Tepotinib (discontinued)

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

MedKoo CAT#: 201145

CAS#: 1100598-32-0 (free base)

Description: Tepotinib was discontinued for commercial reason.


Chemical Structure

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Tepotinib (discontinued)
CAS# 1100598-32-0 (free base)

Theoretical Analysis

MedKoo Cat#: 201145
Name: Tepotinib (discontinued)
CAS#: 1100598-32-0 (free base)
Chemical Formula: C29H28N6O2
Exact Mass: 492.22737
Molecular Weight: 492.57
Elemental Analysis: C, 70.71; H, 5.73; N, 17.06; O, 6.50

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Pricing updated 2021-03-05. Prices are subject to change without notice.

Tepotinib was discontinued for commercial reason.

Related CAS #: 1100598-32-0 (free base)   Tepotinib HCl    

Synonym: EMD1214063 EMD1214063 EMD 1214063; MSC2156119; MSC-2156119; MS C2156119; Tepotinib.

IUPAC/Chemical Name: 3-(1-(3-(5-((1-methylpiperidin-4-yl)methoxy)pyrimidin-2-yl)benzyl)-1,6-dihydro-6-oxopyridazin-3-yl)benzonitrile

InChi Key: AHYMHWXQRWRBKT-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H28N6O2/c1-34-12-10-21(11-13-34)20-37-26-17-31-29(32-18-26)25-7-3-5-23(15-25)19-35-28(36)9-8-27(33-35)24-6-2-4-22(14-24)16-30/h2-9,14-15,17-18,21H,10-13,19-20H2,1H3

SMILES Code: N#CC1=CC=CC(C(C=C2)=NN(CC3=CC=CC(C4=NC=C(OCC5CCN(C)CC5)C=N4)=C3)C2=O)=C1

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

Handling Instructions:

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Soluble in DMSO, not in water 100.0

Preparing Stock Solutions

The following data is based on the product molecular weight 492.57 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.

Select a batch to recalculate based on the batch molecular weight:
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

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1: Takamori S, Matsubara T, Fujishita T, Ito K, Toyozawa R, Seto T, Yamaguchi M, Okamoto T. Dramatic intracranial response to tepotinib in a patient with lung adenocarcinoma harboring MET exon 14 skipping mutation. Thorac Cancer. 2021 Feb 3. doi: 10.1111/1759-7714.13871. Epub ahead of print. PMID: 33533182.

2: Pudelko L, Jaehrling F, Reusch C, Vitri S, Stroh C, Linde N, Sanderson MP, Musch D, Lebrun CJ, Keil M, Esdar C, Blaukat A, Rosell R, Schumacher KM, Karachaliou N. SHP2 Inhibition Influences Therapeutic Response to Tepotinib in Tumors with MET Alterations. iScience. 2020 Nov 20;23(12):101832. doi: 10.1016/j.isci.2020.101832. PMID: 33305187; PMCID: PMC7718487.

3: Tanaka H, Taima K, Makiguchi T, Nakagawa J, Niioka T, Tasaka S. Activity and bioavailability of tepotinib for leptomeningeal metastasis of NSCLC with MET exon 14 skipping mutation. Cancer Commun (Lond). 2021 Jan 2;41(1):83–7. doi: 10.1002/cac2.12124. Epub ahead of print. PMID: 33387444; PMCID: PMC7819565.

4: Aguado C, Giménez-Capitán A, Román R, Rodríguez S, Jordana-Ariza N, Aguilar A, Cabrera-Gálvez C, Rivas-Corredor C, Lianes P, Viteri S, Moya I, Molina-Vila MA. RNA-Based Multiplexing Assay for Routine Testing of Fusion and Splicing Variants in Cytological Samples of NSCLC Patients. Diagnostics (Basel). 2020 Dec 23;11(1):15. doi: 10.3390/diagnostics11010015. PMID: 33374879; PMCID: PMC7824402.

5: Roth KG, Mambetsariev I, Salgia R. Prolonged survival and response to tepotinib in a non-small-cell lung cancer patient with brain metastases harboring MET exon 14 mutation: a research report. Cold Spring Harb Mol Case Stud. 2020 Dec 17;6(6):a005785. doi: 10.1101/mcs.a005785. PMID: 33335011; PMCID: PMC7784494.

6: Abdelhameed AS, Attwa MW, Kadi AA. Identification of Iminium Intermediates Generation in the Metabolism of Tepotinib Using LC-MS/MS: In Silico and Practical Approaches to Bioactivation Pathway Elucidation. Molecules. 2020 Oct 28;25(21):5004. doi: 10.3390/molecules25215004. PMID: 33126762; PMCID: PMC7663698.

7: Sohn SH, Sul HJ, Kim B, Kim BJ, Kim HS, Zang DY. Tepotinib Inhibits the Epithelial-Mesenchymal Transition and Tumor Growth of Gastric Cancers by Increasing GSK3β, E-Cadherin, and Mucin 5AC and 6 Levels. Int J Mol Sci. 2020 Aug 21;21(17):6027. doi: 10.3390/ijms21176027. PMID: 32825724; PMCID: PMC7503648.

