Ridaforolimus

Summary

Ridaforolimus (CHEMBL2103839) is a phase-3 clinical-stage small molecule (ATC L01EG03) targeting MTOR; indicated across 19 conditions including neoplasm and sarcoma; with CIViC clinical evidence for 3 variant-indication associations (e.g. KRAS Mutation in endometrial cancer).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: L01EG03
• Targets: 1 (MTOR)
• Indications: 19 conditions
• Clinical trials: 35
• Precision-oncology evidence (CIViC): 3 variant–indication associations
• Chemistry: 990.2 Da · C53H84NO14P

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2103839
Name	Ridaforolimus
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11520894
ATC	L01EG03
Molecular formula	C53H84NO14P
Molecular weight	990.2
InChIKey	BUROJSBIWGDYCN-GAUTUEMISA-N

SMILES: C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)OP(=O)(C)C)C)/C)O)OC)C)C)/C)OC

IUPAC name: (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-12-[(2R)-1-[(1S,3R,4R)-4-dimethylphosphoryloxy-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone

Also known as: AP 23573, AP-23573, AP23573, MK-8669, MK8669, Ridaforolimus, RIDAFOROLIMUS, Deforolimus, Ridaforolimus; Deforolimus

Patent coverage: 2,683 distinct patent families (6,695 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
MTOR	mechanistic target of rapamycin kinase	Inhibition	9.7	98.3% (common-essential)	P42345

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Dual specificity tyrosine-phosphorylation-regulated kinase 1B.

Bioactivity

ChEMBL activities: 1 potent at pChembl ≥ 5 of 1 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DYRK1B	5.9	Kd	1262	nM	CHEMBL_ACT_17898274

Target pathways

Aggregated over 1 target gene(s): MTOR.

Top Reactome pathways

41 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	1	MTOR
Adaptive Immune System	1	MTOR
Signal Transduction	1	MTOR
Macroautophagy	1	MTOR
Disease	1	MTOR
MTOR signalling	1	MTOR
mTORC1-mediated signalling	1	MTOR
Immune System	1	MTOR
Signaling by VEGF	1	MTOR
Generic Transcription Pathway	1	MTOR
PI3K/AKT Signaling in Cancer	1	MTOR
Cellular responses to stress	1	MTOR
Cellular response to heat stress	1	MTOR
HSF1-dependent transactivation	1	MTOR
Transcriptional Regulation by TP53	1	MTOR
Energy dependent regulation of mTOR by LKB1-AMPK	1	MTOR
Regulation of T cell activation by CD28 family	1	MTOR
Co-stimulation by CD28	1	MTOR
CD28 dependent PI3K/Akt signaling	1	MTOR
VEGFA-VEGFR2 Pathway	1	MTOR
VEGFR2 mediated vascular permeability	1	MTOR
TP53 Regulates Metabolic Genes	1	MTOR
Regulation of TP53 Activity	1	MTOR
Diseases of signal transduction by growth factor receptors and second messengers	1	MTOR
Constitutive Signaling by AKT1 E17K in Cancer	1	MTOR
Regulation of TP53 Degradation	1	MTOR
Regulation of TP53 Expression and Degradation	1	MTOR
PTEN Regulation	1	MTOR
RNA Polymerase II Transcription	1	MTOR
Gene expression (Transcription)	1	MTOR
Regulation of PTEN gene transcription	1	MTOR
Cellular responses to stimuli	1	MTOR
Intracellular signaling by second messengers	1	MTOR
Signaling by Receptor Tyrosine Kinases	1	MTOR
Autophagy	1	MTOR
Amino acids regulate mTORC1	1	MTOR
Cellular response to starvation	1	MTOR
Cellular responses to mechanical stimuli	1	MTOR
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	MTOR
Response of endothelial cells to shear stress	1	MTOR
Dengue virus modulates apoptosis	1	MTOR

Dominant GO biological processes

GO term	Targets
regulation of cell growth	1
T-helper 1 cell lineage commitment	1
heart morphogenesis	1
heart valve morphogenesis	1
energy reserve metabolic process	1
‘de novo’ pyrimidine nucleobase biosynthetic process	1
inflammatory response	1
DNA damage response	1
cytoskeleton organization	1
germ cell development	1
regulation of cell size	1
cellular response to starvation	1
response to heat	1
response to virus	1
post-embryonic development	1

