Drug Information

Drug (ID: DG01588) and It's Reported Resistant Information

• Name: BMS-911543
• Synonyms: BMS-911543; 1271022-90-2; BMS911543; BMS 911543; UNII-7N03P021J8; N,N-dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide; 7N03P021J8; N,N-Dicyclopropyl-4-[(1,5-Dimethyl-1h-Pyrazol-3-Yl)amino]-6-Ethyl-1-Methyl-1,6-Dihydroimidazo[4,5-D]pyrrolo[2,3-B]pyridine-7-Carboxamide; N,N-dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo(4,5-d)pyrrolo(2,3b)pyridine-7-carboxamide; GTPL7954; SCHEMBL1512419; CHEMBL3545215; DTXSID00155403; HMS3747C07; AOB87390; BCP07258; EX-A1551; WAC02290; BDBM50122318; MFCD22200575; NSC766821; NSC799366; s7144; AKOS027251175; JAK2 INHIBITOR BMS-911543; ZINC100468481; CCG-269045; CS-3237; DB12591; NSC-766821; NSC-799366; SB16625; NCGC00345798-01; NCGC00345798-06; AC-29054; AS-17031; HY-15270; Imidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide, N,N-dicyclopropyl-4-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-6-ethyl-1,6-dihydro-1-methyl-; QC-11446; FT-0697510; A908362; Q27075379; 50V; N,N-dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo(4,5-d); N,N-dicyclopropyl-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide; N,N-dicyclopropyl-7-[(1,5-dimethylpyrazol-3-yl)amino]-10-ethyl-3-methyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaene-11-carboxamide
• Indication:
  In total 3 Indication(s)
  Melanoma [ICD-11: 2C30]; Phase 2; [1]
  Melanoma [ICD-11: 2C30]; Phase 2; [1]
  Melanoma [ICD-11: 2C30]; Phase 2; [1]
• Target: Serine/threonine-protein kinase B-raf (BRAF); BRAF_HUMAN; [1]
• Formula: 6
• IsoSMILES: CCN1C(=CC2=C3C(=C(N=C21)NC4=NN(C(=C4)C)C)N=CN3C)C(=O)N(C5CC5)C6CC6
• InChI: InChI=1S/C23H28N8O/c1-5-30-17(23(32)31(14-6-7-14)15-8-9-15)11-16-20-19(24-12-28(20)3)21(26-22(16)30)25-18-10-13(2)29(4)27-18/h10-12,14-15H,5-9H2,1-4H3,(H,25,26,27)
• InChIKey: JCINBYQJBYJGDM-UHFFFAOYSA-N
• PubChem CID: 50922691
• TTD Drug ID: D0TK7R
• INTEDE ID: DR00775
• DrugBank ID: DB12591

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Myeloproliferative neoplasm [ICD-11: 2A22]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [1]

• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: [3H] thymidine incorporation assay
• Mechanism Description: The missense mutation p.V617F (c.1849G>T) in gene JAK2 cause the sensitivity of BMS-911543 by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Thrombopoietin receptor (TPOR) [1]

• Molecule Alteration: Missense mutation; p.W515L (c.1544G>T)
• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: [3H] thymidine incorporation assay
• Mechanism Description: The missense mutation p.W515L (c.1544G>T) in gene MPL cause the sensitivity of BMS-911543 by unusual activation of pro-survival pathway

Hematologic cancer [ICD-11: 2B3Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [1]

• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: [3H] thymidine incorporation assay
• Mechanism Description: The missense mutation p.V617F (c.1849G>T) in gene JAK2 cause the sensitivity of BMS-911543 by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Thrombopoietin receptor (TPOR) [1]

• Molecule Alteration: Missense mutation; p.W515L (c.1544G>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: [3H] thymidine incorporation assay
• Mechanism Description: The missense mutation p.W515L (c.1544G>T) in gene MPL cause the sensitivity of BMS-911543 by unusual activation of pro-survival pathway

ICD-03: Blood/blood-forming organs diseases

Essential thrombocythemia [ICD-11: 3B63]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [1]

• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Disease: Essential thrombocythemia [ICD-11: 3B63.Z]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: [3H] thymidine incorporation assay
• Mechanism Description: The missense mutation p.V617F (c.1849G>T) in gene JAK2 cause the sensitivity of BMS-911543 by aberration of the drug's therapeutic target

References

• Ref 1: Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2Leukemia. 2012 Feb;26(2):280-8. doi: 10.1038/leu.2011.292. Epub 2011 Oct 21.