Drug Information

Drug (ID: DG01582) and It's Reported Resistant Information

• Name: WNT-974
• Synonyms: 1243244-14-5; LGK974; LGK-974; 2-(2',3-Dimethyl-[2,4'-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide; WNT-974; WNT974; LGK 974; UNII-U27F40013Q; CHEBI:78030; LGK974 (WNT974); CHEMBL3188386; 2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]-N-(5-pyrazin-2-ylpyridin-2-yl)acetamide; U27F40013Q; 2-[5-Methyl-6-(2-methyl-4-pyridyl)-3-pyridyl]-N-(5-pyrazin-2-yl-2-pyridyl)acetamide; [2,4'-Bipyridine]-5-acetamide, 2',3-dimethyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-; 2-(2',3-Dimethyl-(2,4'-bipyridin)-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide; 2-(2',3-dimethyl-2,4'-bipyridin-5-yl)-N-[5-(pyrazin-2-yl)pyridin-2-yl]acetamide; NVP-LGK974; MLS006011002; SCHEMBL1723611; GTPL11167; HMS3653G11; BCP08495; EX-A1402; LGK-974 (WNT974); 2140AH; BBL102809; BDBM50133870; CS3177; NSC777639; s7143; STL556617; ZINC95930187; AKOS025211913; CCG-264701; DB12561; NSC-777639; SB19314; NCGC00347950-01; NCGC00347950-02; NCGC00347950-07; NCGC00347950-11; AC-30231; HY-17545; MS-20504; QC-11701; SMR004702800; SW211728-2; J3.551.731F; A890524; AU-004/43508401; J-005066; Q27147596; LGK 974;LGK974; WNT974; WNT 974; WNT-974; 2',3-Dimethyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-[2,4'-bipyridine]-5-acetamide; 2-(2',3-diMethyl-[2,4'-bipyridin]-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetaMide;LGK974
• Indication:
  In total 3 Indication(s)
  Malignant mesothelioma [ICD-11: 2C26]; Phase 1; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
• Target: Mammalian target of rapamycin complex 1 (mTORC1); MTOR_HUMAN-RPTOR_HUMAN-LST8_HUMAN-AKTS1_HUMAN-DPTOR_HUMAN; [1]
• Target: PI3-kinase gamma (PIK3CG); PK3CG_HUMAN; [1]
• Target: Serine/threonine-protein kinase mTOR (mTOR); MTOR_HUMAN; [1]
• Target: Target of rapamycin complex 2 MAPKAP1 (MTORC2); SIN1_HUMAN; [1]
• Formula: 5
• IsoSMILES: CC1=CC(=CN=C1C2=CC(=NC=C2)C)CC(=O)NC3=NC=C(C=C3)C4=NC=CN=C4
• InChI: InChI=1S/C23H20N6O/c1-15-9-17(12-28-23(15)18-5-6-25-16(2)10-18)11-22(30)29-21-4-3-19(13-27-21)20-14-24-7-8-26-20/h3-10,12-14H,11H2,1-2H3,(H,27,29,30)
• InChIKey: XXYGTCZJJLTAGH-UHFFFAOYSA-N
• PubChem CID: 46926973
• ChEBI ID: CHEBI:78030
• TTD Drug ID: D0U3DP
• DrugBank ID: DB12561

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

Head and neck cancer [ICD-11: 2D42]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [1]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.C478F (c.1433G>T)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: HN30 cells; Nasopharyngeal; Homo sapiens (Human); CVCL_5525
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: UMSCC cells; Oral cavity; Homo sapiens (Human); CVCL_7707
• In Vitro Model: Hs840T cells; Pharynx; Homo sapiens (Human); CVCL_0942
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vitro Model: A-253 cells; Salivary gland; Homo sapiens (Human); CVCL_1060
• In Vitro Model: SCC-4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: Hs840.T cells; N.A.; N.A.; N.A.
• In Vivo Model: Nude mouse(or nude rat) xenograft model; Mus musculus
• Experiment for Molecule Alteration: TaqMan assay
• Experiment for Drug Resistance: Colony formation assay

References

• Ref 1: Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20224-9. doi: 10.1073/pnas.1314239110. Epub 2013 Nov 25.