Details of the Drug

General Information of Drug (ID: DMSTA36)

• Drug Name: Intedanib
• Synonyms: Nintedanib; Vargatef; 656247-17-5; BIBF-1120; BIBF 1120; 928326-83-4; BIBF1120; Nintedanib (BIBF 1120); OFEV; UNII-G6HRD2P839; (Z)-methyl 3-((4-(N-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenylamino)(phenyl)methylene)-2-oxoindoline-6-carboxylate; G6HRD2P839; CHEBI:85164; 1160294-26-7; Methyl (3z)-3-{[(4-{methyl[(4-Methylpiperazin-1-Yl)acetyl]amino}phenyl)amino](Phenyl)methylidene}-2-Oxo-2,3-Dihydro-1h-Indole-6-Carboxylate

Indication

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Approved	[1]
Idiopathic pulmonary fibrosis	CB03.4	Approved	[2]
Mesothelioma	2C51.2	Phase 3	[3]
Non-small-cell lung cancer	2C25.Y	Phase 3	[4], [5], [6]
Ovarian cancer	2C73	Phase 2	[4], [7]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 539.6
  Topological Polar Surface Area (xlogp); 4.3
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Bioavailability: The bioavailability of drug is 4.7% [8]
  Clearance: The renal clearance of drug is 20 mL/min [9]
  Elimination: Nintedanib is eliminated primarily via fecal and biliary excretion, with 93.4% of radio labelled nintedanib found in feces within 120 hours following administration [9]
  Half-life: The concentration or amount of drug in body reduced by one-half in 10 - 15 hours [10]
  Metabolism: The drug is metabolized via the hydrolytic cleavage by esterases to its principle metabolite BIBF 1202 [8]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [11]
  Vd: The volume of distribution (Vd) of drug is 1050 L [8]
• Chemical Identifiers:
  Formula: C31H33N5O4
  IUPAC Name: methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate
  Canonical SMILES: CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O
  InChI: InChI=1S/C31H33N5O4/c1-34-15-17-36(18-16-34)20-27(37)35(2)24-12-10-23(11-13-24)32-29(21-7-5-4-6-8-21)28-25-14-9-22(31(39)40-3)19-26(25)33-30(28)38/h4-14,19,33,38H,15-18,20H2,1-3H3
  InChIKey: CPMDPSXJELVGJG-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 135423438
  ChEBI ID: CHEBI:85164
  CAS Number: 656247-17-5
  TTD ID: D09HNV
  VARIDT ID: DR00137

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fibroblast growth factor receptor 1 (FGFR1)	TTRLW2X	FGFR1_HUMAN	Modulator	[1]
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Modulator	[1]
Vascular endothelial growth factor receptor (VEGFR)	TTVJ1D8	NOUNIPROTAC	Modulator	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Molecular Expression Atlas of This Drug

• The Studied Disease: Colorectal cancer
• ICD Disease Classification: 2B91.Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Fibroblast growth factor receptor 1 (FGFR1)	DTT	FGFR1	5.16E-02	1.24E-03	4.64E-03
Fms-like tyrosine kinase 3 (FLT-3)	DTT	FLT3	2.64E-120	3.41	4.96
P-glycoprotein 1 (ABCB1)	DTP	P-GP	4.70E-06	-5.80E-02	-1.98E-01

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Accelerated clearance of Intedanib due to the transporter induction by Arn-509.	Acute myeloid leukaemia [2A60]	[48]
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of Intedanib due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[49]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Intedanib due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[50]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Intedanib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[51]
Tucatinib	DMBESUA	Moderate	Decreased clearance of Intedanib due to the transporter inhibition by Tucatinib.	Breast cancer [2C60-2C6Y]	[52]
PF-04449913	DMSB068	Moderate	Decreased clearance of Intedanib due to the transporter inhibition by PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[48]
Lumacaftor	DMCLWDJ	Major	Accelerated clearance of Intedanib due to the transporter induction by Lumacaftor.	Cystic fibrosis [CA25]	[53]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Intedanib and Tazemetostat.	Follicular lymphoma [2A80]	[52]
PF-06463922	DMKM7EW	Major	Increased metabolism of Intedanib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[52]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Intedanib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[52]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Intedanib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[54]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Intedanib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[55]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Intedanib due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[56]
Fedratinib	DM4ZBK6	Moderate	Increased risk of bleeding by the combination of Intedanib and Fedratinib.	Myeloproliferative neoplasm [2A20]	[52]
Rolapitant	DM8XP26	Moderate	Decreased clearance of Intedanib due to the transporter inhibition by Rolapitant.	Nausea/vomiting [MD90]	[57]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Intedanib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[58]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Intedanib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[59]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Intedanib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[48]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Intedanib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[49]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Intedanib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[60]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Intedanib and Betrixaban.	Venous thromboembolism [BD72]	[52]

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