Drug Information

Drug (ID: DG00554) and It's Reported Resistant Information

• Name: Erdafitinib
• Synonyms: Erdafitinib; 1346242-81-6; JNJ-42756493; Balversa; UNII-890E37NHMV; 890E37NHMV; JNJ42756493; N'-(3,5-dimethoxyphenyl)-N'-[3-(1-methylpyrazol-4-yl)quinoxalin-6-yl]-N-propan-2-ylethane-1,2-diamine; N1-(3,5-dimethoxyphenyl)-N2-isopropyl-N1-(3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl)ethane-1,2-diamine; Erdafitinib [USAN:INN]; Balversa (TN); Erdafitinib (USAN/INN); GTPL9039; SCHEMBL2583760; CHEMBL3545376; Erdafitinib; JNJ-42756493; JNJ-42756493 (Erdafitinib); AMY31119; BCP20346; EX-A2564; BDBM50525939; MFCD28502040; NSC781556; s8401; compound 4 [WO2011135376]; ZINC168520308; CCG-269200; CS-4988; DB12147; NSC-781556; SB16854; NCGC00475735-01; 1,2-Ethanediamine, N1-(3,5-dimethoxyphenyl)-N2-(1-methylethyl)-N1-(3-(1-methyl-1H-pyrazol-4-yl)-6-quinoxalinyl)-; AC-30222; AS-35040; HY-18708; JNJ 42756493; D10927; A857165; Q27077213; B0084-470835; 5SF; N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine; N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine;Erdafitinib
• Indication:
  In total 4 Indication(s)
  Bladder cancer [ICD-11: 2C94]; Approved; [1]
  Lymphoma [ICD-11: 2A90- 2A85]; Phase 1/2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
  Ureteral cancer [ICD-11: 2C92]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
  Liver cancer [ICD-11: 2C12]; [1]
• Target: .; NOUNIPROTAC; [1]
• Formula: C25H30N6O2
• IsoSMILES: CC(C)NCCN(C1=CC2=NC(=CN=C2C=C1)C3=CN(N=C3)C)C4=CC(=CC(=C4)OC)OC
• 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
• PubChem CID: 67462786
• TTD Drug ID: D0EE8V
• INTEDE ID: DR0595
• DrugBank ID: DB12147

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [2]

• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [2]

• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Liver cancer [ICD-11: 2C12]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [1]

• Molecule Alteration: Missense mutation; p.V550L
• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.

Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [1]

• Molecule Alteration: Missense mutation; p.V550E
• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.

Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [1]

• Molecule Alteration: Missense mutation; p.V550L
• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.

Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [1]

• Molecule Alteration: Missense mutation; p.V550E
• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [1]

• Molecule Alteration: Missense mutation; p.V550M
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.

Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [1]

• Molecule Alteration: Missense mutation; p.V550M
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.

Bladder cancer [ICD-11: 2C94]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [4]

• Molecule Alteration: Missense mutation; p.S371C (c.1111A>T)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [4]

• Molecule Alteration: Missense mutation; p.G380R (c.1138G>A)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [4]

• Molecule Alteration: Synonymous; p.K650K (c.1950G>A)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Transitional cell carcinoma [ICD-11: 2C9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [3]

• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Experimental Note: Identified from the Human Clinical Data

References

• Ref 1: Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance .Br J Cancer. 2021 Mar;124(5):880-892. doi: 10.1038/s41416-020-01157-0. Epub 2020 Dec 3. 10.1038/s41416-020-01157-0
• Ref 2: Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical useOncotarget. 2016 Apr 26;7(17):24252-68. doi: 10.18632/oncotarget.8132.
• Ref 3: Erdafitinib in Locally Advanced or Metastatic Urothelial CarcinomaN Engl J Med. 2019 Jul 25;381(4):338-348. doi: 10.1056/NEJMoa1817323.
• Ref 4: Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivoBr J Cancer. 2011 Jan 4;104(1):75-82. doi: 10.1038/sj.bjc.6606016. Epub 2010 Nov 30.