Details of the Drug

General Information of Drug (ID: DMI782S)

• Drug Name: Erdafitinib
• Synonyms: 1346242-81-6; UNII-890E37NHMV; 890E37NHMV; Erdafitinib [USAN:INN]; Erdafitinib (USAN/INN); GTPL9039; SCHEMBL2583760; CHEMBL3545376; MolPort-044-560-398; JNJ-42756493 (Erdafitinib); s8401; compound 4 [WO2011135376]; ZINC168520308; AKOS030526429; CS-4988; DB12147; AC-30222; 1,2-Ethanediamine, N1-(3,5-dimethoxyphenyl)-N2-(1-methylethyl)-N1-(3-(1-methyl-1H-pyrazol-4-yl)-6-quinoxalinyl)-; HY-18708; AS-35040; KB-333716; D10927; N'-(3,5-dimethoxyphenyl)-N'-[3-(1-methylpyrazol-4-yl)quino

Indication

Disease Entry	ICD 11	Status	REF
Bladder cancer	2C94	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Urothelial carcinoma	2C92.0	Phase 2	[3]
Lymphoma	2A80-2A86	Phase 1/2	[4]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 446.5
  Logarithm of the Partition Coefficient (xlogp); 3.2
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 29,268 mcgh/L []
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1,399 mcg/L []
  Clearance: The apparent oral clearance of drug is 0.362 L/h [5]
  Elimination: About 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged) []
  Half-life: The concentration or amount of drug in body reduced by one-half in 59 hours [5]
  Metabolism: The drug is metabolized via the cytochrome P450 enzym CYP2C9 and CYP3A4 isoenzymes []
  Vd: The volume of distribution (Vd) of drug is 26-29 L [5]
• Chemical Identifiers:
  Formula: C25H30N6O2
  IUPAC Name: N'-(3,5-dimethoxyphenyl)-N'-[3-(1-methylpyrazol-4-yl)quinoxalin-6-yl]-N-propan-2-ylethane-1,2-diamine
  Canonical SMILES: CC(C)NCCN(C1=CC2=NC(=CN=C2C=C1)C3=CN(N=C3)C)C4=CC(=CC(=C4)OC)OC
  InChI: InChI=1S/C25H30N6O2/c1-17(2)26-8-9-31(20-10-21(32-4)13-22(11-20)33-5)19-6-7-23-24(12-19)29-25(15-27-23)18-14-28-30(3)16-18/h6-7,10-17,26H,8-9H2,1-5H3
  InChIKey: OLAHOMJCDNXHFI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 67462786
  CAS Number: 1346242-81-6
  DrugBank ID: DB12147
  TTD ID: D0NW0T
  INTEDE ID: DR0595
• 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	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Regulation of Drug Effects	[7]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Erdafitinib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[8]
Oliceridine	DM6MDCF	Moderate	Increased metabolism of Erdafitinib caused by Oliceridine mediated induction of CYP450 enzyme.	Acute pain [MG31]	[8]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Erdafitinib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[8]
Eslicarbazepine	DMZREFQ	Major	Increased plasma concentrations of Erdafitinib and Eslicarbazepine due to competitive inhibition of the same metabolic pathway.	Epilepsy/seizure [8A61-8A6Z]	[8]
Bay 80-6946	DMLOS5R	Moderate	Increased metabolism of Erdafitinib caused by Bay 80-6946 mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[8]
Rucaparib	DM9PVX8	Moderate	Decreased clearance of Erdafitinib due to the transporter inhibition by Rucaparib.	Ovarian cancer [2C73]	[8]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of Erdafitinib due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[8]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] ClinicalTrials.gov (NCT03210714) Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial). U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036975)
• [5] Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31.
• [6] FDA label of Erdafitinib. The 2020 official website of the U.S. Food and Drug Administration.
• [7] Mechanism-Based Inactivation of Cytochrome P450 3A4 and 3A5 by the Fibroblast Growth Factor Receptor Inhibitor Erdafitinib. Chem Res Toxicol. 2021 Jul 19;34(7):1800-1813. doi: 10.1021/acs.chemrestox.1c00178. Epub 2021 Jun 30.
• [8] Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.