[CAS NO. 1197376-85-4] Capmatinib dihydrochloride
PRODUCTS SPECIFICATIONS [1197376-85-4]
DESCRIPTION [1197376-85-4]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 485.34 |
| Molecular Formula | C23H19Cl2FN6O |
| SMILES | O=C(NC)C1=CC=C(C2=NN3C(N=C2)=NC=C3CC4=CC=C5N=CC=CC5=C4)C=C1F.Cl.Cl |
6 Publications Citing Use of MCE
Summary
Capmatinib (INC280; INCB28060) dihydrochloride is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor ( IC 50 =0.13 nM). Capmatinib dihydrochloride can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT , FAK , GAB1, and STAT3/5. Capmatinib dihydrochloride potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis . Antitumor activity. Capmatinib dihydrochloride is largely metabolized by CYP3A4 and aldehyde oxidase [1] [2] [3] .
IC50 & Target
IC 50 : 0.13 nM (c-MET) [1]
In Vitro
Capmatinib (INCB28060) inhibits c-MET phosphorylation with an IC
50
value of approximately 1 nM and a concentration of approximately 4 nM inhibits c-MET more than 90%, which is reversible and the effect is significantly reduced in several hours after the compound is removed and completely disappeared by 48 hours
[1]
.
Capmatinib (INCB28060) (0-10000 nM; 72 h) inhibits the proliferation of SNU-5, S114, H441 and U-87MG
[1]
.
Capmatinib (INCB28060) (0.06-62.25 nM; 2h) effectively inhibits phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5
[1]
.
Capmatinib (INCB28060) (0.24-63 nM; over night) prevents HGF-stimulated H441 cell migration
[1]
.
Capmatinib (INCB28060) (0.5-50 nM; 20 min) suppresses phosphorylation of both EGFR and HER-3 rapidly
[1]
.
Capmatinib (INCB28060) (0-333 nM; 24 h) induces apoptosis in SNU-5 cells
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| Cell Line: | SNU-5, S114, H441 and U-87MG |
| Concentration: | 0-10000 nM |
| Incubation Time: | 72 h |
| Result: | Inhibited the cell viability of SNU-5 and S114, as well as the colony formation of H441 and U-87MG, with IC 50 values of 1.2 nM, 12.4 nM, ~0.5 nM and 2 nM, respectively. |
Cell Migration Assay [1]
| Cell Line: | H441 (stimulated with 50 ng/mL recombinant human HGF for 24h) |
| Concentration: | 0.24, 1, 4, 16 and 63 nM |
| Incubation Time: | Over night |
| Result: | Prevented HGF-stimulated H441 cell migration, with IC 50 of approximately 2 nM, and less cell migration at 16 nM. |
Western Blot Analysis [1]
| Cell Line: | SNU-5 |
| Concentration: | 0.06, 0.24, 0.98, 3.91, 15.63 and 62.25 nM |
| Incubation Time: | 2 h |
| Result: | Effectively inhibited phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. |
Western Blot Analysis [1]
| Cell Line: | H1993 cells |
| Concentration: | 0.5, 5 and 50 nM |
| Incubation Time: | 20 min |
| Result: | Suppressed phosphorylation of both EGFR and HER-3 rapidly and as effectively as the compound inhibited c-MET phosphorylation in H1993 cells. |
Apoptosis Analysis [1]
| Cell Line: | SNU-5 cells |
| Concentration: | 0.017, 0.15, 1.37, 12.33, 111 and 333 nM |
| Incubation Time: | 24 h |
| Result: | Effectively induced DNA fragmentation. |
In Vivo
Capmatinib (INCB28060) (1-30 mg/kg; PO, twice daily, for 2 weeks) exhibits dose-dependent inhibition of tumor growth, and shows well tolerance at all doses during the treatment periods, with no evidence of overt toxicity or weight loss in U-87MG tumor mice model
[1]
.
