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Related CAS #
908115-27-5 (free base) 1173111-67-5 (mesylate)
Synonym
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
InChi Key
AVDSOVJPJZVBTC-CTYIDZIISA-N
InChi Code
InChI=1S/C25H30F3N5O4/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/h5,8-9,13,15,31H,3-4,6-7,10-12,29H2,1-2H3,(H2,30,36)/t13-,15-
SMILES Code
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, 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
  Hsp90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation or immune responses.       
Biological target:
PF-04929113 (SNX-5422) is a potent and selective HSP90 inhibitor with Kd of 41 nM and induces Her-2 degradation with IC50 of 37 nM.
In vitro activity:
All compounds summarized showed potent antiproliferative activity against a broad range of cancer cell types (Table 5). Compound (10) exhibited potent effects on Her2 stability and caused expected up-regulation of Hsp70 (Table 6). Additionally, treatment with the inhibitor down regulated both the MAPK and AKT signaling pathways as measured by the loss of p-S6 and p-ERK in treated cells. These pathways are implicated in uncontrolled cellular division and antiapoptotic signaling and have been targeted for drug development. Reference: J Med Chem. 2009 Jul 23;52(14):4288-305. https://doi.org/10.1021/jm900230j
In vivo activity:
Shown in Figure 8 is the in vivo antitumor activity of PF-04929113 (10) in an HT-29 human colon tumor xenograft model. The compound was orally administered to mice bearing subcutaneous tumors 3 times a week for 3 weeks (qod × 3/2 × 3) at 5, 10, 25, and 50 mg/kg. The 50 mg/kg dose was the most efficacious, demonstrating a 67% growth delay over vehicle control. Median time to end point (TTE) for the 50 mg/kg group was 43.2 days compared to 25.9 days for vehicle control. Two of 10 animals survived to the end of the study (61 days). The 25 mg/kg dose showed tumor growth delay but at a much lower percentage (14%). Median TTE was not statistically significant over vehicle control. On the basis of body weight measurements and clinical observations, compound 10 was well tolerated at all dose levels tested. No treatment related deaths were observed. Reference: J Med Chem. 2009 Jul 23;52(14):4288-305. https://doi.org/10.1021/jm900230j
Solvent mg/mL mM
Solubility
DMSO 1.0 1.90
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 521.53 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.

Recalculate based on batch purity %
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. 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. PMID: 19552433.
In vivo protocol:
1. 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. PMID: 19552433. 2. 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: Srivastava RK, Muzaffar S, Khan J, Crossman DK, Agarwal A, Athar M. HSP90, a Common Therapeutic Target for Suppressing Skin Injury Caused by Exposure to Chemically Diverse Classes of Blistering Agents. J Pharmacol Exp Ther. 2024 Jan 17;388(2):546-559. doi: 10.1124/jpet.123.001795. PMID: 37914412; PMCID: PMC10801768. 2: Oikonomou A, Valsecchi L, Quadri M, Watrin T, Scharov K, Procopio S, Tu JW, Vogt M, Savino AM, Silvestri D, Valsecchi MG, Biondi A, Borkhardt A, Bhatia S, Cazzaniga G, Fazio G, Bardini M, Palmi C. High-throughput screening as a drug repurposing strategy for poor outcome subgroups of pediatric B-cell precursor Acute Lymphoblastic Leukemia. Biochem Pharmacol. 2023 Nov;217:115809. doi: 10.1016/j.bcp.2023.115809. Epub 2023 Sep 17. PMID: 37717691. 