Drug Information

Drug (ID: DG00357) and It's Reported Resistant Information

• Name: Braf inhibitor
• Synonyms: BRAF inhibitor; N-[2,4-Difluoro-3-[[5-(3-pyridinyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]phenyl]-2-propanesulfonamide; C22H18F2N4O2S; N-(2,4-Difluoro-3-{[5-(3-pyridinyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl}phenyl)-2-propanesulfonamide; SCHEMBL150401; BCP27823; EX-A2629; 5506AC; ZINC71257194; AKOS025117572; CS-0055; PLX-4032(RG7204); NCGC00378825-01; AC-25237; HY-10247; DB-003735; R7204; F12499; 505D610; 2-Propanesulfonamide, N-[2,4-difluoro-3-[[5-(3-pyridinyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]phenyl]-; N-(2,4-difluoro-3-(5-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)phenyl)propane-2-sulfonamide; propane-2-sulfonic acid [2,4-difluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-carbonyl)-phenyl]-amide; propane-2-sulfonic acid [2,4-difluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Melanoma [ICD-11: 2C30]; [1]
• Formula: C22H18F2N4O3S
• IsoSMILES: CC(C)S(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)C4=CN=CC=C4)F
• InChI: 1S/C22H18F2N4O3S/c1-12(2)32(30,31)28-18-6-5-17(23)19(20(18)24)21(29)16-11-27-22-15(16)8-14(10-26-22)13-4-3-7-25-9-13/h3-12,28H,1-2H3,(H,26,27)
• InChIKey: SUNCACOTKLUNHD-UHFFFAOYSA-N
• PubChem CID: 53438230

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

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Nras (NRAS) [1]

• Molecule Alteration: Mutation; .
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT signaling pathway; Activation; hsa04151
• Experiment for Molecule Alteration: Next-generation sequencing assay
• Mechanism Description: Data suggest that the presence of mutated NRAS in the melanoma cell population in parallel with mutated BRAF cells results in resistance to BRAF inhibitors, most probably selecting NRAS-mutated cells in the advancing tumor.

Key Molecule: Homeobox protein Hox-D8 (HOXD8) [1]

• Molecule Alteration: Mutation; .
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT signaling pathway; Activation; hsa04151
• Experiment for Molecule Alteration: Next-generation sequencing assay
• Mechanism Description: Earlier, it was demonstrated that RAC1codon29 mutant melanomas are resistant to this therapy. Later, it was found that a rare genetic alteration, the mutation of HOXD8, can also be the cause of primary resistance to BRAF inhibitors.

References

• Ref 1: Genetic progression of malignant melanoma. Cancer Metastasis Rev. 2016 Mar;35(1):93-107. doi: 10.1007/s10555-016-9613-5.