II. Indications
- Solid Organ Transplant Immunosuppression (maintenance prevention of rejection)
- Tuburous Sclerosis
- Cancer
- Ongoing research into mTOR Inhibitors as anti-aging drugs
- Resources
- Rapamycin (Peter Attia, Drive)
- References
- Resources
III. Mechanism
-
Mammalian Target of Rapamycin Pathway (mTOR Pathway)
- Mammalian Target of RapamycinProtein (mTOR Protein)
- mTOR has multiple associated triggers in pathophysiology
- Cancer formation and Angiogenesis
- Insulin Resistance and Diabetes Mellitus
- Adipogenesis
- T-Lymphocyte activation
- mTOR Inhibitors
- Rapamycin (a Macrolide), and its analogs bind and inhibit mTOR
- Block the Serine-Threonine kinase receptor signaling
- Inhibit mRNA expression related to Cell Cycle progression and arrest cell in G1 phase
IV. Medications
V. Adverse Effects
- Nephrotoxicity including Proteinuria
- Myelosuppression
- Rash
- Delayed Wound Healing
- Secondary Malignancy (including Lymphoma)
- Male Infertility
- Cardiopulmonary
- Interstitial Lung Disease or Pulmonary fibrosis
- Hyperlipidemia
- Edema
- Thrombosis
- Hepatic artery thrombosis
- Kidney graft thrombosis
-
Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS)
- More common in combination with Cyclosporine
-
Angioedema
- More common in combination with ACE Inhibitors
- Serious Infections (including Polyoma Virus Infections)
- Latent Viral Infection activation
- BK virus associated nephropathy
VI. Drug Interactions
- See Cytochrome P-450 3A4
- Many Drug Interactions related to CYP3A4
- Agents that increase Purine Synthesis Inhibitor concentrations
- Linezolid potentiates myelosuppression
- Erythromycin (and Clarithromycin to a lesser extent)
- Agents that decrease Purine Synthesis Inhibitor concentrations
VII. Resources
- Sirolimus (DailyMed)
- Everolimus (DailyMed)
- Temsirolimus (DailyMed)
Images: Related links to external sites (from Bing)
Related Studies
Definition (NCI) | An ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors. |
Definition (NCI_NCI-GLOSS) | A drug used to treat advanced renal cell carcinoma (a type of kidney cancer). It is also being studied in the treatment of other types of cancer. Temsirolimus blocks a protein involved in cell division, and may kill cancer cells. It is a type of rapamycin analog and a type of serine/threonine kinase inhibitor. |
Definition (PDQ) | An ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43369&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43369&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1844" NCI Thesaurus) |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C401859 |
SnomedCT | 427153004, 427299005 |
English | 42-(3-Hydroxy-2-(hydroxymethyl)-2-methylpropanoate)rapamycin, Temsirolimus (substance), Temsirolimus, Temsirolimus (product), temsirolimus, temsirolimus [Chemical/Ingredient], TEMSIROLIMUS, temsirolimus (medication) |
Spanish | temsirolimus (sustancia), temsirolimus, temsirolimus (producto) |
Ontology: mTOR Inhibitor (C2746052)
Definition (NCI) | Any substance that inhibits mammalian target of rapamycin (mTOR or FK506 binding protein 12-rapamycin associated protein 1 (FRAP1)), a serine/threonine protein kinase that is active in the control of cell growth, cell proliferation, and cell motility. Inhibition of mTOR can inhibit cell proliferation. |
Concepts | Pharmacologic Substance (T121) |
English | mTOR Inhibitor |