3: Goswami R, Russell VS, Tu JJ, Thomas C, Hughes P, Kelly F, Langel SN, Steppe J, Palmer SM, Haystead T, Blasi M, Permar SR. Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells. iScience. 2021 Dec 17;24(12):103412. doi: 10.1016/j.isci.2021.103412. Epub 2021 Nov 10. PMID: 34786537; PMCID: PMC8579697. 4: Gutierrez M, Guo R, Giaccone G, Liu SV, Hao Z, Hilton C, Hinson JM Jr, Kris MG, Orlemans EO, Drilon A. Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers. Lung Cancer. 2021 Dec;162:23-28. doi: 10.1016/j.lungcan.2021.10.001. Epub 2021 Oct 8. PMID: 34655925; PMCID: PMC8642306. 5: Yao X, Jing T, Wang T, Gu C, Chen X, Chen F, Feng H, Zhao H, Chen D, Ma W. Molecular Characterization and Elucidation of Pathways to Identify Novel Therapeutic Targets in Pulmonary Arterial Hypertension. Front Physiol. 2021 Jul 23;12:694702. doi: 10.3389/fphys.2021.694702. PMID: 34366885; PMCID: PMC8346036. 6: Albakova Z, Mangasarova Y, Sapozhnikov A. Heat Shock Proteins in Lymphoma Immunotherapy. Front Immunol. 2021 Mar 18;12:660085. doi: 10.3389/fimmu.2021.660085. PMID: 33815422; PMCID: PMC8012763. 7: Chen TL, Harrington B, Truxall J, Wasmuth R, Prouty A, Sloan S, Lehman AM, Sampath D, Orlemans E, Baiocchi RA, Alinari L, Byrd JC, Woyach JA, Hertlein E. Preclinical evaluation of the Hsp90 inhibitor SNX-5422 in ibrutinib resistant CLL. J Hematol Oncol. 2021 Feb 24;14(1):36. doi: 10.1186/s13045-021-01039-9. PMID: 33627156; PMCID: PMC7905592. 8: Kim SH, Cho YK, Huh JH, Kang JG, Ihm SH, Choi MG, Lee SJ. Heat Shock Protein 90 Inhibitors AUY922, BIIB021 and SNX5422 Induce Bim-mediated Death of Thyroid Carcinoma Cells. Anticancer Res. 2020 Nov;40(11):6137-6150. doi: 10.21873/anticanres.14634. PMID: 33109551. 9: Nazar A, Abbas G, Azam SS. Deciphering the Inhibition Mechanism of under Trial Hsp90 Inhibitors and Their Analogues: A Comparative Molecular Dynamics Simulation. J Chem Inf Model. 2020 Aug 24;60(8):3812-3830. doi: 10.1021/acs.jcim.9b01134. Epub 2020 Aug 3. PMID: 32659088. 10: Chen L, Wang M, Lin Z, Yao M, Wang W, Cheng S, Li B, Zhang Y, Yin Q. Mild microwave ablation combined with HSP90 and TGF‑β1 inhibitors enhances the therapeutic effect on osteosarcoma. Mol Med Rep. 2020 Aug;22(2):906-914. doi: 10.3892/mmr.2020.11173. Epub 2020 May 22. PMID: 32468060; PMCID: PMC7339669. 11: Sima N, Sun W, Gorshkov K, Shen M, Huang W, Zhu W, Xie X, Zheng W, Cheng X. Small Molecules Identified from a Quantitative Drug Combinational Screen Resensitize Cisplatin's Response in Drug-Resistant Ovarian Cancer Cells. Transl Oncol. 2018 Aug;11(4):1053-1064. doi: 10.1016/j.tranon.2018.06.002. Epub 2018 Jul 5. PMID: 29982103; PMCID: PMC6034569. 12: 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. PMID: 26219406. 13: 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. doi: 10.2174/1568026615666150112113627. PMID: 25579569. 14: 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. PMID: 25262379. 15: 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. PMID: 24820073; PMCID: PMC4068574. 16: 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. Erratum in: Eur Urol. 2016 Jul;70(1):e27-e28. doi: 10.1016/j.eururo.2016.03.014. PMID: 24411988; PMCID: PMC4079118. 17: 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. PMID: 23870456. 18: 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. PMID: 23763921. 19: 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):16308-16320. doi: 10.1074/jbc.M112.400978. Epub 2013 Apr 18. PMID: 23599433; PMCID: PMC3675569. 20: 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. PMID: 24280702; PMCID: PMC3816649.