Indications & clinical

Indications

15 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
neoplasm	3	MONDO:0005070	EFO:0000616
sarcoma	3	MONDO:0005089	EFO:0000691
osteosarcoma	3	MONDO:0009807	EFO:0000637
soft tissue sarcoma	3	MONDO:0018078	EFO:1001968
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
myelodysplastic syndrome	2	MONDO:0018881	EFO:0000198
leiomyosarcoma	2	MONDO:0005058	EFO:0000564
leukemia	2	MONDO:0005059	EFO:0000565
liposarcoma	2	MONDO:0005060	EFO:0000569
lymphoma	2	MONDO:0005062	EFO:0000574
primary myelofibrosis	2	MONDO:0009692	EFO:0002430
breast neoplasm	2	MONDO:0021100	EFO:0003869
endometrium neoplasm	2	MONDO:0021251	MONDO:0011962
gliosarcoma	1	MONDO:0016681	EFO:1001465
plasma cell myeloma	1	MONDO:0009693	EFO:0001378

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 35.

Phase distribution

Phase	Trials
PHASE1	21
PHASE2	13
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00538239	PHASE3	COMPLETED	Ridaforolimus in Treatment of Sarcoma-SUCCEED (Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Ridaforolimus)(8669-011 AM6)
NCT00086125	PHASE2	COMPLETED	Study of AP23573 in Patients With Relapsed or Refractory Hematologic Malignancies (8669-024)(COMPLETED)
NCT00093080	PHASE2	COMPLETED	Study of AP23573/MK-8669 (Ridaforolimus), A Mammalian Target of Rapamycin (mTOR) Inhibitor, in Participants With Advanced Sarcoma (MK-8669-018 AM1)(COMPLETED)
NCT00110188	PHASE2	COMPLETED	Ridaforolimus (AP23573/MK-8669) in Participants With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)(MK-8669-017)
NCT00122343	PHASE2	COMPLETED	AP23573 in Female Adult Patients With Recurrent or Persistent Endometrial Cancer (8669-019)(COMPLETED)
NCT00736970	PHASE2	COMPLETED	Oral Deforolimus With Trastuzumab for Patients With HER2-positive Trastuzumab-Refractory Metastatic Breast Cancer (8669-009)
NCT00739830	PHASE2	COMPLETED	Clinical Trial of Ridaforolimus Compared to Progestin or Chemotherapy for Advanced Endometrial Carcinoma (MK-8669-007 AM6)
NCT00770185	PHASE2	COMPLETED	Ridaforolimus in Treating Patients With Recurrent Metastatic and/or Locally Advanced Endometrial Cancer
NCT00777959	PHASE2	COMPLETED	Bicalutamide and Ridaforolimus in Men With Prostate Cancer (MK-8669-002)
NCT00818675	PHASE2	TERMINATED	A Study of Ridaforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations (MK-8669-021 AM1)
NCT00836927	PHASE2	TERMINATED	Extension Trial of Deforolimus (Ridaforolimus, MK-8669) in Participants With Advanced Cancer (MK-8669-038)
NCT01010672	PHASE2	COMPLETED	Phase II Study of Ridaforolimus (MK-8669) With Metastatic Bone or Soft-tissue Sarcoma Patients (MK-8669-030 AM1)
NCT01234857	PHASE2	COMPLETED	A Study of Ridaforolimus (MK-8669) in Combination With Dalotuzumab (MK-0646) Compared to Standard of Care Treatment in Estrogen Receptor Positive Breast Cancer Patients (MK-8669-041 AM3)
NCT01605396	PHASE2	COMPLETED	A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)
NCT00060632	PHASE1	COMPLETED	Safety Study of Ridaforolimus in Patients With Advanced, Refractory or Recurrent Malignancies (MK-8669-001 AM5)(COMPLETED)
NCT00060645	PHASE1	COMPLETED	Safety Study of AP23573 in Patients With Advanced, Refractory or Recurrent Malignancies (8669-013)(COMPLETED)
NCT00087451	PHASE1	COMPLETED	Safety Study of AP23573 in Patients With Progressive or Recurrent Glioma (8669-023)(COMPLETED)