Capmatinib (INCB28060) (0.03-10 mg/kg; PO, single dosage) causes inhibition of c-MET phosphorylation in S114 tumor mice model
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female Balb/c nu/nu mice (inoculated subcutaneously with 5×10 6 U-87MG glioblastoma cells) [1] |
| Dosage: | 1, 3, 10 and 30 mg/kg |
| Administration: | PO, twice daily, for 2 weeks |
| Result: | Exhibited dose-dependent inhibition of tumor growth with 35% and 76% at 1 and 3 mg/kg once daily; resulted in partial regressions in 6 of 10 U-87MG tumor-bearing mice at 10 mg/kg once daily; and showed well tolerance at all doses during the treatment periods, with no evidence of overt toxicity or weight loss. |
| Animal Model: | Female Balb/c nu/nu mice (inoculated subcutaneously with 4×10 6 S114 tumor cells) [1] |
| Dosage: | 0.03, 0.1, 0.3, 1, 3 and 10 mg/kg |
| Administration: | PO, single dosage |
| Result: | Caused approximately 50% and 90% inhibition of c-MET phosphorylation at 0.03 and 0.3 mg/kg after administration of 30 min, and inhibition of phospho-c-MET exceeded 90% after 7 hours. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT05488314 | Janssen Research & Development, LLC |
Carcinoma, Non-Small-Cell Lung
|
November 28, 2022 | Phase 2 |
| NCT01546428 | Novartis Pharmaceuticals|Novartis |
Advanced Solid Tumor
|
February 2012 | Phase 1 |
| NCT02626234 | Novartis Pharmaceuticals|Novartis |
cMET-dysregulated Advanced Solid Tumors
|
December 8, 2015 | Phase 1 |
| NCT04427072 | Novartis Pharmaceuticals|Novartis |
Carcinoma, Non-Small-Cell Lung
|
September 25, 2020 | Phase 3 |
| NCT05110196 | Novartis Pharmaceuticals|Novartis |
Non-Small Cell Lung Carcinoma
|
September 3, 2022 | Phase 4 |
| NCT02323126 | Novartis Pharmaceuticals|Novartis |
Non Small Cell Lung Cancer
|
February 9, 2015 | Phase 2 |
| NCT03484923 | Novartis Pharmaceuticals|Novartis |
Melanoma
|
September 10, 2018 | Phase 2 |
| NCT04741789 | Novartis Pharmaceuticals|Novartis |
Carcinoma, Non-Small Cell Lung|Non-Small Cell Lung Cancer|Non-Small-Cell Lung Carcinoma|Nonsmall Cell Lung Cancer
|
||
| NCT02795429 | Novartis Pharmaceuticals|Novartis |
Advanced Hepatocellular Carcinoma
|
June 15, 2016 | Phase 1|Phase 2 |
| NCT03040973 | Novartis Pharmaceuticals|Novartis |
Advanced Solid Tumors Which Are cMET-dependent
|
July 4, 2017 | Phase 2 |
| NCT02750215 | Massachusetts General Hospital|Novartis |
Malignant Non-small Cell Neoplasm of Lung Stage IV
|
May 2016 | Phase 2 |
| NCT04677595 | Novartis Pharmaceuticals|Novartis |
Non-Small Cell Lung Cancer (NSCLC)
|
May 17, 2021 | Phase 2 |
| NCT01737827 | Novartis Pharmaceuticals|Novartis |
Advanced Hepatocellular Carcinoma With c-MET Dysregulation
|
March 25, 2013 | Phase 2 |
| NCT02205398 | Novartis Pharmaceuticals|Novartis |
Squamous Cell Carcinoma of Head and Neck (SCCHN)|Metastatic Colorectal Cancer
|
July 28, 2014 | Phase 1 |
| NCT03333343 | Novartis Pharmaceuticals|Novartis |
EGFR-mutant Non-small Cell Lung Cancer
|
January 29, 2018 | Phase 1 |
| NCT03742349 | Novartis Pharmaceuticals|Novartis |
Triple Negative Breast Cancer (TNBC)
|
January 31, 2019 | Phase 1 |
| NCT03240393 | Novartis Pharmaceuticals|Novartis |
Carcinoma|Non-Small-Cell Lung Cancer
|
July 31, 2018 | Phase 2 |
| NCT05243641 | M.D. Anderson Cancer Center|Celcuity, Inc.|Novartis|Puma Biotechnology, Inc. |
Metastatic Breast Cancer|Breast Cancer
|
August 18, 2022 | Phase 1|Phase 2 |
| NCT04460729 | Novartis Pharmaceuticals|Novartis |
Non-small Cell Lung Carcinoma (NSCLC)
|
November 11, 2020 | Phase 2 |
| NCT04139317 | Novartis Pharmaceuticals|Novartis |
Non-small Cell Lung Cancer (NSCLC)
|
January 22, 2020 | Phase 2 |
| NCT02587650 | University of California, San Francisco |
ALK Fusion Protein Expression|BRAF wt Allele|Invasive Skin Melanoma|MET Fusion Gene Positive|NRAS wt Allele|NTRK1 Fusion Positive|NTRK2 Fusion Positive|NTRK3 Fusion Positive|RET Fusion Positive|ROS1 Fusion Positive|Stage III Cutaneous Melanoma|Stage IIIA Cutaneous Melanoma|Stage IIIB Cutaneous Melanoma|Stage IIIC Cutaneous Melanoma|Stage IV Cutaneous Melanoma
