Capmatinib HCl hydrate

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

MedKoo CAT#: 109735

CAS#: 1865733-40-9 (HCl hydrate)

Description: Capmatinib, also known as INCB28060 and INC280, is an orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor INC280 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. Capmatinib was approved in 2020.

Chemical Structure

Capmatinib HCl hydrate
CAS# 1865733-40-9 (HCl hydrate)

Theoretical Analysis

MedKoo Cat#: 109735
Name: Capmatinib HCl hydrate
CAS#: 1865733-40-9 (HCl hydrate)
Chemical Formula: C23H21Cl2FN6O2
Exact Mass: 0.00
Molecular Weight: 503.359
Elemental Analysis: C, 54.88; H, 4.21; Cl, 14.09; F, 3.77; N, 16.70; O, 6.36

Price and Availability

Size Price Availability Quantity
200mg USD 1250 3~4 weeks
500mg USD 1950 3~4 weeks
1g USD 2950 3~4 weeks
2g USD 5250 3~4 weeks
5g USD 8650 3~4 weeks
Bulk inquiry

Related CAS #: 1029712-80-8 (free base)   1865733-40-9 (HCl hydrate)   1029714-89-3 (xHCl)   1197376-85-4 (2HCl)   1197376-90-1 (besylate)   1450883-33-6 (fumarate)    

Synonym: Capmatinib hydrochloride; NVP-INC 280AAA; INC280; INC-280; INC 280; INCB028060; INCB-028060; INCB 028060; INCB28060; INCB-28060; INCB 28060; Capmatinib.

IUPAC/Chemical Name: 2-Fluoro-N-methyl-4-[7-[(quinolin-6-yl)methyl]imidazo[1,2-b]-[1,2,4]triazin-2-yl]benzamide dihydrochloride hydrate


InChi Code: InChI=1S/C23H17FN6O.2ClH.H2O/c1-25-22(31)18-6-5-16(11-19(18)24)21-13-28-23-27-12-17(30(23)29-21)10-14-4-7-20-15(9-14)3-2-8-26-20;;;/h2-9,11-13H,10H2,1H3,(H,25,31);2*1H;1H2

SMILES Code: O=C(NC)C1=CC=C(C2=NN3C(N=C2)=NC=C3CC4=CC=C5N=CC=CC5=C4)C=C1F.[H]Cl.[H]Cl.[H]O[H]

