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Details

Stereochemistry ABSOLUTE
Molecular Formula C56H87NO16
Molecular Weight 1030.2871
Optical Activity UNSPECIFIED
Defined Stereocenters 15 / 15
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TEMSIROLIMUS

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]1OC(=O)C(C)(CO)CO

InChI

InChIKey=CBPNZQVSJQDFBE-FUXHJELOSA-N
InChI=1S/C56H87NO16/c1-33-17-13-12-14-18-34(2)45(68-9)29-41-22-20-39(7)56(67,73-41)51(63)52(64)57-24-16-15-19-42(57)53(65)71-46(30-43(60)35(3)26-38(6)49(62)50(70-11)48(61)37(5)25-33)36(4)27-40-21-23-44(47(28-40)69-10)72-54(66)55(8,31-58)32-59/h12-14,17-18,26,33,35-37,39-42,44-47,49-50,58-59,62,67H,15-16,19-25,27-32H2,1-11H3/b14-12+,17-13+,34-18+,38-26+/t33-,35-,36-,37-,39-,40+,41+,42+,44-,45+,46+,47-,49-,50+,56-/m1/s1

HIDE SMILES / InChI

Molecular Formula C56H87NO16
Molecular Weight 1030.2871
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 15 / 15
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Temsirolimus is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the FDA in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007. It is a derivative of sirolimus and is sold as Torisel. Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomal protein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. In in vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and the vascular endothelial growth factor.

Originator

Approval Year

TargetsConditions
PubMed

PubMed

TitleDatePubMed
Dual blockade of PI3K/AKT/mTOR (NVP-BEZ235) and Ras/Raf/MEK (AZD6244) pathways synergistically inhibit growth of primary endometrioid endometrial carcinoma cultures, whereas NVP-BEZ235 reduces tumor growth in the corresponding xenograft models.
2015 Jul
Targeting Survivin Inhibits Renal Cell Carcinoma Progression and Enhances the Activity of Temsirolimus.
2015 Jun
Effect of Targeting Clusterin Using OGX-011 on Antitumor Activity of Temsirolimus in a Human Renal Cell Carcinoma Model.
2017 Feb
Patents

Sample Use Guides

In Vivo Use Guide
Renal Cell Carcinoma General Dosage IV 25 mg once weekly.
Route of Administration: Intravenous
In Vitro Use Guide
Temsirolimus (10uM) inhibited the growth of Human Renal Cell Carcinoma Caki-1 growth approx. by 60%
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:44:58 UTC 2019
Edited
by admin
on Mon Oct 21 20:44:58 UTC 2019
Record UNII
624KN6GM2T
Record Status Validated (UNII)
Record Version
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Name Type Language
TEMSIROLIMUS
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
TEMSIROLIMUS [VANDF]
Common Name English
RAPAMYCIN 42-(2,2-BIS(HYDROXYMETHYL)PROPIONATE)
Common Name English
TORISEL
Brand Name English
TEMSIROLIMUS [JAN]
Common Name English
TEMSIROLIMUS [EMA EPAR]
Common Name English
TEMSIROLIMUS [ORANGE BOOK]
Common Name English
TEMSIROLIMUS [USAN]
Common Name English
TEMSIROLIMUS [WHO-DD]
Common Name English
TEMSIROLIMUS [INN]
Common Name English
RAPAMYCIN, 42-(3-HYDROXY-2-(HYDROXYMETHYL)-2-METHYLPROPANOATE)
Common Name English
CCI-779
Code English
TEMSIROLIMUS [MI]
Common Name English
TEMSIROLIMUS [MART.]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175076
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
EMA ASSESSMENT REPORTS TORISEL (AUTHORIZED: LYMPHOMA, MANTLE-CELL)
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
EMA ASSESSMENT REPORTS TORISEL (AUTHORIZED: CARCINOMA, RENAL CELL)
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
NCI_THESAURUS C2201
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
FDA ORPHAN DRUG 196404
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
LIVERTOX 933
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
WHO-ATC L01XE09
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
WHO-VATC QL01XE09
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
EU-Orphan Drug EU/3/06/365
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
Code System Code Type Description
EVMPD
SUB21308
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
IUPHAR
5892
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
HSDB
162635-04-3
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
DRUG BANK
DB06287
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
LactMed
162635-04-3
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
INN
8212
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
MERCK INDEX
M10555
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY Merck Index
MESH
C401859
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
PUBCHEM
6918289
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
WIKIPEDIA
Temsirolimus
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
ChEMBL
CHEMBL1201182
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
CAS
162635-04-3
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
EPA CompTox
162635-04-3
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
NCI_THESAURUS
C1844
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY
RXCUI
657797
Created by admin on Mon Oct 21 20:44:58 UTC 2019 , Edited by admin on Mon Oct 21 20:44:58 UTC 2019
PRIMARY RxNorm
Related Record Type Details
METABOLIC ENZYME -> INHIBITOR
IC50
METABOLIC ENZYME -> INHIBITOR
IC50
METABOLIC ENZYME -> INHIBITOR
IC50
BINDER->LIGAND
The percentage of [14C]temsirolimus bound to proteins at concentrations of 100 ng/mL when calculated for undiluted human plasma in erythrocyte suspensions was 87.1%.
BINDING
METABOLIC ENZYME -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
BINDER->LIGAND
The percentage of [14C]temsirolimus bound to proteins at concentrations of 10 ng/mL when calculated for undiluted human plasma in erythrocyte suspensions was 85.0%
BINDING
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

SINGLE DOSE