Drug Information

Drug (ID: DG01545) and It's Reported Resistant Information

• Name: MK-2206
• Synonyms: MK-2206; 1032349-93-1; UNII-51HZG6MP1K; MK 2206; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one; MK2206; 51HZG6MP1K; CHEMBL1079175; CHEBI:67271; NCGC00186465-01; DSSTox_CID_28874; DSSTox_RID_83143; DSSTox_GSID_48948; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one; 1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one, 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-;1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one, 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-;8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-ol; 8-(4-(1-Aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthy ridin-3(2H)-one; 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one; CAS-1032350-13-2; 1032349-77-1; MK-2206 free base; SCHEMBL530721; GTPL7945; DTXSID3048948; BCP20200; Tox21_113368; BDBM50313650; NSC756656; NSC800794; ZINC36382821; AKOS032945686; Tox21_113368_1; BCP9000938; MK 2206;MK2206; NSC-756656; NSC-800794; SB16805; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one; NCGC00186465-02; NCGC00186465-03; NCGC00186465-04; NCGC00186465-08; DB-058959; FT-0738942; A25240; MK2206;MK 2206;MK-2206 dihydrochloride; cas:1032350-13-2;MK 2206; BRD-K68065987-300-02-6; Q25100065; 1,2,4-Triazolo(3,4-f)(1,6)naphthyridin-3(2H)-one, 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-; 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl-1,2,4-triazolo[3,4-f][1,6]naphthyridin-3(2H)-one dihydrochloride;MK-2206 Dihydrochloride; 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-3(2H)-one
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Target: MAPK/ERK kinase kinase (MAP3K); NOUNIPROTAC; [2]
• Formula: 3
• IsoSMILES: C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C4C(=N3)C=CN5C4=NNC5=O)C6=CC=CC=C6)N
• InChI: InChI=1S/C25H21N5O/c26-25(12-4-13-25)18-9-7-17(8-10-18)22-19(16-5-2-1-3-6-16)15-20-21(27-22)11-14-30-23(20)28-29-24(30)31/h1-3,5-11,14-15H,4,12-13,26H2,(H,29,31)
• InChIKey: ULDXWLCXEDXJGE-UHFFFAOYSA-N
• PubChem CID: 24964624
• ChEBI ID: CHEBI:67271
• TTD Drug ID: D0I3RD

Type(s) of Resistant Mechanism of This Drug

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Pancreatic cancer [ICD-11: 2C10]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase KRas (KRAS) [2]

• Molecule Alteration: Missense mutation; p.G12D (c.35G>A)
• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The missense mutation p.G12D (c.35G>A) in gene KRAS cause the sensitivity of MK-2206 by unusual activation of pro-survival pathway

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of MK-2206 by aberration of the drug's therapeutic target

References

• Ref 1: PIK3CA and AKT1 mutations have distinct effects on sensitivity to targeted pathway inhibitors in an isogenic luminal breast cancer model systemClin Cancer Res. 2013 Oct 1;19(19):5413-22. doi: 10.1158/1078-0432.CCR-13-0884. Epub 2013 Jul 25.
• Ref 2: First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumorsJ Clin Oncol. 2011 Dec 10;29(35):4688-95. doi: 10.1200/JCO.2011.35.5263. Epub 2011 Oct 24.