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: >3 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: 1: Vansteenkiste JF, Van De Kerkhove C, Wauters E, Van Mol P. Capmatinib for the treatment of non-small cell lung cancer. Expert Rev Anticancer Ther. 2019 Aug;19(8):659-671. doi: 10.1080/14737140.2019.1643239. Epub 2019 Aug 1. PMID: 31368815. 2: Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW. Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR- Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Nov 1;36(31):3101-3109. doi: 10.1200/JCO.2018.77.7326. Epub 2018 Aug 29. Erratum in: J Clin Oncol. 2019 Jan 20;37(3):261. PMID: 30156984. 3: Baltschukat S, Engstler BS, Huang A, Hao HX, Tam A, Wang HQ, Liang J, DiMare MT, Bhang HC, Wang Y, Furet P, Sellers WR, Hofmann F, Schoepfer J, Tiedt R. Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation. Clin Cancer Res. 2019 May 15;25(10):3164-3175. doi: 10.1158/1078-0432.CCR-18-2814. Epub 2019 Jan 23. PMID: 30674502. 4: Capmatinib Triggers Responses in NSCLC. Cancer Discov. 2019 Jan;9(1):OF6. doi: 10.1158/2159-8290.CD-NB2018-148. Epub 2018 Nov 14. PMID: 30429129. 5: Esaki T, Hirai F, Makiyama A, Seto T, Bando H, Naito Y, Yoh K, Ishihara K, Kakizume T, Natsume K, Myers A, Doi T. Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors. Cancer Sci. 2019 Apr;110(4):1340-1351. doi: 10.1111/cas.13956. Epub 2019 Feb 20. PMID: 30724423; PMCID: PMC6447844. 6: Ko B, Halmos B. Capmatinib and gefitinib combination therapy: will EGFR- mutated MET-dysregulated NSCLC "capitulate"? Transl Lung Cancer Res. 2018 Dec;7(Suppl 4):S321-S325. doi: 10.21037/tlcr.2018.12.05. PMID: 30705845; PMCID: PMC6328688. 7: Kim S, Kim TM, Kim DW, Kim S, Kim M, Ahn YO, Keam B, Heo DS. Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib. Cancer Res Treat. 2019 Jul;51(3):951-962. doi: 10.4143/crt.2018.052. Epub 2018 Oct 10. PMID: 30309221; PMCID: PMC6639226. 8: Dhillon S. Capmatinib: First Approval. Drugs. 2020 Jul;80(11):1125-1131. doi: 10.1007/s40265-020-01347-3. PMID: 32557339. 9: Capmatinib Could Alter NSCLC Treatment Landscape. Cancer Discov. 2020 Jun;10(6):OF4. doi: 10.1158/2159-8290.CD-NB2020-038. Epub 2020 Apr 29. PMID: 32349974. 10: Burki TK. Preliminary activity of capmatinib with gefitinib in NSCLC. Lancet Oncol. 2018 Oct;19(10):e517. doi: 10.1016/S1470-2045(18)30678-8. Epub 2018 Sep 6. PMID: 30197173. 11: Bang YJ, Su WC, Schuler M, Nam DH, Lim WT, Bauer TM, Azaro A, Poon RTP, Hong D, Lin CC, Akimov M, Ghebremariam S, Zhao S, Giovannini M, Ma B. Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts. Cancer Sci. 2020 Feb;111(2):536-547. doi: 10.1111/cas.14254. Epub 2019 Dec 30. PMID: 31778267; PMCID: PMC7004521. 12: Qin S, Chan SL, Sukeepaisarnjaroen W, Han G, Choo SP, Sriuranpong V, Pan H, Yau T, Guo Y, Chen M, Ren Z, Xu J, Yen CJ, Lin ZZ, Manenti L, Gu Y, Sun Y, Tiedt R, Hao L, Song W, Tanwandee T. A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma. Ther Adv Med Oncol. 2019 Dec 11;11:1758835919889001. doi: 10.1177/1758835919889001. Erratum in: Ther Adv Med Oncol. 2020 Mar 12;12:1758835920913426. PMID: 31853265; PMCID: PMC6906348. 13: Going After METex14 in NSCLC. Cancer Discov. 2019 Aug;9(8):OF9. doi: 10.1158/2159-8290.CD-ND2019-006. Epub 2019 Jun 17. PMID: 31209157. 14: Shaker ME, Ashamallah SA, El-Mesery M. The novel c-Met inhibitor capmatinib mitigates diethylnitrosamine acute liver injury in mice. Toxicol Lett. 2016 Nov 2;261:13-25. doi: 10.1016/j.toxlet.2016.08.015. Epub 2016 Aug 21. PMID: 27553677. 15: Bouattour M, Raymond E, Qin S, Cheng AL, Stammberger U, Locatelli G, Faivre S. Recent developments of c-Met as a therapeutic target in hepatocellular carcinoma. Hepatology. 2018 Mar;67(3):1132-1149. doi: 10.1002/hep.29496. Epub 2018 Feb 1. PMID: 28862760; PMCID: PMC5873445. 16: Li H, Li CW, Li X, Ding Q, Guo L, Liu S, Liu C, Lai CC, Hsu JM, Dong Q, Xia W, Hsu JL, Yamaguchi H, Du Y, Lai YJ, Sun X, Koller PB, Ye Q, Hung MC. MET Inhibitors Promote Liver Tumor Evasion of the Immune Response by Stabilizing PDL1. Gastroenterology. 2019 May;156(6):1849-1861.e13. doi: 10.1053/j.gastro.2019.01.252. Epub 2019 Jan 31. PMID: 30711629; PMCID: PMC6904924. 17: Saad KM, Shaker ME, Shaaban AA, Abdelrahman RS, Said E. The c-Met inhibitor capmatinib alleviates acetaminophen-induced hepatotoxicity. Int Immunopharmacol. 2020 Apr;81:106292. doi: 10.1016/j.intimp.2020.106292. Epub 2020 Feb 14. PMID: 32062076. 18: Reungwetwattana T, Liang Y, Zhu V, Ou SI. The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The Why, the How, the Who, the Unknown, and the Inevitable. Lung Cancer. 2017 Jan;103:27-37. doi: 10.1016/j.lungcan.2016.11.011. Epub 2016 Nov 15. PMID: 28024693. 19: Gautschi O, Menon R, Bertrand M, Murer C, Diebold J. Capmatinib and Osimertinib Combination Therapy for EGFR-Mutant Lung Adenocarcinoma. J Thorac Oncol. 2020 Jan;15(1):e13-e15. doi: 10.1016/j.jtho.2019.07.027. PMID: 31864554. 20: Schuler M, Berardi R, Lim WT, de Jonge M, Bauer TM, Azaro A, Gottfried M, Han JY, Lee DH, Wollner M, Hong DS, Vogel A, Delmonte A, Akimov M, Ghebremariam S, Cui X, Nwana N, Giovannini M, Kim TM. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial. Ann Oncol. 2020 Mar 30:S0923-7534(20)36380-8. doi: 10.1016/j.annonc.2020.03.293. Epub ahead of print. PMID: 32240796.

