MedKoo Cat#: 206862 | Name: PF-04217903 mesylate
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Description:

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

PF-04217903 is a MET tyrosine kinase inhibitor, is also an orally bioavailabe, small-molecule tyrosine kinase inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor PF-04217903 selectively binds to and inhibits c-Met, disrupting the c-Met signaling pathway, which may result in the inhibition of tumor cell growth, migration and invasion of tumor cells, and the induction of death in tumor cells expressing c-Met.

Chemical Structure

PF-04217903 mesylate
PF-04217903 mesylate
CAS#956906-93-7 (mesylate)

Theoretical Analysis

MedKoo Cat#: 206862

Name: PF-04217903 mesylate

CAS#: 956906-93-7 (mesylate)

Chemical Formula: C20H20N8O4S

Exact Mass: 0.0000

Molecular Weight: 468.49

Elemental Analysis: C, 51.28; H, 4.30; N, 23.92; O, 13.66; S, 6.84

Price and Availability

Size Price Availability Quantity
50mg USD 350.00 2 weeks
100mg USD 600.00 2 weeks
250mg USD 1,250.00 2 weeks
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Synonym
PF-04217903 mesylate; PF04217903; PF 04217903; PF-04217903; PF4217903; PF-4217903; PF 4217903.
IUPAC/Chemical Name
2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol mesylate
InChi Key
HBEMHKVWZJTVOC-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H16N8O.CH4O3S/c28-7-6-26-12-15(9-22-26)17-10-21-18-19(23-17)27(25-24-18)11-13-3-4-16-14(8-13)2-1-5-20-16;1-5(2,3)4/h1-5,8-10,12,28H,6-7,11H2;1H3,(H,2,3,4)
SMILES Code
OCCN1N=CC(C2=CN=C3C(N(CC4=CC=C5N=CC=CC5=C4)N=N3)=N2)=C1.OS(=O)(C)=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
More Info
Product Data
Biological target:
PF-04217903 mesylate is a potent ATP-competitive c-Met kinase inhibitor with Ki of 4.8 nM for human c-Met.
In vitro activity:
PF-04217903 showed more than 1,000-fold selectivity for c-Met compared with more than 150 kinases, making it one of the most selective c-Met inhibitors described to date. PF-04217903 inhibited tumor cell proliferation, survival, migration/invasion in MET-amplified cell lines in vitro, and showed marked antitumor activity in tumor models harboring either MET gene amplification or a hepatocyte growth factor (HGF)/c-Met autocrine loop at well-tolerated dose levels in vivo. Reference: Mol Cancer Ther. 2012 Apr;11(4):1036-47. https://pubmed.ncbi.nlm.nih.gov/22389468/
In vivo activity:
Medicinal chemistry lead optimization produced 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (2, PF-04217903), an extremely potent and exquisitely selective c-MET inhibitor. 2 demonstrated effective tumor growth inhibition in c-MET dependent tumor models with good oral PK properties and an acceptable safety profile in preclinical studies. 2 progressed to clinical evaluation in a Phase I oncology setting. Reference: J Med Chem. 2012 Sep 27;55(18):8091-109. https://pubmed.ncbi.nlm.nih.gov/22924734/
Solvent mg/mL mM
Solubility
DMSO 48.4 103.36
