Drug Information

Drug (ID: DG01616) and It's Reported Resistant Information

• Name: MTOR inhibitors
• Synonyms: UNII-843G0TDV51; ME-344; 843G0TDV51; 1374524-68-1; 4,4'-(7-Hydroxy-8-methylchroman-3,4-diyl)diphenol; GTPL7961; SCHEMBL10073998; DB13062; 2H-1-Benzopyran-7-ol, 3,4-dihydro-3,4-bis(4-hydroxyphenyl)-8-methyl-, (3R,4S)-; Q27083823; 4,4'-((3R,4S)-7-Hydroxy-8-methylchroman-3,4-diyl)diphenol; (3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol
• Indication:
  In total 3 Indication(s)
  Lymphangioleiomyomatosis [ICD-11: CB07]; Phase 1/2; [1]
  Middle East Respiratory Syndrome (MERS) [ICD-11: 1D64]; Investigative; [1]
  Severe acute respiratory syndrome (SARS) [ICD-11: 1D65]; Investigative; [1]
• Target: HUMAN mammalian target of rapamycin (mTOR); MTOR_HUMAN; [1]
• Formula: 2
• IsoSMILES: CC1=C(C=CC2=C1OC[C@H]([C@H]2C3=CC=C(C=C3)O)C4=CC=C(C=C4)O)O
• InChI: InChI=1S/C22H20O4/c1-13-20(25)11-10-18-21(15-4-8-17(24)9-5-15)19(12-26-22(13)18)14-2-6-16(23)7-3-14/h2-11,19,21,23-25H,12H2,1H3/t19-,21-/m0/s1
• InChIKey: QVCAATSEPLQVBX-FPOVZHCZSA-N
• PubChem CID: 68026984

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

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ephrin type-A receptor 2 (EPHA2) [1]

• Molecule Alteration: Missense mutation; p.G391R (c.1171G>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H226 Cells; Lung; Homo sapiens (Human); CVCL_1544
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: H2170 cells; Lung; Homo sapiens (Human); CVCL_1535
• In Vitro Model: H1838 cells; Lung; Homo sapiens (Human); CVCL_1499
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SKLU-1 cells; Lung; Homo sapiens (Human); CVCL_0629
• In Vitro Model: H661 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H522 cells; Lung; Homo sapiens (Human); CVCL_1567
• In Vitro Model: H358 cells; Lung; Homo sapiens (Human); CVCL_1559
• In Vitro Model: H1993 cells; Lymph node; Homo sapiens (Human); CVCL_1512
• In Vitro Model: H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.G391R (c.1171G>A) in gene EPHA2 cause the sensitivity of MTOR inhibitors by unusual activation of pro-survival pathway

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatase and tensin homolog (PTEN) [2]

• Molecule Alteration: Nonsense; p.R233* (c.697C>T)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The nonsense p.R233* (c.697C>T) in gene PTEN cause the sensitivity of MTOR inhibitors by unusual activation of pro-survival pathway.

Endometrial cancer [ICD-11: 2C76]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PI3-kinase regulatory subunit beta (PIK3R2) [3]

• Molecule Alteration: Missense mutation; p.N561D (c.1681A>G)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole-gene resequencing assay
• Mechanism Description: The missense mutation p.N561D (c.1681A>G) in gene PIK3R2 cause the sensitivity of MTOR inhibitors by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase regulatory subunit beta (PIK3R2) [3]

• Molecule Alteration: Missense mutation; p.A171V (c.512C>T)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Identified from the Human Clinical Data

References

• Ref 1: EphA2 mutation in lung squamous cell carcinoma promotes increased cell survival, cell invasion, focal adhesions, and mammalian target of rapamycin activationJ Biol Chem. 2010 Jun 11;285(24):18575-85. doi: 10.1074/jbc.M109.075085. Epub 2010 Apr 1.
• Ref 2: The PI3K pathway as drug target in human cancerJ Clin Oncol. 2010 Feb 20;28(6):1075-83. doi: 10.1200/JCO.2009.25.3641. Epub 2010 Jan 19.
• Ref 3: High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stabilityCancer Discov. 2011 Jul;1(2):170-85. doi: 10.1158/2159-8290.CD-11-0039. Epub 2011 Jun 7.