Product Data:
Biological target: ATP competitive c-Met kinase inhibitor (IC50=0.13 nM).
In vitro activity: Pancreatic cancer is characterized by a strong stromal reaction. Therefore, the effects of cMET inhibition on ECs and VSMCs were examined. MTT assays in ECs under serum-starved conditions and stimulation with HGF, showed a slight but significant increase in growth that was diminished by INC280 (Capmatinib) (Additional file 3: Figure S3B). No effect upon constitutive conditions was observed (Additional file 3: Figure S3A). EC motility was significantly increased upon incubation with HGF, which was strongly reduced by INC280 (Figure 4A). Regarding activation of signaling pathways, treatment with INC280 strongly inhibited HGF-induced activation of Akt and ERK whereas no effects on constitutive Akt and ERK phosphorylation were found (Figure 4B). Taken together, these results show that INC280 affects ECs only when these cells are stimulated with HGF. Next we analyzed the impact of INC280 on VSMCs. MTT assays showed a dose-dependent inhibition of VSMC growth starting from INC280 (100nM) after 72 hours of incubation (Additional file 3: Figure S3C). In contrast to ECs, stimulation with HGF upon serum-starved conditions had no effect on VSMC growth and, accordingly, INC280 did not have a further growth inhibitory effect in MTT assays (Additional file 3: Figure S3D). Motility upon incubation with HGF in VSMCs was not induced, but targeting cMET with INC280 led to a significant inhibition of constitutive migration (Figure 4C). Finally, Western blotting did not show a substantial effect of INC280 on constitutive Akt phosphorylation and only a minor impact on ERK phosphorylation in VSMCs (Figure 4D). These results indicate that HGF does not affect VSMCs and cMET inhibition with INC280, therefore, has only minor effects on these cells. Reference: BMC Cancer. 2015; 15: 71.
In vivo activity: Tumors underwent a histological examination by a pathologist to determine phenotype and progression. Of the WT mice fed normal diet there were a total of 16 tumors. Twelve of the tumors were papillomas, with one converting to a squamous cell carcinoma (Fig.4d). Three additional tumors were cutaneous lipomas. This is in comparison to Tpl2 −/− mice which had a total of 61 tumors, 51 papillomas, four SCCs, three sebaceous adenomas, and three lipomas. In contrast, no Tpl2 −/− mice fed capmatinib diet had papillomas convert to SCCs (Fig. (Fig.4d).4d). Although Tpl2 −/− mice develop an overall higher tumor burder, there were no statistical differences in tumor size between genotypes and the rate of malignant conversion (7.8 vs. 8.3%) was similar between Tpl2 −/− and WT mice on normal diet. However, the rate of malignant conversion between Tpl2 −/− mice on normal diet (8.3%) vs. Tpl2 −/− mice on Capmatinib diet (0%) was significantly different (p < 0.01). In both genotypes male mice developed more tumors than female mice (Fig.4e; p < 0.05). Reference: Oncogenesis. 2019 Jan; 8(1): 1.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Soluble in DMSO 0.0 0.00

Preparing Stock Solutions

The following data is based on the product molecular weight 503.36 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. Brandes F, Schmidt K, Wagner C, Redekopf J, Schlitt HJ, Geissler EK, Lang SA. Targeting cMET with INC280 impairs tumour growth and improves efficacy of gemcitabine in a pancreatic cancer model. BMC Cancer. 2015 Feb 19;15:71. doi: 10.1186/s12885-015-1064-9. PMID: 25884642; PMCID: PMC4340491.
In vivo protocol: 1. Bonan NF, Kowalski D, Kudlac K, Flaherty K, Gwilliam JC, Falkenberg LG, Maradiaga E, DeCicco-Skinner KL. Inhibition of HGF/MET signaling decreases overall tumor burden and blocks malignant conversion in Tpl2-related skin cancer. Oncogenesis. 2019 Jan 10;8(1):1. doi: 10.1038/s41389-018-0109-8. PMID: 30631034; PMCID: PMC6328619.

