Details of the Drug

General Information of Drug (ID: DMYCXKL)

• Drug Name: Capmatinib
• Synonyms: 1029712-80-8; INCB28060; INC-280; INC280; UNII-TY34L4F9OZ; 2-fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide; INC28060; INCB-28060; INCB28060(Capmatinib); NVP-INC280; TY34L4F9OZ; Capmatinib (INCB28060); INCB 28060; 2-Fluoro-N-methyl-4-[7-[(quinolin-6-yl)methyl]imidazo[1,2-b]-[1,2,4]triazin-2-yl]benzamide; BenzaMide, 2-fluoro-N-Methyl-4-[7-(6-quinolinylMethyl)iMidazo[1,2-b][1,2,4]triazin-2-yl]-; C23H17FN6O

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[1]
Hepatocellular carcinoma	2C12.02	Phase 2	[2]
Recurrent glioblastoma	2A00.00	Phase 1	[3]

• Affected Organisms: Humans and other mammals
• ATC Code:
  L01EX17: Capmatinib
  L01EX: Other protein kinase inhibitors
  L01E: PROTEIN KINASE INHIBITORS
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 412.4
  Logarithm of the Partition Coefficient (xlogp); 2.9
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 6-12 h [4]
  Bioavailability: The bioavailability of drug is 46% [4]
  Clearance: The clearance of drug is 24 L/h [5]
  Elimination: Following oral administration of radiolabeled capmatinib, approximately 78% of the radioactivity is recovered in feces, of which ~42% is unchanged parent drug, and 22% is recovered in the urine, of which a negligible amount remains unchanged parent drug [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 6.5 hours [5]
  Metabolism: The drug is metabolized via the CYP3A4 and aldehyde oxidase [5]
  Vd: The volume of distribution (Vd) of drug is 164 L [5]
• Chemical Identifiers:
  Formula: C23H17FN6O
  IUPAC Name: 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide
  Canonical SMILES: CNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F
  InChI: 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)
  InChIKey: LIOLIMKSCNQPLV-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 25145656
  CAS Number: 1029712-80-8
  UNII: TY34L4F9OZ
  DrugBank ID: DB11791
  TTD ID: D07OJZ
  ACDINA ID: D00910
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Modulator	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Non-small-cell lung cancer
• ICD Disease Classification: 2C25.Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Proto-oncogene c-Met (MET)	DTT	MET	1.08E-03	-0.24	-0.4

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Capmatinib

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Brigatinib	DM7W94S	Moderate	Increased metabolism of Capmatinib caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[6]
PF-06463922	DMKM7EW	Major	Increased metabolism of Capmatinib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[6]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Capmatinib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[7]

Coadministration of a Drug Treating the Disease Different from Capmatinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Capmatinib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[8]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Capmatinib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[6]
Arn-509	DMT81LZ	Major	Increased metabolism of Capmatinib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[6]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[6]
ABT-492	DMJFD2I	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by ABT-492.	Bacterial infection [1A00-1C4Z]	[6]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Capmatinib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[6]
MK-8228	DMOB58Q	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by MK-8228.	Cytomegaloviral disease [1D82]	[6]
Eslicarbazepine	DMZREFQ	Major	Increased metabolism of Capmatinib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[6]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Capmatinib caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[6]
Ripretinib	DM958QB	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[8]
MK-1439	DM215WE	Moderate	Increased metabolism of Capmatinib caused by MK-1439 mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[6]
Berotralstat	DMWA2DZ	Major	Decreased clearance of Capmatinib due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[9]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Capmatinib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[10]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Capmatinib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[6]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[11]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[12]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Capmatinib caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[6]
Rucaparib	DM9PVX8	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Rucaparib.	Ovarian cancer [2C73]	[6]
MK-4827	DMLYGH4	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by MK-4827.	Ovarian cancer [2C73]	[6]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Capmatinib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[13]
Relugolix	DMK7IWL	Major	Decreased clearance of Capmatinib due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[14]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Capmatinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[6]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Capmatinib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[15]
Larotrectinib	DM26CQR	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Larotrectinib.	Solid tumour/cancer [2A00-2F9Z]	[6]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[16]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Capmatinib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[6]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of Capmatinib due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[17]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Crospovidone	E00626	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Capmatinib eq 150mg base tablet	eq 150mg base	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031741)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Clin Cancer Res. 2015 Nov 1;21(21):4760-6. doi: 10.1158/1078-0432.CCR-15-1185. Epub 2015 Aug 31.
• [5] FDA Approved Drug Products: Tabrecta (capmatinib) oral tablets
• [6] Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
• [7] Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
• [8] Cerner Multum, Inc. "Australian Product Information.".
• [9] Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
• [10] Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
• [11] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [12] Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
• [13] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [14] Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
• [15] Jerntorp P, Almer LO "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand 656 (1981): 33-6. [PMID: 6953748]
• [16] EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
• [17] Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.