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Accession NumberDB01590
TypeSmall Molecule

Everolimus is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors Everolimus’ effect is solely on the mTORC1 protein and not on the mTORC2 protein.

AfinitorNot AvailableNot Available
CerticanNot AvailableNot Available
RAD001Not AvailableNot Available
SDZ-RADNot AvailableNot Available
VOTUBIANot AvailableNot Available
ZortressNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zortresstablet.5 mgoralNovartis Pharmaceuticals Corporation2010-04-22Not AvailableUs
Zortresstablet.75 mgoralNovartis Pharmaceuticals Corporation2010-04-22Not AvailableUs
Zortresstablet.25 mgoralNovartis Pharmaceuticals Corporation2010-04-22Not AvailableUs
Afinitortablet5 mgoralNovartis Pharmaceuticals Corporation2009-03-31Not AvailableUs
Afinitortablet10 mgoralNovartis Pharmaceuticals Corporation2009-03-31Not AvailableUs
Afinitortablet2.5 mgoralNovartis Pharmaceuticals Corporation2010-07-09Not AvailableUs
Afinitortablet7.5 mgoralNovartis Pharmaceuticals Corporation2011-07-29Not AvailableUs
Afinitor Disperztablet, for suspension2 mgoralNovartis Pharmaceuticals Corporation2012-08-29Not AvailableUs
Afinitor Disperztablet, for suspension3 mgoralNovartis Pharmaceuticals Corporation2012-08-29Not AvailableUs
Afinitor Disperztablet, for suspension5 mgoralNovartis Pharmaceuticals Corporation2012-08-29Not AvailableUs
Afinitortablet5 mgoralNovartis Pharmaceuticals Canada IncNot AvailableNot AvailableCanada
Afinitortablet10 mgoralNovartis Pharmaceuticals Canada IncNot AvailableNot AvailableCanada
Afinitortablet2.5 mgoralNovartis Pharmaceuticals Canada IncNot AvailableNot AvailableCanada
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
Brand mixturesNot Available
SaltsNot Available
CAS number159351-69-6
WeightAverage: 958.2244
Monoisotopic: 957.581356369
Chemical FormulaC53H83NO14
DescriptionThis compound belongs to the class of organic compounds known as macrolide lactams. These are cyclic polyketides containing both a cyclic amide and a cyclic ester group.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolide lactams
Sub ClassNot Available
Direct ParentMacrolide lactams
Alternative Parents
  • Macrolide lactam
  • Macrolide
  • Alpha-amino acid ester
  • Piperidine
  • Oxane
  • Tertiary carboxylic acid amide
  • Cyclic ketone
  • Tertiary amine
  • Secondary alcohol
  • Lactone
  • Lactam
  • Ketone
  • Hemiacetal
  • Carboxylic acid ester
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
IndicationEverolimus is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole. Indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease. Indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Indicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.
PharmacodynamicsNot Available
Mechanism of actionEverolimus is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake.
AbsorptionIn patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, Cmax is dose-proportional between 5 mg and 10 mg. At doses of 20 mg and higher, the increase in Cmax is less than dose-proportional, however AUC shows dose-proportionality over the 5 mg to 70 mg dose range. Steady-state was achieved within 2 weeks following once-daily dosing. Dose Proportionality in Patients with SEGA (subependymal giant-cell astrocytomas) and TSC (tuberous sclerosis complex): In patients with SEGA and TSC, everolimus Cmin was approximately dose-proportional within the dose range from 1.35 mg/m2 to 14.4 mg/m2.
Volume of distribution

The blood-to-plasma ratio of everolimus is 17% to 73%.

Protein binding~ 74% in both healthy patients and those with moderate hepatic impairment.

Everolimus is a substrate of CYP3A4 and PgP (phosphoglycolate phosphatase). Three monohydroxylated metabolites, two hydrolytic ring-opened products, and a phosphatidylcholine conjugate of everolimus were the 6 primary metabolites detected in human blood. In vitro, everolimus competitively inhibited the metabolism of CYP3A4 and was a mixed inhibitor of the CYP2D6 substrate dextromethorphan.

Route of eliminationAfter a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine.
Half life~30 hours.

Following a 3 mg radiolabeled dose of everolimus, 80% of the radioactivity was recovered from the feces, while 5% was excreted in the urine.

