CAPMATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H17FN6O
Molecular Weight	412.4191
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)C1=CC=C(C=C1F)C2=NN3C(CC4=CC=C5N=CC=CC5=C4)=CN=C3N=C2

InChI

InChIKey=LIOLIMKSCNQPLV-UHFFFAOYSA-N

InChI=1S/C23H17FN6O/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)

HIDE SMILES / InChI

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=666907
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800031741

Capmatinib (INC280, INCB028060), is an orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. Novartis acquired Incyte's capmatinib, which is in Phase II clinical trial as monotherapy in patients with advanced hepatocellular carcinoma. Capmatinib 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. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21918175	Inhibitor 8297		0.13 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT02414139	Primary	Phase II 1132	Unknown Approved Use Unknown
Melanoma 88 Sources: https://clinicaltrials.gov/ct2/show/NCT02159066	Primary	Phase II 1132	Unknown Approved Use Unknown
Advanced hepatocellular carcinoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02795429	Primary	Phase II 1132	Unknown Approved Use Unknown
Papillary renal cell carcinoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02019693	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
6450 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30724423	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CAPMATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
26300 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30724423	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CAPMATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30724423	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CAPMATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 2 times / day steady, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	unhealthy, 56.0 years n = 8 Health Status: unhealthy Age Group: 56.0 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	Other AEs: ALT increased, Nausea... Other AEs: ALT increased (grade 3-4, 13%) Nausea (grade 1-2, 38%) Vomiting (grade 1-2, 38%) AST increased (grade 1-2, 25%) Blood bilirubin increased (grade 1-2, 13%) Fatigue (grade 1-2, 38%) Decreased appetite (grade 1-2, 38%) Peripheral edema (grade 1-2, 13%) Hypoalbuminemia (grade 1-2, 13%) Diarrhea (grade 1-2, 25%) Protein total decreased (grade 1-2, 13%) Stomatitis (grade 1-2, 13%) Dyspepsia (grade 1-2, 13%) Sources: https://pubmed.ncbi.nlm.nih.gov/31778267
200 mg 2 times / day steady, oral Studied dose Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	unhealthy, 56.0 years n = 5 Health Status: unhealthy Age Group: 56.0 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31778267
250 mg 2 times / day steady, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: steady Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	unhealthy, 56.0 years n = 4 Health Status: unhealthy Age Group: 56.0 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	DLT: Blood bilirubin increased... Dose limiting toxicities: Blood bilirubin increased (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31778267
450 mg 2 times / day steady, oral Studied dose Dose: 450 mg, 2 times / day Route: oral Route: steady Dose: 450 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	unhealthy, 56.0 years n = 9 Health Status: unhealthy Age Group: 56.0 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/31778267	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31778267
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213591s000lbl.pdf	unhealthy, 71 years (range: 49 - 90 years) n = 334 Health Status: unhealthy Condition: Non-Small Cell Lung Cancer Age Group: 71 years (range: 49 - 90 years) Sex: M+F Population Size: 334 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213591s000lbl.pdf	Disc. AE: Peripheral edema, Pneumonitis... AEs leading to discontinuation/dose reduction: Peripheral edema (all grades, 1.8%) Pneumonitis (all grades, 1.8%) Fatigue (all grades, 1.5%) Peripheral edema (>2) Blood creatinine increased (>2) Nausea (>2) Vomiting (>2) Lipase increased (>2) ALT increased (>2) Dyspnea (>2) Amylase increased (>2) AST increased (>2) Blood bilirubin increased (>2) Fatigue (>2) Pneumonia (>2) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213591s000lbl.pdf
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: p. 135	unhealthy, 71 years (range: 49 - 90 years) n = 334 Health Status: unhealthy Condition: Non-Small Cell Lung Cancer Age Group: 71 years (range: 49 - 90 years) Sex: M+F Population Size: 334 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: p. 135	Disc. AE: Peripheral edema, Pneumonitis... AEs leading to discontinuation/dose reduction: Peripheral edema (grade 3-4, 0.6%) Pneumonitis (grade 3-4, 0.3%) Fatigue (grade 3-4, 0.9%) ALT increased (all grades, 0.9%) ALT increased (grade 3-4, 0.6%) AST increased (all grades, 0.9%) AST increased (grade 3-4, 0.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: p. 135

