Drug Information

Drug (ID: DG00547) and It's Reported Resistant Information

• Name: Dovitinib
• Synonyms: Dovitinib; 405169-16-6; CHIR-258; TKI-258; 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one; Chir 258; Dovitinib (TKI-258, CHIR-258); CHIR258; TKI258; UNII-I35H55G906; Dovitinib lactate; CHEMBL522892; 804551-71-1; CHEMBL4578973; MFCD10565680; I35H55G906; TKI 258; 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one; 4-Amino-5-Fluoro-3-(6-(4-Methylpiperazin-1-yl)-1H-Benzo[D]Imidazol-2-yl)Quinolin-2(1H)-One; (3Z)-4-Amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydro-2H-benzimidazol-2-ylidene]-2(3H)-quinolinone; (3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1,3-dihydrobenzimidazol-2-ylidene]quinolin-2-one; 1027263-12-2; C21H21FN6O; Dovitinib [INN]; 4-AMINO-5-FLUORO-3-[ 5- (4-METHYLPIPERAZIN-1-YL)-1H-BENZIMIDAZOL-2-YL]QUINOLIN-2(1H)-ONE; 38O; TK-258; Kinome_1513; Dovitinib (TKI-258); NVP-TKI258; MLS006009991; SCHEMBL172687; GFKI-258; GTPL5962; SCHEMBL9975396; SCHEMBL20399550; BDBM25118; CHEBI:91395; AOB6730; QCR-175; SYN1029; BCPP000286; BDBM153731; CHIR-258(Dovitinib,TKI258); Dovitinib,TKI258, CHIR-258; HMS3295E21; HMS3651E03; BCP01981; EX-A2051; ZINC3816310; CHIR-258, TKI258, Dovitinib; CHIR258 (TKI-258); BDBM50507579; NSC759661; NSC800092; NSC807408; s1018; ZINC18710083; Dovitinib; TKI-258; CHIR-258; AKOS005146311; AKOS015951093; ZINC100270141; BCP9000518; CCG-264778; CS-0120; DB05928; NSC-759661; NSC-800092; NSC-807408; PB13248; SB20297; 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1h-benzimidazol-2-yl]-1h-quinolin-2-one; NCGC00249685-01; NCGC00249685-02; NCGC00249685-11; (3E)-4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1,3-dihydrobenzimidazol-2-ylidene]quinolin-2-one; 1447274-99-8; AC-32059; AS-19556; HY-50905; SMR004701066; FT-0667782; SW219787-1; Y0345; EC-000.2257; A24080; C75053; TKI-258;CHIR-258;Unii-I35H55G906; 169A166; 326D834; 1,3-benzodiazol-2-yl]-1,2-dihydroquinolin-2-one; J-514396; BRD-K85402309-001-01-7; Q27077102; Q27163255; Q27453625; 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-; B2693-091881; 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1h-benzimidazol-2-yl]quinolin-2 (1h)-one; 4-amino-5-fluoro-3-[6(4-methyl-1-piperazinyl)-1h-benzimidazol-2-yl]-2(1h)-quinolinone; 4-amino-5-fluoro-3-[6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one; 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazole-2-yl]quinolin-2(1H)-one; (3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril; 4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-quinolinone; 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-1,3-benzodiazol-2-ylidene]-2,3-dihydroquinolin-2-one; 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-1,3-benzodiazol-2-yl]-1,2-dihydroquinolin-2-one
• Indication:
  In total 3 Indication(s)
  Endometrial cancer [ICD-11: 2C76]; Investigative; [1]
  Renal cell carcinoma [ICD-11: 2C90]; Investigative; [1]
  Triple negative breast cancer [ICD-11: 2C60-2C6Y]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Liver cancer [ICD-11: 2C12]; [1]
• Target: Fibroblast growth factor receptor 3 (FGFR3); FGFR3_HUMAN; [1]
• Target: Platelet-derived growth factor receptor (PDGFR); NOUNIPROTAC; [1]
• Formula: C21H21FN6O
• IsoSMILES: CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N
• InChI: 1S/C21H21FN6O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29)
• InChIKey: PIQCTGMSNWUMAF-UHFFFAOYSA-N
• PubChem CID: 135398510
• TTD Drug ID: D07OZR
• DrugBank ID: DB05928

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

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

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 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.M538I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.M536I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.L618M
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.I548V
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.M538I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.M536I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.L618M
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Molecule Alteration: Missense mutation; p.I548V
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Kidney cancer [ICD-11: 2C90]

Drug Sensitive Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-21 [2]

• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Molecule Alteration: Expression; Down-regulation
• Mechanism Description: In vitro, miR-21 was also overexpressed in renal carcinoma cell lines compared to HK-2 human proximal tubule epithelial cell line. Moreover, using Boyden chambers and western blot techniques, we also showed that miR-21 overexpression increased migratory, invasive, proliferative, and anti-apoptotic signaling pathways whereas opposite results were observed using an anti-miR-21-based silencing strategy. Finally, we assessed the role of miR-21 in mediating renal cell carcinoma chemoresistance and further showed that miR-21 silencing significantly (1) increased chemosensitivity of paclitaxel, 5-fluorouracil, oxaliplatin, and dovitinib.

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: APC Mutations as a Potential Biomarker for Sensitivity to Tankyrase Inhibitors in Colorectal CancerMol Cancer Ther. 2017 Apr;16(4):752-762. doi: 10.1158/1535-7163.MCT-16-0578. Epub 2017 Feb 8.