Drug Information

Drug (ID: DG01583) and It's Reported Resistant Information

• Name: MK2206
• Synonyms: 1032350-13-2; MK-2206 dihydrochloride; MK-2206 2HCl; MK2206; UNII-Q34I3E28IO; 8-(4-(1-Aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one dihydrochloride; MK-2206 HCl salt; 8-[4-(1-AMINOCYCLOBUTYL)PHENYL]-9-PHENYL-1,2,4-TRIAZOLO[3,4-F][1,6]NAPHTHYRIDIN-3(2H)-ONE DIHYDROCHLORIDE; Q34I3E28IO; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one;dihydrochloride; C25H21N5O; MK 2206 2HCl; 1032349-77-1; MK 2206 dihydrochloride; C25H21N5O.HCl; C25H21N5O.2HCl; CHEMBL4635254; SCHEMBL17100521; EX-A259; SYN1162; AOB87741; MFCD14584463; s1078; AKOS015966903; CCG-264809; PB19401; 1,2,4-Triazolo(3,4-f)(1,6)naphthyridin-3(2H)-one, 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-, hydrochloride (1:2); 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one;dihydrochl; AC-28437; AS-16298; FT-0672430; SW202557-3; X7427; Z1978; P11738; J-000912; J-519356; Q27286944; (2R,4S)-4-[(3-Carboxy-1-oxopropyl)amino]-4-[(p-phenylphenyl)methyl]-2-methylbutanoic acid ethyl ester; 4-[[(2S,4R)-5-Ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid calcium salt; 4-{[(2S,4R)-1-(4-Biphenylyl)-5-ethoxy-4-methyl-5-oxo-2-pentanyl]amino}-4-oxobutanoic acid; 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl-1,2,4-triazolo[3,4-f][1,6]naphthyridin-3(2H)-one 2HCl; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H,3H-[1,2,4]triazolo[3,4-f]1,6-naphthyridin-3-one hydrochloride
• Indication:
  In total 2 Indication(s)
  Nasopharyngeal carcinoma [ICD-11: 2B6B]; Phase 2; [1]
  Rectal adenocarcinoma [ICD-11: 2B92]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [1]
• Target: RAC-gamma serine/threonine-protein kinase (AKT3); AKT3_HUMAN; [1]
• Formula: 3
• IsoSMILES: C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C4C(=N3)C=CN5C4=NNC5=O)C6=CC=CC=C6)N.Cl.Cl
• InChI: InChI=1S/C25H21N5O.2ClH/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);2*1H
• InChIKey: HWUHTJIKQZZBRA-UHFFFAOYSA-N
• PubChem CID: 46930998

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [1]

• Molecule Alteration: Missense mutation; p.W80A (c.238_239delTGinsGC)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 3T3-L1 cells; Nasopharynx; Mus musculus (Mouse); CVCL_0123
• Mechanism Description: The missense mutation p.W80A (c.238_239delTGinsGC) in gene AKT1 cause the resistance of MK2206 by aberration of the drug's therapeutic target

Myeloproliferative neoplasm [ICD-11: 2A22]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Thrombopoietin receptor (TPOR) [3]

• Molecule Alteration: Missense mutation; p.W515L (c.1544G>T)
• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEL cells; Blood; Homo sapiens (Human); CVCL_0001
• In Vitro Model: SET2 cells; Peripheral blood; Homo sapiens (Human); CVCL_2187
• In Vivo Model: Balb/c donor mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: Trypan blue staining assay
• Mechanism Description: The missense mutation p.W515L (c.1544G>T) in gene MPL cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [2]

• Molecule Alteration: Missense mutation; p.W80A (c.238_239delTGinsGC)
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: HCC4006 cells; Lung; Homo sapiens (Human); CVCL_1269
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• In Vitro Model: GTL-16 cells; Gastric; Homo sapiens (Human); CVCL_7668
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• In Vitro Model: H1648 cells; Lymph node; Homo sapiens (Human); CVCL_1482
• In Vitro Model: EBC1 cells; Skin; Homo sapiens (Human); CVCL_2891
• Mechanism Description: The missense mutation p.W80A (c.238_239delTGinsGC) in gene AKT1 cause the resistance of MK2206 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PI3-kinase alpha (PIK3CA) [4]

