Drug Information

Drug (ID: DG01872) and It's Reported Resistant Information

• Name: DHM25
• Synonyms: DHM25
• Target: .; NOUNIPROTAC; [1]

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

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.K111N (c.333G>C)
• 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
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: T47-D cells; Pleural effusion; Homo sapiens (Human); CVCL_0553
• In Vivo Model: NOD/SCID/gamac null mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

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
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: T47-D cells; Pleural effusion; Homo sapiens (Human); CVCL_0553
• In Vivo Model: NOD/SCID/gamac null mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

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

• 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: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: T47-D cells; Pleural effusion; Homo sapiens (Human); CVCL_0553
• In Vivo Model: NOD/SCID/gamac null mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

Key Molecule: Phosphatase and tensin homolog (PTEN) [1]

• Molecule Alteration: Missense mutation; p.V275* (c.823_824delGTinsTA)
• Sensitive Disease: ER negative breast cancer [ICD-11: 2C60.7]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: T47-D cells; Pleural effusion; Homo sapiens (Human); CVCL_0553
• In Vivo Model: NOD/SCID/gamac null mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

Key Molecule: Phosphatase and tensin homolog (PTEN) [1]

• Molecule Alteration: Missense mutation; p.L108R (c.323T>G)
• 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
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: T47-D cells; Pleural effusion; Homo sapiens (Human); CVCL_0553
• In Vitro Model: Hs578T cells; Breast; Homo sapiens (Human); CVCL_0332
• In Vivo Model: NOD/SCID/gamac null mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

References

• Ref 1: A Novel Covalent mTOR Inhibitor, DHM25, Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer CellsJ Med Chem. 2015 Aug 27;58(16):6559-73. doi: 10.1021/acs.jmedchem.5b00991. Epub 2015 Aug 14.