Details of the Drug

General Information of Drug (ID: DMNKBEC)

• Drug Name: Infigratinib
• Synonyms: BGJ398

Indication

Disease Entry	ICD 11	Status	REF
Cholangiocarcinoma	2C12.10	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]

• Affected Organisms: Humans and other mammals
• ATC Code:
  L01EN03: Infigratinib
  L01EN: Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors
  L01E: PROTEIN KINASE INHIBITORS
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 560.5
  Logarithm of the Partition Coefficient (xlogp); 4.7
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 3780 mcgh/L [3]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 282.5 mcg/L [3]
  Clearance: The clearance of drug is 33.1 L/h [3]
  Elimination: Following administration of a single oral dose of radiolabeled infigratinib in healthy subjects, approximately 77% of the dose was recovered in feces, where 3.4% of the dose was in the unchanged parent form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 33.5 hours [3]
  Metabolism: The drug is metabolized via the CYP3A4 and flavin-containing monooxygenase 3 (FMO3) [3]
  Vd: The volume of distribution (Vd) of drug is 1600 L [3]
• Chemical Identifiers:
  Formula: C26H31Cl2N7O3
  IUPAC Name: 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]-1-methylurea
  Canonical SMILES: CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl
  InChI: InChI=1S/C26H31Cl2N7O3/c1-5-34-10-12-35(13-11-34)18-8-6-17(7-9-18)31-21-15-22(30-16-29-21)33(2)26(36)32-25-23(27)19(37-3)14-20(38-4)24(25)28/h6-9,14-16H,5,10-13H2,1-4H3,(H,32,36)(H,29,30,31)
  InChIKey: QADPYRIHXKWUSV-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 53235510
  ChEBI ID: CHEBI:63451
  CAS Number: 872511-34-7
  UNII: A4055ME1VK
  DrugBank ID: DB11886
  TTD ID: D03LWG
• 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
Fibroblast growth factor receptor (FGFR)	TT0LF7H	NOUNIPROTAC	Inhibitor	[4]
Fibroblast growth factor receptor 1 (FGFR1)	TTRLW2X	FGFR1_HUMAN	Modulator	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Fibroblast growth factor receptor 3 (FGFR3)	OTSAXDIL	FGFR3_HUMAN	Drug Response	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Cholangiocarcinoma
• ICD Disease Classification: 2C12.10

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Fibroblast growth factor receptor 1 (FGFR1)	DTT	FGFR1	4.79E-02	-0.03	-0.15

References

• [1] FDA Approved Drug Products from FDA Official Website. 2021. Application Number: 214622.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7877).
• [3] FDA Approved Drug Products: TRUSELTIQ (infigratinib) capsules, for oral use
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
• [6] Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J Med Chem. 2011 Oct 27;54(20):7066-83. doi: 10.1021/jm2006222. Epub 2011 Sep 21.