• Molecule Alteration: Missense mutation; p.N345K (c.1035T>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.N345K (c.1035T>G) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [4]

• Molecule Alteration: Missense mutation; p.E542K (c.1624G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.E542K (c.1624G>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [4]

• 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: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [4]

• Molecule Alteration: Missense mutation; p.Q546K (c.1636C>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.Q546K (c.1636C>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [4]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [4]

• Molecule Alteration: Missense mutation; p.H1047L (c.3140A>T)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.H1047L (c.3140A>T) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [4]

• Molecule Alteration: Missense mutation; p.G1049R (c.3145G>C)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.G1049R (c.3145G>C) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Thyroid cancer [ICD-11: 2D10]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatase and tensin homolog (PTEN) [5]

• Molecule Alteration: Nonsense; p.R130* (c.388C>T)
• Sensitive Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: C643 cells; Thyroid gland; Homo sapiens (Human); CVCL_5969
• In Vitro Model: HTH7 cells; Thyroid gland; Homo sapiens (Human); CVCL_6289
• In Vitro Model: Hth74 cells; Thyroid gland; Homo sapiens (Human); CVCL_6288
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The nonsense p.R130* (c.388C>T) in gene PTEN cause the sensitivity of MK2206 by unusual activation of pro-survival pathway.

Key Molecule: GTPase Hras (HRAS) [5]

• Molecule Alteration: Missense mutation; p.G13R (c.37G>C)
• Sensitive Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: C643 cells; Thyroid gland; Homo sapiens (Human); CVCL_5969
• In Vitro Model: HTH7 cells; Thyroid gland; Homo sapiens (Human); CVCL_6289
• In Vitro Model: Hth74 cells; Thyroid gland; Homo sapiens (Human); CVCL_6288
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.G13R (c.37G>C) in gene HRAS cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: GTPase Nras (NRAS) [5]

• Molecule Alteration: Missense mutation; p.Q61R (c.182A>G)
• Sensitive Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: C643 cells; Thyroid gland; Homo sapiens (Human); CVCL_5969
• In Vitro Model: HTH7 cells; Thyroid gland; Homo sapiens (Human); CVCL_6289
• In Vitro Model: Hth74 cells; Thyroid gland; Homo sapiens (Human); CVCL_6288
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.Q61R (c.182A>G) in gene NRAS cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [5]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: C643 cells; Thyroid gland; Homo sapiens (Human); CVCL_5969
• In Vitro Model: HTH7 cells; Thyroid gland; Homo sapiens (Human); CVCL_6289
• In Vitro Model: Hth74 cells; Thyroid gland; Homo sapiens (Human); CVCL_6288
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway

References

• Ref 1: Development of a new model system to dissect isoform specific Akt signalling in adipocytesBiochem J. 2015 Jun 15;468(3):425-34. doi: 10.1042/BJ20150191. Epub 2015 Apr 9.
• Ref 2: A kinase-independent function of AKT promotes cancer cell survivalElife. 2014 Dec 31;3:e03751. doi: 10.7554/eLife.03751.
• Ref 3: AKT is a therapeutic target in myeloproliferative neoplasmsLeukemia. 2013 Sep;27(9):1882-90. doi: 10.1038/leu.2013.167. Epub 2013 Jun 10.
• Ref 4: Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare MutationsCancer Res. 2015 Dec 15;75(24):5341-54. doi: 10.1158/0008-5472.CAN-15-1654. Epub 2015 Dec 1.
• Ref 5: The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathwayJ Clin Endocrinol Metab. 2011 Apr;96(4):E577-85. doi: 10.1210/jc.2010-2644. Epub 2011 Feb 2.