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 inducer 389		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 P-gp 1461 OCT1 512 OAT1 599 OAT3 642 OATP1B1 788 BCRP 699 MATE1 306 MATE2 263 CYP3A 214 OATP1B3 706 BSEP 402 MRP2 383	aldehyde oxidase 16 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88, 200, 202	weak [Ki 0.9 uM]		likely Comment: capmatinib was predicted to be a weak CYP2C8 inhibitor with 23% increase in Cmax and 39% increase in AUC of repaglinide Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88, 200, 202
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 200, 202	yes [EC50 39.4 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88, 200	yes [Ki 0.28 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88, 200	yes [Ki 0.29 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 200, 202	yes [Ki 3 uM]		unlikely Comment: no significant exposure change was predicted for warfarin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 200, 202
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 87, 200, 202	yes [Ki 4.3 uM]		no (co-administration study) Comment: In subjects with cancer, co-administration of midazolam (a sensitive CYP3A4 substrate) with multiple doses of capmatinib (400 mg b.i.d.) did not cause any clinically significant increase in midazolam exposure compared to administration of midazolam alone. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 87, 200, 202
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 200, 202	yes [Ki 6.1 uM]		unlikely Comment: no significant exposure change was predicted for omeprazole Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 200, 202
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes	CMN288 3
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes	CMN288 3
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes	CMN288 3
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 200.0	yes
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88, 200	yes		yes (co-administration study) Comment: coadministration with rosuvastatin increased rosuvastatin AUC by 108% and Cmax by 204% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88, 200
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88	yes		yes (co-administration study) Comment: coadministration with digoxin increased digoxin AUC by 47% and Cmax by 74% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 86, 88

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 201.0	yes
aldehyde oxidase 16	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 75.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 66, 75, 83, 85	yes	yes (co-administration study) Comment: itraconazole increased capmatinib exposure 42%; rifampicin decreased capmatinib exposure by 67% and Cmax by 56% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 66, 75, 83, 85

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213591Orig1s000MultidisciplineR.pdf Page: 32, 41

