Drug Information

Drug (ID: DG01584) and It's Reported Resistant Information

• Name: LY-2874455
• Synonyms: LY2874455; 1254473-64-7; LY-2874455; UNII-E9M363811V; LY 2874455; CHEMBL3828009; E9M363811V; (R,E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol; C21H19Cl2N5O2; (R,E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol.; 2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol; (R,E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)-ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol; LY2874455 monohydrate; SCHEMBL298445; SCHEMBL298446; GTPL8104; QCR-90; DTXSID20154776; BCP04756; EX-A1340; 2529AH; BDBM50189781; NSC771750; NSC783670; s7057; ZINC73069242; AKOS027251051; BCP9000878; CCG-269169; CS-0907; DB13022; LM 1476; NSC-771750; NSC-783670; (R,E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethan-1-ol; AC-33003; AS-74798; HY-13304; BCP0726000015; C72002; LY2874455/LY-2874455; J-690104; Q27082753; (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol; 2-{4-[(1E)-2-{5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl}ethenyl]-1H-pyrazol-1-yl}ethan-1-ol
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [1]
• Target: Fibroblast growth factor receptor 2 (FGFR2); FGFR2_HUMAN; [1]
• Formula: 7
• IsoSMILES: C[C@H](C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3/C=C/C4=CN(N=C4)CCO
• InChI: InChI=1S/C21H19Cl2N5O2/c1-13(21-17(22)10-24-11-18(21)23)30-15-3-5-20-16(8-15)19(26-27-20)4-2-14-9-25-28(12-14)6-7-29/h2-5,8-13,29H,6-7H2,1H3,(H,26,27)/b4-2+/t13-/m1/s1
• InChIKey: GKJCVYLDJWTWQU-CXLRFSCWSA-N
• PubChem CID: 46944259
• DrugBank ID: DB13022

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 Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]

• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; N.A.
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of LY-2874455 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]

• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; N.A.
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]

• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; N.A.
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]

• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; N.A.
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

References

• Ref 1: Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive CholangiocarcinomaCancer Discov. 2017 Mar;7(3):252-263. doi: 10.1158/2159-8290.CD-16-1000. Epub 2016 Dec 29.