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 468.49 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:
1. Zou HY, Li Q, Lee JH, Arango ME, Burgess K, Qiu M, Engstrom LD, Yamazaki S, Parker M, Timofeevski S, Cui JJ, McTigue M, Los G, Bender SL, Smeal T, Christensen JG. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012 Apr;11(4):1036-47. doi: 10.1158/1535-7163.MCT-11-0839. Epub 2012 Mar 2. PMID: 22389468. 2. Dillon R, Nilsson CL, Shi SD, Lee NV, Krastins B, Greig MJ. Discovery of a novel B-Raf fusion protein related to c-Met drug resistance. J Proteome Res. 2011 Nov 4;10(11):5084-94. doi: 10.1021/pr200498v. Epub 2011 Oct 12. PMID: 21936566. 3. Felix FB, Dias J, Vago JP, Martins DG, Beltrami VA, Fernandes DO, Menezes Dos Santos ACP, Queiroz-Junior CM, de Sousa LP, Amaral FA, Soriani FM, Teixeira MM, Pinho V. Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis. Pharmacol Res. 2023 Feb;188:106640. doi: 10.1016/j.phrs.2022.106640. Epub 2023 Jan 7. PMID: 36627004. 4. Cui JJ, McTigue M, Nambu M, Tran-Dubé M, Pairish M, Shen H, Jia L, Cheng H, Hoffman J, Le P, Jalaie M, Goetz GH, Ryan K, Grodsky N, Deng YL, Parker M, Timofeevski S, Murray BW, Yamazaki S, Aguirre S, Li Q, Zou H, Christensen J. Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer. J Med Chem. 2012 Sep 27;55(18):8091-109. doi: 10.1021/jm300967g. Epub 2012 Sep 10. Erratum in: J Med Chem. 2012 Nov 26;55(22):10314. PMID: 22924734.
In vitro protocol:
1. Zou HY, Li Q, Lee JH, Arango ME, Burgess K, Qiu M, Engstrom LD, Yamazaki S, Parker M, Timofeevski S, Cui JJ, McTigue M, Los G, Bender SL, Smeal T, Christensen JG. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012 Apr;11(4):1036-47. doi: 10.1158/1535-7163.MCT-11-0839. Epub 2012 Mar 2. PMID: 22389468. 2. Dillon R, Nilsson CL, Shi SD, Lee NV, Krastins B, Greig MJ. Discovery of a novel B-Raf fusion protein related to c-Met drug resistance. J Proteome Res. 2011 Nov 4;10(11):5084-94. doi: 10.1021/pr200498v. Epub 2011 Oct 12. PMID: 21936566.
In vivo protocol:
1. Felix FB, Dias J, Vago JP, Martins DG, Beltrami VA, Fernandes DO, Menezes Dos Santos ACP, Queiroz-Junior CM, de Sousa LP, Amaral FA, Soriani FM, Teixeira MM, Pinho V. Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis. Pharmacol Res. 2023 Feb;188:106640. doi: 10.1016/j.phrs.2022.106640. Epub 2023 Jan 7. PMID: 36627004. 2. Cui JJ, McTigue M, Nambu M, Tran-Dubé M, Pairish M, Shen H, Jia L, Cheng H, Hoffman J, Le P, Jalaie M, Goetz GH, Ryan K, Grodsky N, Deng YL, Parker M, Timofeevski S, Murray BW, Yamazaki S, Aguirre S, Li Q, Zou H, Christensen J. Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer. J Med Chem. 2012 Sep 27;55(18):8091-109. doi: 10.1021/jm300967g. Epub 2012 Sep 10. Erratum in: J Med Chem. 2012 Nov 26;55(22):10314. PMID: 22924734.
