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

Details

Stereochemistry ABSOLUTE
Molecular Formula C53H84NO14P
Molecular Weight 990.2082
Optical Activity UNSPECIFIED
Defined Stereocenters 15 / 15
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RIDAFOROLIMUS

SMILES

C[C@]1([H])/C(/[H])=C(\[H])/C(/[H])=C(\[H])/C(/[H])=C(\C)/[C@]([H])(C[C@]2([H])CC[C@@]([H])(C)[C@@](C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O[C@@]([H])(CC(=O)[C@]([H])(C)/C(/[H])=C(\C)/[C@]([H])([C@]([H])(C(=O)[C@]([H])(C)C1)OC)O)[C@]([H])(C)C[C@]4([H])CC[C@]([H])([C@@]([H])(C4)OC)OP(=O)(C)C)(O)O2)OC

InChI

InChIKey=BUROJSBIWGDYCN-GAUTUEMISA-N
InChI=1S/C53H84NO14P/c1-32-18-14-13-15-19-33(2)44(63-8)30-40-23-21-38(7)53(61,67-40)50(58)51(59)54-25-17-16-20-41(54)52(60)66-45(35(4)28-39-22-24-43(46(29-39)64-9)68-69(11,12)62)31-42(55)34(3)27-37(6)48(57)49(65-10)47(56)36(5)26-32/h13-15,18-19,27,32,34-36,38-41,43-46,48-49,57,61H,16-17,20-26,28-31H2,1-12H3/b15-13+,18-14+,33-19+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/history/ridaforolimus.html https://www.ncbi.nlm.nih.gov/pubmed/20945947

Ridaforolimus (Deforolimus, MK-8669) is an investigational oral mTOR inhibitor in development for the treatment of metastatic soft-tissue or bone sarcomas. Ridaforolimus is being co-developed by Merck and ARIAD Pharmaceuticals. Ridaforolimus (Deforolimus, MK-8669) is a selective mTOR inhibitor with IC50 of 0.2 nM in HT-1080 cell line; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. mTOR is a protein kinase that controls cell growth by regulating many cellular processes, including protein synthesis and autophagy. Compared with other mTOR inhibitors, ridaforolimus is not a prodrug and has shown in vivo stability. Both intravenous and oral formulations of the compound are being tested in clinical trials for the treatment of various solid tumors and hematologic malignancies. The initial indication is soft-tissue and bone sarcomas. Ridaforolimus was indicated to treat patients with metastatic soft tissue sarcoma or bone sarcoma whose disease has not progressed after at least 4 cycles of chemotherapy. In June 2012, Merck & Co., Inc. announced the receipt of a Complete Response Letter from the U.S. Food and Drug Administration (FDA), advising the company that the New Drug Application (NDA) for ridaforolimus had not been approved. Currently Ridaforolimus is in phase III clinical trials for the treatment of Coronary artery restenosis.

CNS Activity

Curator's Comment:: Ridaforolimus can cross the blood-brain barrier in areas of tumor involvement, and may inhibit mTOR activity in advanced gliomas based on decreased pS6 levels.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Ridaforolimus.
2010
Targeting the PI3K/PTEN/AKT/mTOR Pathway in Treatment of Sarcoma Cell Lines.
2016 Nov
Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer.
2016 Oct 20
Patents

Sample Use Guides

Treatment of HT-1080 cells with Deforolimus induces a dose-dependent inhibition of phosphorylation of both S6 and 4E-BP1, with IC50 of 0.2 nM and 5.6 nM, respectively, and leads to a decrease in cell size, an increase in the proportion of cells in the G1 phase of the cell cycle, and inhibition of glucose uptake. Deforolimus displays significant antiproliferative activity a broad panel of cell lines with EC50 of 0.2-2.3 nM.
Name Type Language
RIDAFOROLIMUS
INN   MART.   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
DEFOROLIMUS
Common Name English
RIDAFOROLIMUS [USAN]
Common Name English
AP23573
Code English
AP 23573
Code English
RIDAFOROLIMUS [INN]
Common Name English
RIDAFOROLIMUS [JAN]
Common Name English
AP-23573
Code English
RIDAFOROLIMUS [MI]
Common Name English
MK-8669
Code English
RIDAFOROLIMUS [MART.]
Common Name English
RIDAFOROLIMUS [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 207805
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
WHO-VATC QL01XE19
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
FDA ORPHAN DRUG 207705
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
NCI_THESAURUS C2201
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
WHO-ATC L01XE19
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
Code System Code Type Description
CAS
572924-54-0
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
NCI_THESAURUS
C49061
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
PUBCHEM
11520894
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
ChEMBL
CHEMBL2103839
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
FDA UNII
48Z35KB15K
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
DRUG CENTRAL
4778
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
WIKIPEDIA
RIDAFOROLIMUS
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
DRUG BANK
DB06233
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
EVMPD
SUB32091
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
INN
8822
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY
MERCK INDEX
M9606
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY Merck Index
MESH
C515074
Created by admin on Sat Jun 26 15:22:14 UTC 2021 , Edited by admin on Sat Jun 26 15:22:14 UTC 2021
PRIMARY