Drug Information

Drug (ID: DG01614) and It's Reported Resistant Information

• Name: G007-LK
• Synonyms: G007-LK; 1380672-07-0; CHEMBL2325503; (E)-4-(5-(2-(4-(2-chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)vinyl)-1,3,4-oxadiazol-2-yl)benzonitrile; 4-[5-[(E)-2-[4-(2-chlorophenyl)-5-(5-methylsulfonylpyridin-2-yl)-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]benzonitrile; 4-{5-[(E)-2-{4-(2-Chlorophenyl)-5-[5-(Methylsulfonyl)pyridin-2-Yl]-4h-1,2,4-Triazol-3-Yl}ethenyl]-1,3,4-Oxadiazol-2-Yl}benzonitrile; benzonitrile, 4-[5-[(1E)-2-[4-(2-chlorophenyl)-5-[5-(methylsulfonyl)-2-pyridinyl]-4H-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]-; 4hyf; C25H16ClN7O3S; SCHEMBL9904844; SCHEMBL9904845; AOB4444; EX-A656; G007 LK;G007LK; G-007-LK; 3686AH; BDBM50427989; s7239; ZINC95582938; CCG-269912; NCGC00390587-01; NCGC00390587-03; AC-33045; AS-75199; B5830; A900891; A1-02247; J-690154; Q27451850; (E)-4-(5-(2-(4-(2-Chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)vinyl)-1,3,4-oxadiazol-2-yl)benzonitrile;G007-LK; 1-[6-(3,5-Dichloro-4-hydroxyphenyl)-4-({trans-4-[(dimethylamino)methyl]cyclohexyl}amino)-1,5-naphthyridin-3-yl]ethanone hydrochlorid e (1:1); 1AK; 4-{5-[(1E)-2-[4-(2-chlorophenyl)-5-(5-methanesulfonylpyridin-2-yl)-4H-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl}benzonitrile
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Colorectal cancer [ICD-11: 2B91]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Colorectal cancer [ICD-11: 2B91]; [1]
• Target: .; NOUNIPROTAC; [1]
• Formula: 6
• IsoSMILES: CS(=O)(=O)C1=CN=C(C=C1)C2=NN=C(N2C3=CC=CC=C3Cl)/C=C/C4=NN=C(O4)C5=CC=C(C=C5)C#N
• InChI: InChI=1S/C25H16ClN7O3S/c1-37(34,35)18-10-11-20(28-15-18)24-31-29-22(33(24)21-5-3-2-4-19(21)26)12-13-23-30-32-25(36-23)17-8-6-16(14-27)7-9-17/h2-13,15H,1H3/b13-12+
• InChIKey: HIWVLHPKZNBSBE-OUKQBFOZSA-N
• PubChem CID: 67960134

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

Colorectal cancer [ICD-11: 2B91]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Adenomatous polyposis coli protein (APC) [1]

• Molecule Alteration: Nonsense; p.L852* (c.2555T>A)
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Adenomatous polyposis coli protein (APC) [1]

• Molecule Alteration: Nonsense; p.Q886* (c.2656C>T)
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data

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

• Molecule Alteration: Missense mutation; p.S33F (c.98C>T)
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DLD1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vivo Model: ApcMin mouse model; Lgr5-GFP-IRES-CreER mouse model; CAGs-rtTA mouse model; Col1A1 mouse model; TG-shApc.2235E mouse model; TG-Ren.713 mouse model; TG-shTnks1/2-3341-1328 mouse model; TG-shTnks1/2-1385-3004 mouse model; Apc Q1405X mouse model; Mus musculus
• Experiment for Molecule Alteration: qPCR

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Adenomatous polyposis coli protein (APC) [2]

• Molecule Alteration: Nonsense; p.W553* (c.1658G>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: SW403 cells; Colon; Homo sapiens (Human); CVCL_0545
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HCC2998 cells; Colon; Homo sapiens (Human); CVCL_1266
• In Vitro Model: COLO-320DM cells; Colon; Homo sapiens (Human); CVCL_0219
• Experiment for Molecule Alteration: Immunofluorescence staining assay; Western blotting analysis
• Experiment for Drug Resistance: MTT assay

Key Molecule: Adenomatous polyposis coli protein (APC) [2]

• Molecule Alteration: Nonsense; p.S811* (c.2432C>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: SW403 cells; Colon; Homo sapiens (Human); CVCL_0545
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HCC2998 cells; Colon; Homo sapiens (Human); CVCL_1266
• In Vitro Model: COLO-320DM cells; Colon; Homo sapiens (Human); CVCL_0219
• Experiment for Molecule Alteration: Immunofluorescence staining assay; Western blotting analysis
• Experiment for Drug Resistance: MTT assay

Key Molecule: Adenomatous polyposis coli protein (APC) [1]

• Molecule Alteration: Nonsense; p.Q1406* (c.4216C>T)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Adenomatous polyposis coli protein (APC) [2]

• Molecule Alteration: Nonsense; p.R216* (c.646C>T)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: SW403 cells; Colon; Homo sapiens (Human); CVCL_0545
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HCC2998 cells; Colon; Homo sapiens (Human); CVCL_1266
• In Vitro Model: COLO-320DM cells; Colon; Homo sapiens (Human); CVCL_0219
• Experiment for Molecule Alteration: Immunofluorescence staining assay; Western blotting analysis
• Experiment for Drug Resistance: MTT assay

References

• Ref 1: Distinct Colorectal Cancer-Associated APC Mutations Dictate Response to Tankyrase InhibitionCancer Discov. 2019 Oct;9(10):1358-1371. doi: 10.1158/2159-8290.CD-19-0289. Epub 2019 Jul 23.
• Ref 2: APC Mutations as a Potential Biomarker for Sensitivity to Tankyrase Inhibitors in Colorectal CancerMol Cancer Ther. 2017 Apr;16(4):752-762. doi: 10.1158/1535-7163.MCT-16-0578. Epub 2017 Feb 8.