1: Zhou W, Lin L, Chen D, Wang J, Chen J. Construction of a Liver Cancer Prognostic Model Based on Interferon-Gamma-Related Genes for Revealing the Immune Landscape. J Environ Pathol Toxicol Oncol. 2024;43(4):25-42. doi: 10.1615/JEnvironPatholToxicolOncol.2024049848. PMID: 39016139. 2: Zhang R, Hao C, Ji Z, Qu Y, Zuo W, Yang M, Zuo P, Carvalho A, Ma G, Li Y. Upregulation of Biomarker Limd1 Was Correlated with Immune Infiltration in Doxorubicin-Related Cardiotoxicity. Mediators Inflamm. 2023 Mar 23;2023:8347759. doi: 10.1155/2023/8347759. PMID: 37009626; PMCID: PMC10063360. 3: Felix FB, Dias J, Vago JP, Martins DG, Beltrami VA, Fernandes DO, Menezes Dos Santos ACP, Queiroz-Junior CM, de Sousa LP, Amaral FA, Soriani FM, Teixeira MM, Pinho V. Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis. Pharmacol Res. 2023 Feb;188:106640. doi: 10.1016/j.phrs.2022.106640. Epub 2023 Jan 7. PMID: 36627004. 4: Cheng HS, Marvalim C, Zhu P, Law CLD, Low ZYJ, Chong YK, Ang BT, Tang C, Tan NS. Kinomic profile in patient-derived glioma cells during hypoxia reveals c-MET-PI3K dependency for adaptation. Theranostics. 2021 Mar 5;11(11):5127-5142. doi: 10.7150/thno.54741. PMID: 33859738; PMCID: PMC8039937. 5: Jenke R, Holzhäuser-Rein M, Mueller-Wilke S, Lordick F, Aigner A, Büch T. SATB1-Mediated Upregulation of the Oncogenic Receptor Tyrosine Kinase HER3 Antagonizes MET Inhibition in Gastric Cancer Cells. Int J Mol Sci. 2020 Dec 23;22(1):82. doi: 10.3390/ijms22010082. PMID: 33374770; PMCID: PMC7796274. 6: Wu Y, Fan Q, Zeng F, Zhu J, Chen J, Fan D, Li X, Duan W, Guo Q, Cao Z, Briley-Saebo K, Li C, Tao X. Peptide-Functionalized Nanoinhibitor Restrains Brain Tumor Growth by Abrogating Mesenchymal-Epithelial Transition Factor (MET) Signaling. Nano Lett. 2018 Sep 12;18(9):5488-5498. doi: 10.1021/acs.nanolett.8b01879. Epub 2018 Aug 3. PMID: 30067910. 7: Knauf JA, Luckett KA, Chen KY, Voza F, Socci ND, Ghossein R, Fagin JA. Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers. J Clin Invest. 2018 Aug 31;128(9):4086-4097. doi: 10.1172/JCI120966. Epub 2018 Aug 20. PMID: 29990309; PMCID: PMC6118575. 8: Yan L, Zhang L, Zhang Y, Qiao X, Pan J, Liu H, Lu S, Xiang B, Lu T, Yuan H. Insight into the key features for ligand binding in Y1230 mutated c-Met kinase domain by molecular dynamics simulations. J Biomol Struct Dyn. 2018 Jun;36(8):2015-2031. doi: 10.1080/07391102.2017.1340852. Epub 2017 Jun 20. PMID: 28599617. 9: Yu LL, Liu YJ, Wang ZH, Shi L, Liu LX. The study of endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms. Eur Rev Med Pharmacol Sci. 2017 Feb;21(4):795-803. Retraction in: Eur Rev Med Pharmacol Sci. 2017 Mar;21(6):1176. PMID: 28272703. 10: Yeh I, Botton T, Talevich E, Shain AH, Sparatta AJ, de la Fouchardiere A, Mully TW, North JP, Garrido MC, Gagnon A, Vemula SS, McCalmont TH, LeBoit PE, Bastian BC. Activating MET kinase rearrangements in melanoma and Spitz tumours. Nat Commun. 2015 May 27;6:7174. doi: 10.1038/ncomms8174. PMID: 26013381; PMCID: PMC4446791. 11: Peña-Silva RA, Chalouhi N, Wegman-Points L, Ali M, Mitchell I, Pierce GL, Chu Y, Ballas ZK, Heistad D, Hasan D. Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms. Hypertension. 2015 Mar;65(3):587-93. doi: 10.1161/HYPERTENSIONAHA.114.04681. Epub 2014 Dec 15. PMID: 25510828; PMCID: PMC4326566. 