Drug Information

Drug (ID: DG01615) and It's Reported Resistant Information

• Name: Mps-BAY2b
• Synonyms: CHEMBL3410060; N-cyclopropyl-4-{8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}benzamide; 1263420-68-3; SCHEMBL9938616; BDBM50072833; N-cyclopropyl-4-[8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-3-yl]benzamide; 8Q5
• Formula: 6
• IsoSMILES: CC(C)CNC1=NC=CN2C1=NC=C2C3=CC=C(C=C3)C(=O)NC4CC4
• InChI: InChI=1S/C20H23N5O/c1-13(2)11-22-18-19-23-12-17(25(19)10-9-21-18)14-3-5-15(6-4-14)20(26)24-16-7-8-16/h3-6,9-10,12-13,16H,7-8,11H2,1-2H3,(H,21,22)(H,24,26)
• InChIKey: QTOFVYOMOKYCEQ-UHFFFAOYSA-N
• PubChem CID: 67974488

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

Colon cancer [ICD-11: 2B90]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Catenin beta-1 (CTNNB1) [1]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: IF-deletion; p.S45delS (c.133_135delTCT)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: TOV-21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: TOV-112D cells; Ovary; Homo sapiens (Human); CVCL_3612
• In Vitro Model: LS 174T cells; Colon; Homo sapiens (Human); CVCL_1384
• In Vitro Model: A427 cells; Lung; Homo sapiens (Human); CVCL_1055
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Gene set analysis
• Experiment for Drug Resistance: Cell proliferation assay
• Mechanism Description: The if-deletion p.S45delS (c.133_135delTCT) in gene CTNNB1 cause the sensitivity of Mps-BAY2b by unusual activation of pro-survival pathway.

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Catenin beta-1 (CTNNB1) [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Missense mutation; p.S45F (c.134C>T)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.20 Å; PDB: 6O9B
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.45 Å; PDB: 6O9C

RMSD: 0.23; TM score: 0.84883; Amino acid change: S45F

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: TOV-21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: TOV-112D cells; Ovary; Homo sapiens (Human); CVCL_3612
• In Vitro Model: LS 174T cells; Colon; Homo sapiens (Human); CVCL_1384
• In Vitro Model: A427 cells; Lung; Homo sapiens (Human); CVCL_1055
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Gene set analysis
• Experiment for Drug Resistance: Cell proliferation assay
• Mechanism Description: The missense mutation p.S45F (c.134C>T) in gene CTNNB1 cause the sensitivity of Mps-BAY2b by unusual activation of pro-survival pathway

Key Molecule: Catenin beta-1 (CTNNB1) [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Missense mutation; p.S33Y (c.98C>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: TOV-21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: TOV-112D cells; Ovary; Homo sapiens (Human); CVCL_3612
• In Vitro Model: LS 174T cells; Colon; Homo sapiens (Human); CVCL_1384
• In Vitro Model: A427 cells; Lung; Homo sapiens (Human); CVCL_1055
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Gene set analysis
• Experiment for Drug Resistance: Cell proliferation assay
• Mechanism Description: The missense mutation p.S33Y (c.98C>A) in gene CTNNB1 cause the sensitivity of Mps-BAY2b by unusual activation of pro-survival pathway

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Catenin beta-1 (CTNNB1) [1]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Missense mutation; p.T41A (c.121A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: TOV-21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: TOV-112D cells; Ovary; Homo sapiens (Human); CVCL_3612
• In Vitro Model: LS 174T cells; Colon; Homo sapiens (Human); CVCL_1384
• In Vitro Model: A427 cells; Lung; Homo sapiens (Human); CVCL_1055
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Gene set analysis
• Experiment for Drug Resistance: Cell proliferation assay
• Mechanism Description: The missense mutation p.T41A (c.121A>G) in gene CTNNB1 cause the sensitivity of Mps-BAY2b by unusual activation of pro-survival pathway

References

• Ref 1: TTK Inhibitors as a Targeted Therapy for CTNNB1 (Beta-catenin) Mutant CancersMol Cancer Ther. 2017 Nov;16(11):2609-2617. doi: 10.1158/1535-7163.MCT-17-0342. Epub 2017 Jul 27.