8: Blanc-Durand F, Alameddine R, Iafrate AJ, Tran-Thanh D, Lo YC, Blais N, Routy B, Tehfé M, Leduc C, Romeo P, Stephenson P, Florescu M. Tepotinib Efficacy in a Patient with Non-Small Cell Lung Cancer with Brain Metastasis Harboring an HLA- DRB1-MET Gene Fusion. Oncologist. 2020 Nov;25(11):916-920. doi: 10.1634/theoncologist.2020-0502. Epub 2020 Sep 8. PMID: 32716573; PMCID: PMC7648335.

9: Han S, Ma X, Fang J. [Progress on Mechanism of MET Gene Mutation and Targeted Drugs in Non-small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2020 Jul 20;23(7):609-614. Chinese. doi: 10.3779/j.issn.1009-3419.2020.102.32. PMID: 32702795; PMCID: PMC7406436.

10: Fujino T, Suda K, Mitsudomi T. Emerging MET tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. Expert Opin Emerg Drugs. 2020 Sep;25(3):229-249. doi: 10.1080/14728214.2020.1791821. Epub 2020 Jul 16. PMID: 32615820.

11: Romero D. Lung cancer at ASCO20 Virtual. Nat Rev Clin Oncol. 2020 Aug;17(8):450. doi: 10.1038/s41571-020-0405-z. PMID: 32533052.

12: Wu YL, Cheng Y, Zhou J, Lu S, Zhang Y, Zhao J, Kim DW, Soo RA, Kim SW, Pan H, Chen YM, Chian CF, Liu X, Tan DSW, Bruns R, Straub J, Johne A, Scheele J, Park K, Yang JC; INSIGHT Investigators. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. Lancet Respir Med. 2020 Nov;8(11):1132-1143. doi: 10.1016/S2213-2600(20)30154-5. Epub 2020 May 29. Erratum in: Lancet Respir Med. 2020 Jul;8(7):e59. PMID: 32479794.

13: Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, Mazieres J, Viteri S, Senellart H, Van Meerbeeck J, Raskin J, Reinmuth N, Conte P, Kowalski D, Cho BC, Patel JD, Horn L, Griesinger F, Han JY, Kim YC, Chang GC, Tsai CL, Yang JC, Chen YM, Smit EF, van der Wekken AJ, Kato T, Juraeva D, Stroh C, Bruns R, Straub J, Johne A, Scheele J, Heymach JV, Le X. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020 Sep 3;383(10):931-943. doi: 10.1056/NEJMoa2004407. Epub 2020 May 29. PMID: 32469185.

14: Markham A. Tepotinib: First Approval. Drugs. 2020 Jun;80(8):829-833. doi: 10.1007/s40265-020-01317-9. PMID: 32361823.

15: Shitara K, Yamazaki K, Tsushima T, Naito T, Matsubara N, Watanabe M, Sarholz B, Johne A, Doi T. Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors. Jpn J Clin Oncol. 2020 Aug 4;50(8):859-866. doi: 10.1093/jjco/hyaa042. PMID: 32328660; PMCID: PMC7401714.

16: Huang C, Zou Q, Liu H, Qiu B, Li Q, Lin Y, Liang Y. Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations. Curr Treat Options Oncol. 2020 Apr 18;21(4):33. doi: 10.1007/s11864-020-0723-5. PMID: 32306194.

17: Russo A, Lopes AR, McCusker MG, Garrigues SG, Ricciardi GR, Arensmeyer KE, Scilla KA, Mehra R, Rolfo C. New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1). Curr Oncol Rep. 2020 Apr 16;22(5):48. doi: 10.1007/s11912-020-00909-8. PMID: 32296961.

18: Johne A, Scheible H, Becker A, van Lier JJ, Wolna P, Meyring M. Open-label, single-center, phase I trial to investigate the mass balance and absolute bioavailability of the highly selective oral MET inhibitor tepotinib in healthy volunteers. Invest New Drugs. 2020 Oct;38(5):1507-1519. doi: 10.1007/s10637-020-00926-1. Epub 2020 Mar 27. PMID: 32221754; PMCID: PMC7497692.

19: Falchook GS, Kurzrock R, Amin HM, Xiong W, Fu S, Piha-Paul SA, Janku F, Eskandari G, Catenacci DV, Klevesath M, Bruns R, Stammberger U, Johne A, Bladt F, Friese-Hamim M, Girard P, El Bawab S, Hong DS. First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors. Clin Cancer Res. 2020 Mar 15;26(6):1237-1246. doi: 10.1158/1078-0432.CCR-19-2860. Epub 2019 Dec 10. PMID: 31822497.

20: Heydt C, Becher AK, Wagener-Ryczek S, Ball M, Schultheis AM, Schallenberg S, Rüsseler V, Büttner R, Merkelbach-Bruse S. Comparison of in situ and extraction-based methods for the detection of MET amplifications in solid tumors. Comput Struct Biotechnol J. 2019 Sep 11;17:1339-1347. doi: 10.1016/j.csbj.2019.09.003. PMID: 31762957; PMCID: PMC6861603.



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