Drug Information

Drug (ID: DG00626) and It's Reported Resistant Information

• Name: GDC-0623
• Synonyms: GDC-0623; 1168091-68-6; GDC 0623; RG 7421; GDC0623; UNII-HW67545I4Q; G-868; 5-((2-FLUORO-4-IODOPHENYL)AMINO)-N-(2-HYDROXYETHOXY)IMIDAZO[1,5-A]PYRIDINE-6-CARBOXAMIDE; 5-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide; HW67545I4Q; RG-7420; RG-7421; 5-[(2-FLUORO-4-IODOPHENYL)AMINO]-N-(2-HYDROXYETHOXY)IMIDAZO[1,5-A]PYRIDINE-6-CARBOXAMIDE; Imidazo[1,5-a]pyridine-6-carboxamide, 5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)-; MEK inhibitor 1; GTPL9909; SCHEMBL1615104; CHEMBL3330650; CHEBI:167659; AOB87143; BCP28689; EX-A2060; BDBM50025226; MFCD25976760; NSC778590; NSC800998; RG7421; s7553; ZINC43206499; AKOS027253679; CCG-269293; DB11982; NSC-778590; NSC-800998; SB16957; NCGC00351593-05; AS-55986; DA-33609; G868; HY-15610; FT-0769207; G 868; A858271; Q27280129; 5-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-hydroxyethoxy)-amide; 5-(2-Fluoro-4-iodophenylamino)-imidazo[15-a]pyridine-6-carboxylic acid (2-hydroxyethoxy)-amide; 5-(2-Fluoro-4-iodophenylamino)imidazo[1,5-a]pyridine-6-carboxylic acid N-(2-hydroxyethoxy)amide
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Unclassified pleomorphic sarcoma [ICD-11: 2B54]; [1]
• Target: ERK activator kinase (MEK); NOUNIPROTAC; [1]
• Formula: C16H14FIN4O3
• IsoSMILES: C1=CC(=C(C=C1I)F)NC2=C(C=CC3=CN=CN32)C(=O)NOCCO
• InChI: 1S/C16H14FIN4O3/c17-13-7-10(18)1-4-14(13)20-15-12(16(24)21-25-6-5-23)3-2-11-8-19-9-22(11)15/h1-4,7-9,20,23H,5-6H2,(H,21,24)
• InChIKey: RFWVETIZUQEJEF-UHFFFAOYSA-N
• PubChem CID: 42642654
• TTD Drug ID: D0R3VK
• DrugBank ID: DB11982

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Unclassified pleomorphic sarcoma [ICD-11: 2B54]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase HRas (HRAS) [1]

• Molecule Alteration: Missense mutation; p.G12V
• Resistant Disease: Unclassified pleomorphic sarcoma [ICD-11: 2B54.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: RAS signaling pathway; Activation; hsa04014
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: SCID/Beige mice model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western blotting assay
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Hras G12V mutation changed the drug target,impairing the ability to inhibit RAS-RAF-MEK-ERK signaling.

References

• Ref 1: Sensitivity and Resistance of Oncogenic RAS-Driven Tumors to Dual MEK and ERK Inhibition .Cancers (Basel). 2021 Apr 13;13(8):1852. doi: 10.3390/cancers13081852. 10.3390/cancers13081852