PF-04217903 | CAS#956905-27-4 | 956906-93-7 | 1159490-81-9 | 1159490-83-1 | MET inhibitor

MedKoo Cat#: 202221 | Name: PF-04217903

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 a n 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

CAS#956905-27-4 (free base)

Theoretical Analysis

MedKoo Cat#: 202221

Name: PF-04217903

CAS#: 956905-27-4 (free base)

Chemical Formula: C19H16N8O

Exact Mass: 372.1447

Molecular Weight: 372.38

Elemental Analysis: C, 61.28; H, 4.33; N, 30.09; O, 4.30

Price and Availability

Size	Price	Availability
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 1,350.00	Ready to ship
500mg	USD 2,850.00	Ready to ship

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Related CAS #

956905-27-4 (free base) 956906-93-7 (mesylate) 1159490-85-3 (phenolsulfonate) 1159490-83-1 (monophosphate)

Synonym

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

InChi Key

PDMUGYOXRHVNMO-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H16N8O/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/h1-5,8-10,12,28H,6-7,11H2

SMILES Code

OCCN1N=CC(C2=CN=C3C(N(CC4=CC=C5N=CC=CC5=C4)N=N3)=N2)=C1

Appearance

white 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC40808

QC Data

View QC data: current batch, Lot#BBC40808

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PF-04217903 is a c-Met kinase inhibitor with a Ki of 4.8 nM for human c-Met.

In vitro activity:

The antiangiogenic activity of PF-04217903 was evaluated in vitro. PF-04217903 inhibited HGF-stimulated c-Met phosphorylation in HUVECs with an IC50 value of 4.6 nmol/L (Supplementary Table S1). In endothelial cell functional assays, PF-04217903 inhibited HGF-mediated HUVEC survival (IC50 = 12 nmol/L), Matrigel invasion (IC50 = 27 nmol/L), and induced HUVEC apoptosis (IC50 = 7 nmol/L; Table 1). Reference: Mol Cancer Ther. 2012 Apr;11(4):1036-47. https://mct.aacrjournals.org/content/11/4/1036.long

In vivo activity:

PF-04217903 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. Antitumor efficacy of PF-04217903 was dose-dependent and showed a strong correlation with inhibition of c-Met phosphorylation, downstream signaling, and tumor cell proliferation/survival. Furthermore, PF-04217903 strongly induced phospho-PDGFRβ (platelet-derived growth factor receptor) levels in U87MG xenograft tumors, indicating a possible oncogene switching mechanism in tumor cell signaling as a potential resistance mechanism that might compromise tumor responses to c-Met inhibitors. Reference: Mol Cancer Ther. 2012 Apr;11(4):1036-47. https://mct.aacrjournals.org/content/11/4/1036.long

	Solvent	mg/mL	mM
Solubility
	DMSO	5.0	13.40

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 372.38 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. 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.

In vitro protocol:

In vivo protocol:

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.