Drug Information

Drug (ID: DG01889) and It's Reported Resistant Information

• Name: Allosteric AKT inhibitors
• Synonyms: Allosteric AKT inhibitors
• Target: .; NOUNIPROTAC; [1]

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

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

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-beta serine/threonine-protein kinase (AKT2) [2]

• Molecule Alteration: Copy number gain; .
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data

Key Molecule: RAC-beta serine/threonine-protein kinase (AKT2) [2]

• Molecule Alteration: Copy number gain; .
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data

Breast cancer [ICD-11: 2C60]

Drug Sensitivity 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.E17K (c.49G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vivo Model: Female NOD/SCID mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Deactivation of Akt by a small molecule inhibitor ,SC66, targeting pleckstrin homology domain and facilitating Akt ubiquitination. A cancer-relevant Akt1 (e17k) mutant is unstable, making it intrinsically sensitive to functional inhibition by SC66 in cellular contexts in which the PI3K inhibition has little inhibitory effect.

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

• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vivo Model: Female NOD/SCID mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of allosteric AKT inhibitors by aberration of the drug's therapeutic target

References

• Ref 1: Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitinationProc Natl Acad Sci U S A. 2011 Apr 19;108(16):6486-91. doi: 10.1073/pnas.1019062108. Epub 2011 Apr 4.
• Ref 2: STATISTICS/DATA TYPE - iGMDR.