U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of EVEROLIMUS

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

Description

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

Approval Year

PubMed

PubMed

TitleDatePubMed
Reduced BCL2 and CCND1 mRNA expression in human cervical cancer HeLa cells treated with a combination of everolimus and paclitaxel.
2016
Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors.
2016 Mar 15
mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.
2016 Nov
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.
Name Type Language
EVEROLIMUS
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
EVEROLIMUS [MART.]
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
SDZ-RAD
Code English
EVEROLIMUS [INN]
Common Name English
CERTICAN
Brand Name English
AFINITOR
Brand Name English
EVEROLIMUS [USAN]
Common Name English
EVEROLIMUS [MI]
Common Name English
VOTUBIA
Brand Name English
RAD-001
Code English
EVEROLIMUS [JAN]
Common Name English
EVEROLIMUS [EMA EPAR]
Common Name English
RAD 666
Code English
40-O-(2-HYDROXYETHYL)-RAPAMYCIN
Common Name English
EVEROLIMUS [VANDF]
Common Name English
EVEROLIMUS [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-ATC L04AA18
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
WHO-VATC QL04AA18
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
EMA ASSESSMENT REPORTS VOTUBIA (AUTHORIZED: TUBEROUS SCLEROSIS)
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
NDF-RT N0000175605
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
EMA ASSESSMENT REPORTS AFINITOR (AUTHORIZED: CARCINOMA, RENAL CELL)
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
WHO-ATC L01XE10
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
EMA ASSESSMENT REPORTS AFINITOR (AUTHORIZED: PANCREATIC NEOPLASMS)
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
NDF-RT N0000175076
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
WHO-VATC QL01XE10
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
LIVERTOX 393
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
Code System Code Type Description
HSDB
159351-69-6
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
MERCK INDEX
M5220
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY Merck Index
ChEMBL
CHEMBL1908360
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
NDF-RT
N0000182141
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
DRUG BANK
DB01590
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
INN
7863
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
CAS
159351-69-6
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
IUPHAR
5889
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
WIKIPEDIA
EVEROLIMUS
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
MESH
C107135
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
LactMed
159351-69-6
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
EPA CompTox
159351-69-6
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
PUBCHEM
6442177
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY SWITZERF
NDF-RT
N0000182137
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
EVMPD
SUB02065MIG
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY
NDF-RT
N0000185503
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY P-Glycoprotein Inhibitors [MoA]
RXCUI
141704
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY RxNorm
NCI_THESAURUS
C48387
Created by admin on Tue Mar 06 11:15:54 UTC 2018 , Edited by admin on Tue Mar 06 11:15:54 UTC 2018
PRIMARY