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

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

Molecular Formula	C23H17FN6O
Molecular Weight	412.4191
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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	Inhibitor 8,297		0.13 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206	Primary	Phase II 1,132	Unknown
Melanoma 88	Primary	Phase II 1,132	Unknown
Advanced hepatocellular carcinoma 3	Primary	Phase II 1,132	Unknown
Papillary renal cell carcinoma 3	Primary	Phase II 1,132	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
6450 ng/mL	400 mg 2 times / day steady-state, oral		CAPMATINIB plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
26300 ng × h/mL	400 mg 2 times / day steady-state, oral		CAPMATINIB plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.7 h	400 mg 2 times / day steady-state, oral		CAPMATINIB plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
600 mg 2 times / day steady, oral Highest studied dose	unhealthy, 56.0 years	Other AEs: ALT increased, Nausea...
200 mg 2 times / day steady, oral Studied dose	unhealthy, 56.0 years	DLT: Fatigue...
250 mg 2 times / day steady, oral Studied dose	unhealthy, 56.0 years	DLT: Blood bilirubin increased...
450 mg 2 times / day steady, oral Studied dose	unhealthy, 56.0 years	DLT: Fatigue...
400 mg 2 times / day steady, oral Recommended	unhealthy, 71 years (range: 49 - 90 years)	Disc. AE: Peripheral edema, Pneumonitis...

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AEs

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AE	Significance	Dose	Population
Blood bilirubin increased	grade 1-2, 13%	600 mg 2 times / day steady, oral Highest studied dose	unhealthy, 56.0 years
Dyspepsia	grade 1-2, 13%	600 mg 2 times / day steady, oral Highest studied dose	unhealthy, 56.0 years
Hypoalbuminemia	grade 1-2, 13%	600 mg 2 times / day steady, oral Highest studied dose	unhealthy, 56.0 years
Peripheral edema	grade 1-2, 13%	600 mg 2 times / day steady, oral Highest studied dose	unhealthy, 56.0 years
Protein total decreased	grade 1-2, 13%	600 mg 2 times / day steady, oral Highest studied dose	unhealthy, 56.0 years

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Sourcing

Sourcing

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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
Aaron Chemicals	AR003B0Z	http://www.aaronchem.com/1029712-80-8
abcr GmbH	AB460674	http://www.abcr.com/shop/en/AB460674
AbMole Bioscience	M2080	http://www.abmole.com/products/incb28060.html

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PubMed

Title	Date	PubMed
No data available in table

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%.

Substance Class	Chemical
Record UNII	TY34L4F9OZ
Record Status	`Validated (UNII)`
Record Version

Show entries

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

Showing 1 to 5 of 13 entries

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Classification Tree

Code System

Code

Antineoplastic Protein Inhibitor

NCI_THESAURUS

C129825

Designated/Approved

FDA ORPHAN DRUG

644518

Protein Kinase Inhibitor

NCI_THESAURUS

C1967

Antineoplastic Agent

NCI_THESAURUS

C1742

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Code System

Code

Type

Description

NCI_THESAURUS

C90564

PRIMARY

CAS

1029712-80-8

PRIMARY

SMS_ID

100000166975

PRIMARY

FDA UNII

TY34L4F9OZ

PRIMARY

WIKIPEDIA

Capmatinib

PRIMARY

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Related Record

Type

Details


					4O760K7S7V

MULTIDRUG AND TOXIN EXTRUSION PROTEIN 2-K

TRANSPORTER -> INHIBITOR

Interaction Type:

REVERSIBLE

Amount:


					TY34L4F9OZ

CAPMATINIB

EXCRETED UNCHANGED

Interaction Type:

AMOUNT EXCRETED

Qualification:

FECAL

Amount:

42 % (average)


					6NP3XSMIP3

MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1

TRANSPORTER -> INHIBITOR

Interaction Type:

REVERSIBLE

Amount:


					QA085PMU8Q

HEPATOCYTE GROWTH FACTOR RECEPTOR

TARGET -> INHIBITOR

Amount:


					TY34L4F9OZ

CAPMATINIB

EXCRETED UNCHANGED

Interaction Type:

TRACE AMOUNT

Qualification:

URINE

Amount:

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Type

Details


					9K3JG6H3K5

CMN-290

METABOLITE -> PARENT

Qualification:

PLASMA

Amount:

5.4 % (average)
of the plasma AUC0-12h


					DD8K9FL3YS

CNJ-294

METABOLITE -> PARENT

Qualification:

URINE

Amount:


					Q23BDW2JTT

CJH-800

METABOLITE -> PARENT

Qualification:

FECAL; PLASMA; URINE

Amount:


					FO9P36IJ9K

CMN-288

METABOLITE -> PARENT

Qualification:

URINE

Amount:

2.9 % (average)
of the dose


					QW1AU0DM8Y

CJK-530

METABOLITE -> PARENT

Qualification:

FECAL; PLASMA; URINE

Amount:

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Related Record

Type

Details


					TY34L4F9OZ

CAPMATINIB

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Parameters
Tmax	PHARMACOKINETIC	[1 to 2] hours (average)	IN PATIENTS WITH CANCER ORAL ADMINISTRATION 400 mg (average)

blood-to-plasma ratio	PHARMACOKINETIC	0.9 (average)	at higher concentrations

blood-to-plasma ratio	PHARMACOKINETIC	1.5 (average)

Biological Half-life	PHARMACOKINETIC	6.5 hours (average)

Volume of Distribution	PHARMACOKINETIC	164 LITERS (average)	AT STEADY-STATE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2