Everolimus

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C53H83NO14
Molecular Weight	958.2244
Optical Activity	UNSPECIFIED
Defined Stereocenters	15 / 15
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@@H]1C[C@H](C[C@@H](C)[C@@H]2CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@@H]3CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N4CCCC[C@H]4C(=O)O2)OC)CC[C@H]1OCCO

InChI

InChIKey=HKVAMNSJSFKALM-GKUWKFKPSA-N

InChI=1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11+,16-12+,33-17+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C53H83NO14
Molecular Weight	958.2244
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	15 / 15
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB01590
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022334s036lbl.pdf

Everolimus is a derivative of Rapamycin (sirolimus), it 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. Everolimus 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. Everolimus is marketed by Novartis under the tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine, and as Afinitor (general tumours) and Votubia (tumours as a result of TSC) in oncology. Everolimus is also available from Biocon, with the brand name Evertor, from Natco Pharma, with the brand name Temonat, from Ranbaxy Laboratories, with the brand name of Imozide, from Emcure Pharmaceuticals, with the brand name of Temcure, among over 20 different brands.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: http://www.drugbank.ca/drugs/DB01590	Inhibitor 8504
osteoblast differentiation 1 Target ID: GO:0001649 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15542040	Inhibitor 8504		13.5 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Advanced hormone receptor-positive, HER2 negative breast cancer 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022334s036lbl.pdf	Primary	Approved 8583	AFINITOR Approved Use AFINITOR is a kinase inhibitor 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. adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Launch Date 2009
Neuroendocrine tumors 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022334s036lbl.pdf	Primary	Approved 8583	AFINITOR Approved Use AFINITOR is a kinase inhibitor 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. adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Launch Date 2009
Advanced renal cell carcinoma 9 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022334s036lbl.pdf	Primary	Approved 8583	AFINITOR Approved Use AFINITOR is a kinase inhibitor 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. adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Launch Date 2009

C_max

Value	Dose	Co-administered	Analyte	Population
18.84 ng/mL EXPERIMENT https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.e13157	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		EVEROLIMUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
61.5 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28762135	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EVEROLIMUS blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
435 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28762135	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EVEROLIMUS blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
45.74 h EXPERIMENT https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.e13157	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		EVEROLIMUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
27% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27299325			EVEROLIMUS plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193 inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 227 P-gp 1741 CYP1A2 2153 CYP2E1 1060 CYP2C8 1057 CYP2C19 2057	P-gp 2052 CYP1A1 389 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1119 CYP2E1 729 CYP3A5 446

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=25 Page: -	yes [IC50 9.42 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=6 Page: -	yes [Ki 1.7 uM]	unlikely Comment: In vitro everolimus inhibited CYP3A and 2D6, however, based on Ki values a significant effect on the metabolism of CYP3A or 2D6 is not expected. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=6 Page: -
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=6 Page: -	yes [Ki 2.3 uM]	unlikely Comment: In vitro everolimus inhibited CYP3A and 2D6, however, based on Ki values a significant effect on the metabolism of CYP3A or 2D6 is not expected. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=6 Page: -

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 389	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=26 Page: -	no
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=5 Page: -	yes	yes (co-administration study) Comment: Based on the results from the drug-drug interaction studies with ketoconazole, erythromycin and verapamil no dose adjustments wil be provided in the label since the increases in everolimus exposures can not be adjusted by lowering the dose to 5 mg QD. For strong CYP3A4 inducers, a dose increase to 20 mg would compensate for the decrease in everolimus exposure. For strong CYP3A4 inhibitors because of the significant increase in exposure labeling instructions co-administration is not recom Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=5 Page: -
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=6 Page: -	yes	yes (co-administration study) Comment: verapamil increase AUC 240% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf#page=6 Page: -

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_PharmR.pdf#page=27 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68478	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68478
ChemicalBook	CB9502411	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9502411
eMolecules	30512895	https://www.emolecules.com/cgi-bin/more?vid=30512895
eMolecules	36756561	https://www.emolecules.com/cgi-bin/more?vid=36756561
MolPort	MolPort-003-847-342	https://www.molport.com/shop/molecule-link/MolPort-003-847-342
ZINC	ZINC000169677008	http://zinc15.docking.org/substances/ZINC000169677008

PubMed

Title	Date	PubMed
Reduced BCL2 and CCND1 mRNA expression in human cervical cancer HeLa cells treated with a combination of everolimus and paclitaxel.	2016	27095936
Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors.	2016 Mar 15	26978006
mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.	2016 Nov	27697900

Patents

Sample Use Guides

In Vivo Use Guide

Advanced HR+ BC, advanced NET, advanced RCC, or renal angiomyolipoma with TSC: 10 mg once daily with or without food.

Route of Administration: Oral

In Vitro Use Guide

Everolimus effectively inhibited cell growth at concentrations under 100 nM (IC(50)) in five triple-negative breast cancers cell lines and even in the 1-nM range in three of the five cell lines.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:49:49 GMT 2025` Edited by `admin` on `Wed Apr 02 08:49:49 GMT 2025`
Record UNII	9HW64Q8G6G
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

AFINITOR

Preferred Name

English

Everolimus

Official Name

English

EVEROLIMUS [MART.]

Common Name

English

Rapamycin, 42-O-(2-hydroxyethyl)-

Common Name

English

RAD-666

Code

English

SDZ RAD

Common Name

English

EVEROLIMUS [ORANGE BOOK]

Common Name

English

ZORTRESS

Brand Name

English

RAD001

Code

English

EVEROLIMUS [USP-RS]

Common Name

English

SDZ-RAD

Code

English

everolimus [INN]

Common Name

English

(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-[(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]-1-methylethyl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0<sup>4,9</sup>]hexatr

Systematic Name

English

CERTICAN

Brand Name

English

EVEROLIMUS [EP MONOGRAPH]

Common Name

English

EVEROLIMUS [USAN]

Common Name

English

EVEROLIMUS [MI]

Common Name

English

Everolimus [WHO-DD]

Common Name

English

VOTUBIA

Brand Name

English

RAD-001

Code

English

EVEROLIMUS [JAN]

Common Name

English

EVEROLIMUS [EMA EPAR]

Common Name

English

(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexameth

Systematic Name

English

RAD 666

Code

English

42-O-(2-Hydroxyethyl)rapamycin

Common Name

English

EVEROLIMUS [VANDF]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

374012