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1: Paik PK, Goyal RK, Cai B, Price MA, Davis KL, Ansquer VD, Caro N, Saliba TR. Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib. Future Oncol. 2023 Feb 7. doi: 10.2217/fon-2022-1133. Epub ahead of print. PMID: 36749292.

2: Yang M, Vioix H, Sachdev R, Stargardter M, Tosh J, Pfeiffer BM, Paik PK. Cost-Effectiveness of Tepotinib versus Capmatinib for the Treatment of Adult Patients with Metastatic Non-Small Cell Lung Cancer Harboring Mesenchymal- epithelial Transition Exon 14 (METex14) Skipping. Value Health. 2022 Dec 8:S1098-3015(22)04750-7. doi: 10.1016/j.jval.2022.11.018. Epub ahead of print. PMID: 36503033.

3: Zayed A, Jaber SA, Al Hroot J, Hawamdeh S, Ayoub NM, Qinna NA. HPLC with Fluorescence and Photodiode Array Detection for Quantifying Capmatinib in Biological Samples: Application to In Vivo and In Vitro Studies. Molecules. 2022 Dec 5;27(23):8582. doi: 10.3390/molecules27238582. PMID: 36500674; PMCID: PMC9738601.

4: Turpin A, Descarpentries C, Grégoire V, Farchi O, Cortot AB, Jamme P. Response to Capmatinib in a MET Fusion-positive Cholangiocarcinoma. Oncologist. 2023 Jan 18;28(1):80-83. doi: 10.1093/oncolo/oyac194. PMID: 36434677; PMCID: PMC9847551.

5: Choi W, Jeong KC, Park SY, Kim S, Kang EH, Hwang M, Han JY. MYC amplification-conferred primary resistance to capmatinib in a MET-amplified NSCLC patient: a case report. Transl Lung Cancer Res. 2022 Sep;11(9):1967-1972. doi: 10.21037/tlcr-22-176. PMID: 36248327; PMCID: PMC9554684.

6: Tseng LW, Chang JW, Wu CE. Safety of Tepotinib Challenge after Capmatinib- Induced Pneumonitis in a Patient with Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation: A Case Report. Int J Mol Sci. 2022 Oct 5;23(19):11809. doi: 10.3390/ijms231911809. PMID: 36233109; PMCID: PMC9570266.

7: Bhangare D, Rajput N, Jadav T, Sahu AK, Sengupta P. Mechanism of capmatinib degradation in stress conditions including degradation product characterization using ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry and stability-indicating analytical method development. Rapid Commun Mass Spectrom. 2023 Jan 15;37(1):e9417. doi: 10.1002/rcm.9417. PMID: 36226771.

8: Wilgucki M, Yeung V, Ho G, Bravo Montenegro GL, Jones G, Reuss JE, Liu SV, Kim C. Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report. JTO Clin Res Rep. 2022 Aug 5;3(10):100396. doi: 10.1016/j.jtocrr.2022.100396. PMID: 36188633; PMCID: PMC9516460.

9: Chen X, Isambert N, López-López R, Giovannini M, Pognan N, Kapoor S, Quinlan M, You B, Cui X, Rahmanzadeh G, Mau-Sorensen M. Effect of capmatinib on the pharmacokinetics of substrates of CYP3A (midazolam) and CYP1A2 (caffeine) in patients with MET-dysregulated solid tumours. Br J Clin Pharmacol. 2023 Mar;89(3):1046-1055. doi: 10.1111/bcp.15544. Epub 2022 Oct 17. PMID: 36131603.

10: Cui X, Chen X, Pognan N, Sengupta T, Rahmanzadeh G, Kornberger R, Giovannini M. Evaluation of the Pharmacokinetic Drug Interaction of Capmatinib With Itraconazole and Rifampicin and Potential Impact on Renal Transporters in Healthy Subjects. J Clin Pharmacol. 2023 Feb;63(2):228-238. doi: 10.1002/jcph.2153. Epub 2022 Nov 2. PMID: 36087217.

