Drug Information

Drug (ID: DG01653) and It's Reported Resistant Information

• Name: BAY1436032
• Synonyms: BAY-1436032; 1803274-65-8; BAY1436032; 3-(2-((4-(trifluoromethoxy)phenyl)amino)-1-((1R,5R)-3,3,5-trimethylcyclohexyl)-1H-benzo[d]imidazol-5-yl)propanoic acid; BAY 1436032; CHEMBL4206033; SCHEMBL17009632; BDBM404661; EX-A1606; NSC794487; s8530; NSC-794487; US10344004, Test compound Table 3; HY-100020; CS-0017982; 3-[2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
• Target: Fibroblast growth factor receptor (FGFR); NOUNIPROTAC; [1]
• Formula: 7
• IsoSMILES: C[C@H]1C[C@H](CC(C1)(C)C)N2C3=C(C=C(C=C3)CCC(=O)O)N=C2NC4=CC=C(C=C4)OC(F)(F)F
• InChI: InChI=1S/C26H30F3N3O3/c1-16-12-19(15-25(2,3)14-16)32-22-10-4-17(5-11-23(33)34)13-21(22)31-24(32)30-18-6-8-20(9-7-18)35-26(27,28)29/h4,6-10,13,16,19H,5,11-12,14-15H2,1-3H3,(H,30,31)(H,33,34)/t16-,19+/m0/s1
• InChIKey: RNMAUIMMNAHKQR-QFBILLFUSA-N
• PubChem CID: 118310260
• TTD Drug ID: D0H9FR

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

Acute myeloid leukemia [ICD-11: 2A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Molecule Alteration: Missense mutation; p.R132S (c.394C>A)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HoxA9-IDH2R140Q cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH2172K cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132H cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132C cells; N.A.; .; N.A.
• In Vivo Model: mouse PDX model; Mus musculus
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: BAY1436032 inhibits proliferation and induces differentiation in primary human AML cells. BAY1436032 clears AML blasts in vivo and prolongs survival in PDX models of IDH1 mutant AML. BAY1436032 induces myeloid differentiation in IDH1 mutant AML PDX models in vivo and depletes leukemic stem cells by induction of myeloid differentiation and inhibition of cell cycle progression.

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Molecule Alteration: Missense mutation; p.R132G (c.394C>G)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HoxA9-IDH2R140Q cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH2172K cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132H cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132C cells; N.A.; .; N.A.
• In Vivo Model: mouse PDX model; Mus musculus
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: BAY1436032 inhibits proliferation and induces differentiation in primary human AML cells. BAY1436032 clears AML blasts in vivo and prolongs survival in PDX models of IDH1 mutant AML. BAY1436032 induces myeloid differentiation in IDH1 mutant AML PDX models in vivo and depletes leukemic stem cells by induction of myeloid differentiation and inhibition of cell cycle progression.

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Molecule Alteration: Missense mutation; p.R132C (c.394C>T)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HoxA9-IDH2R140Q cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH2172K cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132H cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132C cells; N.A.; .; N.A.
• In Vivo Model: mouse PDX model; Mus musculus
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: BAY1436032 inhibits proliferation and induces differentiation in primary human AML cells. BAY1436032 clears AML blasts in vivo and prolongs survival in PDX models of IDH1 mutant AML. BAY1436032 induces myeloid differentiation in IDH1 mutant AML PDX models in vivo and depletes leukemic stem cells by induction of myeloid differentiation and inhibition of cell cycle progression.

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HoxA9-IDH2R140Q cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH2172K cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132H cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132C cells; N.A.; .; N.A.
• In Vivo Model: mouse PDX model; Mus musculus
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: BAY1436032 inhibits proliferation and induces differentiation in primary human AML cells. BAY1436032 clears AML blasts in vivo and prolongs survival in PDX models of IDH1 mutant AML. BAY1436032 induces myeloid differentiation in IDH1 mutant AML PDX models in vivo and depletes leukemic stem cells by induction of myeloid differentiation and inhibition of cell cycle progression.

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Molecule Alteration: Missense mutation; p.R132L (c.395G>T)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HoxA9-IDH2R140Q cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH2172K cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132H cells; N.A.; .; N.A.
• In Vitro Model: HoxA9-IDH1R132C cells; N.A.; .; N.A.
• In Vivo Model: mouse PDX model; Mus musculus
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: BAY1436032 inhibits proliferation and induces differentiation in primary human AML cells. BAY1436032 clears AML blasts in vivo and prolongs survival in PDX models of IDH1 mutant AML. BAY1436032 induces myeloid differentiation in IDH1 mutant AML PDX models in vivo and depletes leukemic stem cells by induction of myeloid differentiation and inhibition of cell cycle progression.

References

• Ref 1: Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivoLeukemia. 2017 Oct;31(10):2020-2028. doi: 10.1038/leu.2017.46. Epub 2017 Jan 31.