ToxicityIC50 of 0.63 nM.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Predicted ADMET features
Human Intestinal Absorption-0.8288
Blood Brain Barrier-0.9541
Caco-2 permeable-0.6604
P-glycoprotein substrateSubstrate0.8117
P-glycoprotein inhibitor IInhibitor0.7789
P-glycoprotein inhibitor IIInhibitor0.7294
Renal organic cation transporterNon-inhibitor0.796
CYP450 2C9 substrateNon-substrate0.8793
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.9078
CYP450 2C9 substrateNon-inhibitor0.9106
CYP450 2D6 substrateNon-inhibitor0.9388
CYP450 2C19 substrateNon-inhibitor0.9346
CYP450 3A4 substrateNon-inhibitor0.8168
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9734
Ames testNon AMES toxic0.6227
BiodegradationNot ready biodegradable0.9257
Rat acute toxicity2.7442 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9776
hERG inhibition (predictor II)Non-inhibitor0.712
ManufacturersNot Available
Dosage forms
Tabletoral.25 mg
Tabletoral.5 mg
Tabletoral.75 mg
Tabletoral10 mg
Tabletoral2.5 mg
Tabletoral5 mg
Tabletoral7.5 mg
Tablet, for suspensionoral2 mg
Tablet, for suspensionoral3 mg
Tablet, for suspensionoral5 mg
Unit descriptionCostUnit
Afinitor 10 mg tablet247.58USD tablet
Afinitor 5 mg tablet234.75USD tablet
Vesicare 10 mg tablet6.98USD tablet
Vesicare 5 mg tablet6.98USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
CountryPatent NumberApprovedExpires (estimated)
United States64409901993-09-242013-09-24
United States72977031999-12-062019-12-06
Experimental PropertiesNot Available
Predicted Properties
Water Solubility0.00163 mg/mLALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area204.66 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity261.71 m3·mol-1ChemAxon
Polarizability105.73 Å3ChemAxon
Number of Rings4ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Mass Spec (NIST)Download (87.7 KB)
SpectraNot Available
Synthesis Reference
General Reference
  1. Kuhn B, Jacobsen W, Christians U, Benet LZ, Kollman PA: Metabolism of sirolimus and its derivative everolimus by cytochrome P450 3A4: insights from docking, molecular dynamics, and quantum chemical calculations. J Med Chem. 2001 Jun 7;44(12):2027-34. Pubmed
  2. Pubmed
  3. Pubmed
  4. Pubmed
External Links
ATC CodesL01XE10L04AA18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (548 KB)
MSDSDownload (220 KB)
Drug Interactions
BicalutamideCYP3A4 Inhibitors like bicalutamide may increase the serum concentration of everolimus. Consider therapy modification. Recommendations regarding optimal management of this interaction vary according to specific indication and product used.
ClarithromycinThe macrolide, clarithromycin, may increase the serum concentration and toxicity of everolimus.
ClotrimazoleCYP3A4 Inhibitors (Moderate)such as clotrimazole may increase the serum concentration of everolimus. The prescribing information for the Afinitor branded everolimus product lists indication-specific recommendations for managing this interaction.
ConivaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Everolimus prescribing information recommends avoiding concurrent use with strong CYP3A4 inhbitors.
ErythromycinThe macrolide, erythromycin, may increase the serum concentration and toxicity of everolimus.
EtravirineEverolimus, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid this combination. If concurrent therapy cannot be avoided, a gradual dosage increase of everolimus is recommended.
FluconazoleFluconazole may increase everolimus levels/toxicity.
ItraconazoleItraconazole may increase everolimus levels/toxicity.
KetoconazoleKetoconazole may increase everolimus levels/toxicity.
Rilonaceptresults in increased immunosuppressive effects; increases the risk of infection.
VerapamilConcomitant administration may increase the serum concentrations of both agents. Concurrent use should be avoided.
VoriconazoleVoriconzole, a strong CYP3A4 inhibitor, may increase the serum concentration of everolimus by decreasing its metabolism. Concurrent therapy should be avoided.
Food InteractionsNot Available


1. Serine/threonine-protein kinase mTOR

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor


Name UniProt ID Details
Serine/threonine-protein kinase mTOR P42345 Details


  1. Ettenger R, Hoyer PF, Grimm P, Webb N, Loirat C, Mahan JD, Mentser M, Niaudet P, Offner G, Vandamme-Lombaerts R, Hexham JM: Multicenter trial of everolimus in pediatric renal transplant recipients: results at three year. Pediatr Transplant. 2008 Jun;12(4):456-63. Pubmed
  2. Rostaing L, Kamar N: mTOR inhibitor/proliferation signal inhibitors: entering or leaving the field? J Nephrol. 2010 Mar-Apr;23(2):133-42. Pubmed
  3. George S, Bukowski RM: Role of everolimus in the treatment of renal cell carcinoma. Ther Clin Risk Manag. 2009 Oct;5(5):699-706. Epub 2009 Sep 15. Pubmed
  4. Teachey DT, Grupp SA, Brown VI: Mammalian target of rapamycin inhibitors and their potential role in therapy in leukaemia and other haematological malignancies. Br J Haematol. 2009 Jun;145(5):569-80. Epub 2009 Mar 16. Pubmed
  5. Albert S, Serova M, Dreyer C, Sablin MP, Faivre S, Raymond E: New inhibitors of the mammalian target of rapamycin signaling pathway for cancer. Expert Opin Investig Drugs. 2010 Jun 23. Pubmed
  6. Coppin C: Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib. Biologics. 2010 May 25;4:91-101. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed


1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate


Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details


  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on August 29, 2007 09:37 / Updated on September 16, 2013 17:15