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34099	https://www.001chemical.com/chem/1029712-80-8
AA Blocks	AA003A97	https://www.aablocks.com/goods/Goods/detail?id=AA003A97
AK Scientific, Inc. (AKSCI)	Y0337	http://www.aksci.com/item_detail.php?cat=Y0337
Aaron Chemicals	AR003B0Z	http://www.aaronchem.com/1029712-80-8
AbMole Bioscience	M2080	http://www.abmole.com/products/incb28060.html
Acadechem	ACDS-070219	http://www.acadechemical.com/product/144918
Acorn PharmaTech	ACN-050758	http://www.acornpharmatech.com/
Active Biopharma	ABP000812	http://www.activebiopharma.com/1029712-80-8
Adooq BioScience	A11132	https://www.adooq.com/incb28060.html
Alsachim	4808	http://www.alsachim.com/product-C6188-glo.bal-view.html
Ambinter	Amb22170030	http://www.ambinter.com/reference/22170030
Angel Pharmatech	AG-10391	http://www.angelpharmatech.com/1029712-80-8.html
Angene	AGN-PC-04X71V	http://www.angenechemical.com/productshow/AGN-PC-04X71V.html
ApexBio Technology	A8448	http://www.apexbt.com/incb28060.html
Ark Pharm	AK174338	http://www.arkpharminc.com/products/1029712-80-8.html
Aurora Fine Chemicals LLC	K16.647.349	http://online.aurorafinechemicals.com/info?ID=K16.647.349
Aurum Pharmatech LLC	W-5775	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5775
BioChemPartner	BCP23444	http://www.biochempartner.com/1029712-80-8-BCP23444
BioCrick	BCC3793	http://www.biocrick.com/INCB28060-BCC3793.html
BioSynth	J-509516	https://www.biosynth.com/en/products/all-products/products/J-509516.html
Boerchem	BC261868	http://www.boerchem.com/?product_43039.html
Chem Scene	CS-1541	http://www.chemscene.com/1029712-80-8.html
Chemspace	CSSB00015189161	https://chem-space.com/CSSB00015189161
DC Chemicals	DC7167	http://www.dcchemicals.com/product_show-Capmatinib_INCB28060_.html
Debye Scientific	DA-33530	http://www.debyesci.com/cas_1029712-80-8.html
Excenen	EX-A446	http://www.excenen.com/searchresultlist.php?id=1029712-80-8
Finetech	FT-0746310	http://www.finetechnology-ind.com/prod/detail/pub/1029712-80-8.html
Hairui	HR141090	http://www.hairuichem.com/en/product/1029712-80-8.html
Hefei Hirisun Pharmatech Co., Ltd	HR130870	http://hirisunpharm.com/1029712-80-8.html
Lab Network	LN01341861	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341861
Matrix Scientific	145224	https://www.matrixscientific.com/145224.html
MedChem Express	HY-13404	https://www.medchemexpress.com/INCB28060.html
Molcore	MC34099	https://www.molcore.com/product/1029712-80-8
MuseChem	I000180	https://www.musechem.com/product/I000180.html
Renno Tech	RL00142	http://www.rennotech.com/product_show.asp?id=888
Selleck Chemicals	S2788	http://www.selleckchem.com/products/incb28060.html
Sinfoo Biotech	S054562	http://www.sinfoobiotech.com/product/1057960
Smolecule	S547925	http://www.smolecule.com/products/s547925
Smolecule	S746742	https://www.smolecule.com/products/s746742
Synblock Inc	SB16608	http://www.synblock.com/product/1029712-80-8.html
THE BioTek	bt-253455	https://www.thebiotek.com/product/inhibitors/bt-253455
THE BioTek	bt-287203	https://www.thebiotek.com/product/inhibitors/bt-287203
Yuhao Chemical	YH65244	http://www.chemyuhao.com/1029712-80-8.html
abcr GmbH	AB460674	http://www.abcr.com/shop/en/AB460674
eNovation Chemicals	D372424	http://www.enovationchem.com/productDetails.asp?productID=D372424
iChemical	EBD2207157	http://www.ichemical.com/products/1029712-80-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3.	2011 Nov 15	21918175

Patents

Sample Use Guides

In Vivo Use Guide

400 mg twice every day by mouth, continuously

Route of Administration: Oral

In Vitro Use Guide

Capmatinib inhibits c-MET phosphorylation with an IC50 value of approximately 1 nmol/L and a concentration of approximately 4 nmol/ L inhibits c-MET more than 90%.

Name

Type

Language

CAPMATINIB

Official Name

English

CAPMATINIB [USAN]

Common Name

English

INCB-28060 FREE BASE

Code

English

INC280

Code

English

NVP-INC280

Code

English

INC-280

Code

English

Capmatinib [WHO-DD]

Common Name

English

capmatinib [INN]

Common Name

English

CAPMATINIB [MI]

Common Name

English

INCB-28060

Code

English

2-FLUORO-N-METHYL-4-(7-(QUINOLIN-6-YLMETHYL)IMIDAZO(1,2-B)(1,2,4)TRIAZIN-2-YL)BENZAMIDE

Systematic Name

English

BENZAMIDE, 2-FLUORO-N-METHYL-4-(7-(6-QUINOLINYLMETHYL)IMIDAZO(1,2-B)(1,2,4)TRIAZIN-2-YL)-

Systematic Name

English

NVP-INC280-NX

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825