RIDAFOROLIMUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C53H84NO14P
Molecular Weight	990.2061
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]1OP(C)(C)=O

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

Molecular Formula	C53H84NO14P
Molecular Weight	990.2061
Charge	0
Count

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

Description
Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM296304.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM296304.pdf	Inhibitor 8504		0.2 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sarcoma 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00538239	Primary		Phase III 665	Unknown Approved Use Unknown
Coronary artery restenosis 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02736344	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
101.19 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s00280-013-2250-6	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		RIDAFOROLIMUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
82.66 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s00280-013-2250-6	30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
139 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	22 mg 1 times / day steady-state, oral dose: 22 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
228 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	28 mg 1 times / day steady-state, oral dose: 28 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
200 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	33 mg 1 times / day steady-state, oral dose: 33 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
55.2 ng/mL EXPERIMENT https://www.annalsofoncology.org/article/S0923-7534(19)37208-4/fulltext	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
105 ng/mL EXPERIMENT https://www.annalsofoncology.org/article/S0923-7534(19)37208-4/fulltext	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
853.68 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s00280-013-2250-6	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		RIDAFOROLIMUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
735.42 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s00280-013-2250-6	30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1340 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	22 mg 1 times / day steady-state, oral dose: 22 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
2330 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	28 mg 1 times / day steady-state, oral dose: 28 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
2280 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	33 mg 1 times / day steady-state, oral dose: 33 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
696 ng × h/mL EXPERIMENT https://www.annalsofoncology.org/article/S0923-7534(19)37208-4/fulltext	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1858 ng × h/mL EXPERIMENT https://www.annalsofoncology.org/article/S0923-7534(19)37208-4/fulltext	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
25.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	22 mg 1 times / day steady-state, oral dose: 22 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
28.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	28 mg 1 times / day steady-state, oral dose: 28 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
26.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356695/	33 mg 1 times / day steady-state, oral dose: 33 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
33.6 h EXPERIMENT https://www.annalsofoncology.org/article/S0923-7534(19)37208-4/fulltext	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
58.4 h EXPERIMENT https://www.annalsofoncology.org/article/S0923-7534(19)37208-4/fulltext	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered: BICALUTAMIDE	BICALUTAMIDE	RIDAFOROLIMUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Targeting the PI3K/PTEN/AKT/mTOR Pathway in Treatment of Sarcoma Cell Lines.	2016-11	27793898
Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer.	2016-10-20	27765027
Ridaforolimus.	2010	20945947

Patents

Sample Use Guides

In Vivo Use Guide

40 mg po 5 days/week

Route of Administration: Oral

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:01:38 GMT 2025` Edited by `admin` on `Mon Mar 31 18:01:38 GMT 2025`
Record UNII	48Z35KB15K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RIDAFOROLIMUS [MI]

Preferred Name

English

RIDAFOROLIMUS

Official Name

English

Ridaforolimus [WHO-DD]

Common Name

English

DEFOROLIMUS

Common Name

English

RIDAFOROLIMUS [USAN]

Common Name

English

AP23573

Code

English

MK8669

Code

English

ridaforolimus [INN]

Common Name

English

RIDAFOROLIMUS [JAN]

Common Name

English

AP-23573

Code

English

MK-8669

Code

English

RIDAFOROLIMUS [MART.]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

207805