Details of the Drug Combination

General Information of Drug Combination (ID: DCEGDDP)

Drug Combination Name
Osimertinib Sapanisertib
Indication
Disease Entry Status REF
Metastatic Lung Non-Small Cell Carcinoma Phase 1 [1]
Component Drugs Osimertinib   DMRJLAT Sapanisertib   DMYZFNH
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Osimertinib
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [2]
Melanoma 2C30 Phase 3 [3]
Osimertinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [8]
------------------------------------------------------------------------------------
Osimertinib Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [9]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Activity [10]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [11]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [12]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [12]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [10]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [13]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Response To Substance [10]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 DOT(s)
Indication(s) of Sapanisertib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [5]
Sapanisertib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [5]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT02503722) Testing the Combination of MLN0128 (TAK-228) and AZD9291 in Advanced EGFR (Epidermal Growth Factor Receptor) Mutation Positive Non-small Cell Lung Cancer
2 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7719).
4 ClinicalTrials.gov (NCT02049957) Safety and Efficacy Study of Sapanisertib in Combination With Exemestane or Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Metastatic Breast Cancer. U.S. National Institutes of Health.
5 Prevent COVID-19 Severity by Repurposing mTOR Inhibitors. 2 April 2020
6 In vitro inhibition of human UDP-glucuronosyltransferase (UGT) 1A1 by osimertinib, and prediction of in vivo drug-drug interactions. Toxicol Lett. 2021 Sep 15;348:10-17. doi: 10.1016/j.toxlet.2021.05.004. Epub 2021 May 24.
7 Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene. 2019 Jan;38(5):656-670. doi: 10.1038/s41388-018-0482-y. Epub 2018 Aug 31.
8 AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.
9 Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway. J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
10 Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells. Toxicol Appl Pharmacol. 2017 Apr 15;321:18-26. doi: 10.1016/j.taap.2017.02.017. Epub 2017 Feb 22.
11 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
12 Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways. Biochem Pharmacol. 2022 Jan;195:114864. doi: 10.1016/j.bcp.2021.114864. Epub 2021 Nov 30.
13 AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells. J Cell Biochem. 2019 Jan;120(1):756-767. doi: 10.1002/jcb.27434. Epub 2018 Aug 26.