Details of the Drug Combination

General Information of Drug Combination (ID: DCAF92R)

Drug Combination Name
Temsirolimus Perifosine
Indication
Disease Entry Status REF
Brain Tumor, Recurrent Phase 1 [1]
Component Drugs Temsirolimus   DMS104F Perifosine   DMVYRH2
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Temsirolimus
Disease Entry ICD 11 Status REF
Renal cell carcinoma 2C90 Approved [2]
Temsirolimus Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [4]
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Temsirolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
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Temsirolimus Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [6]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [6]
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Indication(s) of Perifosine
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
Perifosine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [7]
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Perifosine Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Response To Substance [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [9]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [8]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [10]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Expression [9]
Linker for activation of T-cells family member 2 (LAT2) OTWJDKIH NTAL_HUMAN Decreases Response To Substance [11]
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⏷ Show the Full List of 7 DOT(s)

References

1 ClinicalTrials.gov (NCT02238496) Perifosine and Torisel (Temsirolimus) for Recurrent/Progressive Malignant Gliomas
2 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: 5892).
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: 7424).
4 Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
5 Association of NR1I2, CYP3A5 and ABCB1 genetic polymorphisms with variability of temsirolimus pharmacokinetics and toxicity in patients with metastatic bladder cancer. Cancer Chemother Pharmacol. 2017 Sep;80(3):653-659.
6 Drug Interactions Flockhart Table
7 Company report (Aezsinc)
8 PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. Toxicol Appl Pharmacol. 2019 Oct 15;381:114729. doi: 10.1016/j.taap.2019.114729. Epub 2019 Aug 22.
9 NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia. Sci Rep. 2020 Jun 25;10(1):10315. doi: 10.1038/s41598-020-66223-2.
10 Arsenic trioxide potentiates the anti-cancer activities of sorafenib against hepatocellular carcinoma by inhibiting Akt activation. Tumour Biol. 2015 Apr;36(4):2323-34. doi: 10.1007/s13277-014-2839-3. Epub 2014 Nov 22.
11 Linker for activation of T-cell family member2 (LAT2) a lipid raft adaptor protein for AKT signaling, is an early mediator of alkylphospholipid anti-leukemic activity. Mol Cell Proteomics. 2012 Dec;11(12):1898-912. doi: 10.1074/mcp.M112.019661. Epub 2012 Sep 22.