11: Kim TW, Lee KM, Lee SH. Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System Metastasis. Onco Targets Ther. 2022 Aug 31;15:941-946. doi: 10.2147/OTT.S382722. PMID: 36072511; PMCID: PMC9441579.

12: Lin CY, Wei SH, Chen YL, Lee CT, Wu SY, Ho CL, Pavlick DC, Su PL, Lin CC. Case report: Salvage capmatinib therapy in KIF5B-MET fusion-positive lung adenocarcinoma with resistance to telisotuzumab vedotin. Front Oncol. 2022 Aug 11;12:919123. doi: 10.3389/fonc.2022.919123. PMID: 36033470; PMCID: PMC9404301.

13: Illini O, Fabikan H, Swalduz A, Vikström A, Krenbek D, Schumacher M, Dudnik E, Studnicka M, Öhman R, Wurm R, Wannesson L, Peled N, Kian W, Bar J, Daher S, Addeo A, Rotem O, Pall G, Zer A, Saad A, Cufer T, Sorotsky HG, Hashemi SMS, Mohorcic K, Stoff R, Rovitsky Y, Keren-Rosenberg S, Winder T, Weinlinger C, Valipour A, Hochmair MJ. Real-world experience with capmatinib in MET exon 14-mutated non-small cell lung cancer (RECAP): a retrospective analysis from an early access program. Ther Adv Med Oncol. 2022 Jun 13;14:17588359221103206. doi: 10.1177/17588359221103206. PMID: 35720834; PMCID: PMC9201318.

14: Fujino T, Suda K, Koga T, Hamada A, Ohara S, Chiba M, Shimoji M, Takemoto T, Soh J, Mitsudomi T. Foretinib can overcome common on-target resistance mutations after capmatinib/tepotinib treatment in NSCLCs with MET exon 14 skipping mutation. J Hematol Oncol. 2022 Jun 11;15(1):79. doi: 10.1186/s13045-022-01299-z. PMID: 35690785; PMCID: PMC9188708.

15: Brazel D, Zhang S, Nagasaka M. Spotlight on Tepotinib and Capmatinib for Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation. Lung Cancer (Auckl). 2022 May 13;13:33-45. doi: 10.2147/LCTT.S360574. PMID: 35592355; PMCID: PMC9113513.

16: Park HS, Abd El-Aty AM, Jeong JH, Lee T, Jung TW. Capmatinib suppresses LPS- induced interaction between HUVECs and THP-1 monocytes through suppression of inflammatory responses. Biomed J. 2022 Apr 26:S2319-4170(22)00071-3. doi: 10.1016/ Epub ahead of print. PMID: 35483573.

17: Chou YT, Lin CC, Lee CT, Pavlick DC, Su PL. Durable Response of Dabrafenib, Trametinib, and Capmatinib in an NSCLC Patient With Co-Existing BRAF-KIAA1549 Fusion and MET Amplification: A Case Report. Front Oncol. 2022 Mar 18;12:838798. doi: 10.3389/fonc.2022.838798. PMID: 35372088; PMCID: PMC8972191.

18: Hashiguchi MH, Sato T, Yamamoto H, Watanabe R, Kagyo J, Domoto H, Shiomi T. Successful Tepotinib Challenge After Capmatinib-Induced Interstitial Lung Disease in a Patient With Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation: Case Report. JTO Clin Res Rep. 2021 Dec 28;3(2):100271. doi: 10.1016/j.jtocrr.2021.100271. PMID: 35252894; PMCID: PMC8888201.

19: Lefler DS, Tierno MB, Bashir B. Partial treatment response to capmatinib in MET-amplified metastatic intrahepatic cholangiocarcinoma: case report & review of literature. Cancer Biol Ther. 2022 Dec 31;23(1):112-116. doi: 10.1080/15384047.2022.2029128. PMID: 35129063; PMCID: PMC8820818.

20: Guo MZ, Marrone KA, Spira A, Waterhouse DM, Scott SC. Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics. Onco Targets Ther. 2021 Nov 23;14:5321-5331. doi: 10.2147/OTT.S273357. PMID: 34853516; PMCID: PMC8627896.