|
March 26, 2015 | Phase 2 |
| NCT03647488 | Novartis Pharmaceuticals|Novartis |
Carcinoma, Non-Small-Cell Lung
|
December 26, 2018 | Phase 2 |
| NCT02335944 | Novartis Pharmaceuticals|Novartis |
Non Small Cell Lung Cancer
|
January 13, 2015 | Phase 1|Phase 2 |
| NCT04926831 | Novartis Pharmaceuticals|Novartis |
Non-small Cell Lung Cancer
|
August 10, 2022 | Phase 2 |
| NCT01964235 | Novartis Pharmaceuticals|Novartis |
Advanced Hepatocellular Carcinoma
|
December 2016 | Phase 2 |
| NCT05135845 | Assistance Publique - Hôpitaux de Paris |
Oesophageal Adenocarcinoma|Gastric Adenocarcinoma
|
March 22, 2022 | Phase 2 |
| NCT01610336 | Novartis Pharmaceuticals|Novartis |
Non-small Cell Lung Cancer
|
April 5, 2012 | Phase 2 |
| NCT01911507 | University of California, Davis|Novartis Pharmaceuticals|National Cancer Institute (NCI) |
Recurrent Non-small Cell Lung Cancer
|
August 27, 2013 | Phase 1 |
| NCT02414139 | Novartis Pharmaceuticals|Novartis |
Carcinoma, Non-Small-Cell Lung
|
June 11, 2015 | Phase 2 |
| NCT05435846 | Collin Blakely|Novartis|University of California, San Francisco |
Metastatic Lung Non-Small Cell Carcinoma|Stage IV Lung Cancer
|
August 10, 2022 | Phase 1 |
| NCT02276027 | Novartis Pharmaceuticals|Novartis |
Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma
|
January 20, 2015 | Phase 2 |
| NCT02468661 | Novartis Pharmaceuticals|Novartis |
Non-Small Cell Lung Cancer
|
September 23, 2015 | Phase 1 |
| NCT02019693 | National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) |
Kidney Cancer
|
January 24, 2014 | Phase 2 |
| NCT02474537 | Novartis Pharmaceuticals|Novartis |
Hepatic Impairment
|
June 12, 2015 | Phase 1 |
| NCT04323436 | Novartis Pharmaceuticals|Novartis |
Carcinoma, Non-Small-Cell Lung
|
August 19, 2020 | Phase 2 |
| NCT01324479 | Novartis Pharmaceuticals|Novartis |
Solid Tumors
|
February 29, 2012 | Phase 1 |
| NCT04816214 | Novartis Pharmaceuticals|Novartis |
Carcinoma, Non-Small-Cell Lung
|
September 22, 2021 | Phase 3 |
| NCT02925104 | Novartis Pharmaceuticals|Novartis |
cMET Dysegulation Advanced Solid Tumors
|
December 14, 2016 | Phase 1 |
| NCT02159066 | Pfizer |
Melanoma
|
July 23, 2014 | Phase 2 |
| NCT03693339 | Asan Medical Center |
Cancer|Lung Cancer Metastatic|MET Gene Mutation
|
October 30, 2018 | Phase 2 |
| NCT05154344 | Intergroupe Francophone de Cancerologie Thoracique|Novartis |
MET Alterations|Non Small Cell Lung Cancer|METex14 Mutations
|
November 29, 2021 | |
| NCT02520752 | Novartis Pharmaceuticals|Novartis |
cMET-dysregulated Advanced Solid Tumors
|
December 10, 2015 | Phase 1 |
| NCT03784014 | Institut National de la Santé Et de la Recherche Médicale, France|Commissariat A L´energie Atomique|Institut Bergonié|Plateforme labellisée Inca - Institut Bergonié, Bordeaux|Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris|EUCLID Clinical Trial Platform |
Soft Tissue Sarcoma
|
October 19, 2019 | Phase 3 |
| NCT05567055 | Timothy Burns|Novartis|University of Pittsburgh |
Non-small Cell Lung Cancer
|
December 2022 | Phase 2 |
| NCT01870726 | Novartis Pharmaceuticals|Novartis |
c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM
|
January 9, 2014 | Phase 1|Phase 2 |
| NCT02386826 | SCRI Development Innovations, LLC|Novartis |
Glioblastoma Multiforme|Gliosarcoma|Colorectal Cancer|Renal Cell Carcinoma
|
September 22, 2015 | Phase 1 |
Shipping
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
References
- [1] Liu X, et al. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clin Cancer Res. 2011 Nov 15;17(22):7127-38.
- [2] Baltschukat S, et al. 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.
- [3] Dhillon S. Capmatinib: First Approval. Drugs. 2020 Jul;80(11):1125-1131.