12: Matte I, Lane D, Laplante C, Garde-Granger P, Rancourt C, Piché A. Ovarian cancer ascites enhance the migration of patient-derived peritoneal mesothelial cells via cMet pathway through HGF-dependent and -independent mechanisms. Int J Cancer. 2015 Jul 15;137(2):289-98. doi: 10.1002/ijc.29385. Epub 2014 Dec 18. PMID: 25482018. 13: Zhang Y, Xue D, Wang X, Lu M, Gao B, Qiao X. Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways. Mol Med Rep. 2014 Jan;9(1):83-90. doi: 10.3892/mmr.2013.1781. Epub 2013 Nov 7. PMID: 24213221. 14: Diamond JR, Salgia R, Varella-Garcia M, Kanteti R, LoRusso PM, Clark JW, Xu LG, Wilner K, Eckhardt SG, Ching KA, Lira ME, Schoenmakers EF, Christensen JG, Camidge DR. Initial clinical sensitivity and acquired resistance to MET inhibition in MET-mutated papillary renal cell carcinoma. J Clin Oncol. 2013 Jun 1;31(16):e254-8. doi: 10.1200/JCO.2012.46.4289. Epub 2013 Apr 22. PMID: 23610116; PMCID: PMC3661938. 15: Sennino B, Ishiguro-Oonuma T, Schriver BJ, Christensen JG, McDonald DM. Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice. Cancer Res. 2013 Jun 15;73(12):3692-703. doi: 10.1158/0008-5472.CAN-12-2160. Epub 2013 Apr 10. PMID: 23576559; PMCID: PMC3686901. 16: Cui JJ, McTigue M, Nambu M, Tran-Dubé M, Pairish M, Shen H, Jia L, Cheng H, Hoffman J, Le P, Jalaie M, Goetz GH, Ryan K, Grodsky N, Deng YL, Parker M, Timofeevski S, Murray BW, Yamazaki S, Aguirre S, Li Q, Zou H, Christensen J. Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazi n-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer. J Med Chem. 2012 Sep 27;55(18):8091-109. doi: 10.1021/jm300967g. Epub 2012 Sep 10. Erratum in: J Med Chem. 2012 Nov 26;55(22):10314. PMID: 22924734. 17: Lee NV, Lira ME, Pavlicek A, Ye J, Buckman D, Bagrodia S, Srinivasa SP, Zhao Y, Aparicio S, Rejto PA, Christensen JG, Ching KA. A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through [corrected] MAPK activation. PLoS One. 2012;7(6):e39653. doi: 10.1371/journal.pone.0039653. Epub 2012 Jun 22. Erratum in: PLoS One. 2012;7(8). doi: 10.1371/annotation/d988dd75-bcd2-4859-b20b-487e1bf2513b. PMID: 22745804; PMCID: PMC3382171. 18: Sennino B, Ishiguro-Oonuma T, Wei Y, Naylor RM, Williamson CW, Bhagwandin V, Tabruyn SP, You WK, Chapman HA, Christensen JG, Aftab DT, McDonald DM. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer Discov. 2012 Mar;2(3):270-87. doi: 10.1158/2159-8290.CD-11-0240. Epub 2012 Feb 24. PMID: 22585997; PMCID: PMC3354652. 19: Zou HY, Li Q, Lee JH, Arango ME, Burgess K, Qiu M, Engstrom LD, Yamazaki S, Parker M, Timofeevski S, Cui JJ, McTigue M, Los G, Bender SL, Smeal T, Christensen JG. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012 Apr;11(4):1036-47. doi: 10.1158/1535-7163.MCT-11-0839. Epub 2012 Mar 2. PMID: 22389468. 20: Dillon R, Nilsson CL, Shi SD, Lee NV, Krastins B, Greig MJ. Discovery of a novel B-Raf fusion protein related to c-Met drug resistance. J Proteome Res. 2011 Nov 4;10(11):5084-94. doi: 10.1021/pr200498v. Epub 2011 Oct 12. PMID: 21936566.