NCT00112372	PHASE1	COMPLETED	Study of Oral Ridaforolimus (AP23573, MK-8669) to Treat Patients With Refractory or Advanced Malignancies (MK-8669-016 AM4)(COMPLETED)
NCT00288431	PHASE1	COMPLETED	Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin (8669-015)
NCT00694083	PHASE1	COMPLETED	Study of Ridaforolimus (MK-8669) in Participants With Solid Tumors (MK-8669-003)(COMPLETED)
NCT00704054	PHASE1	COMPLETED	A Multi-Center Phase I Study of Intravenous Deforolimus (AP23573, MK-8669) Administered QDX5 Every Other Week in Pediatric Patients With Advanced Solid Tumors (8669-028)(COMPLETED)
NCT00781846	PHASE1	COMPLETED	Trial of Deforolimus in Combination With Bevacizumab for Patients With Advanced Cancers (8669-010)(COMPLETED)
NCT00874731	PHASE1	COMPLETED	A Study to Evaluate the Effect of MK-8669 (Ridaforolimus) on QTc Interval in Participants With Advanced Cancer (MK-8669-037)
NCT01043887	PHASE1	COMPLETED	Ridaforolimus in Patients With Hepatic Insufficiency (MK-8669-046)
NCT01071304	PHASE1	COMPLETED	Effect of Ridaforolimus on the Pharmacokinetics of Midazolam (Study MK-8669-044)
NCT01169532	PHASE1	COMPLETED	Ridaforolimus and Vorinostat in Treating Patients With Advanced Solid Tumors or Lymphoma
NCT01212627	PHASE1	TERMINATED	Ridaforolimus With Cetuximab: Adv Non-Small Cell Lung, Colorectal, Head & Neck Cancer
NCT01220570	PHASE1	COMPLETED	The Growth Factor Signature (GFS) as an Intermediate Biomarker of Response for Development of PI3K-Pathway Inhibitors in Patients With Breast Cancer (MK-8669-050)
NCT01243762	PHASE1	TERMINATED	A Study of Dalotuzumab + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + Ridaforolimus Combination Therapies in Participants With Advanced Cancer (MK-0646-027)
NCT01256268	PHASE1	COMPLETED	Carboplatin/Taxol/Ridaforolimus in Endometrial, Ovarian and Solids
NCT01295632	PHASE1	COMPLETED	Safety and Tolerability of Different Dose Combinations of Ridaforolimus With MK-2206 or MK-0752 for Participants With Advanced Cancer (MK-8669-049)
NCT01296659	PHASE1	WITHDRAWN	Study of Oral Ridaforolimus in Combination With Standard Chemotherapy for Soft Tissue Sarcoma
NCT01380184	PHASE1	COMPLETED	Pharmacokinetics of Ridaforolimus (MK-8669) in Chinese Participants (MK-8669-059)
NCT01431534	PHASE1	TERMINATED	A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056)
NCT01431547	PHASE1	COMPLETED	Study of Dalotuzumab Alone and With Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-062 AM1)

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
KRAS Mutation	Endometrial Cancer	Sensitivity/Response	Ridaforolimus + Temsirolimus	CIViC B	EID894
PIK3CA Mutation	Endometrial Cancer	Sensitivity/Response	Temsirolimus + Ridaforolimus	CIViC B	EID892
PTEN Loss	Endometrial Cancer	Resistance	Temsirolimus + Ridaforolimus	CIViC B	EID893

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

159 molecules share ≥1 primary target. Top 100 by shared-target count:

Molecule	Source	Status	Shared targets
ALPELISIB	ChEMBL	Phase 4 (approved)	MTOR
AMIODARONE	ChEMBL	Phase 4 (approved)	MTOR
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	MTOR
AMOXAPINE	ChEMBL	Phase 4 (approved)	MTOR
AMSACRINE	ChEMBL	Phase 4 (approved)	MTOR
AZACITIDINE	ChEMBL	Phase 4 (approved)	MTOR
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	MTOR
CARVEDILOL	ChEMBL	Phase 4 (approved)	MTOR
CHLOROQUINE	ChEMBL	Phase 4 (approved)	MTOR
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	MTOR
CLEMASTINE	ChEMBL	Phase 4 (approved)	MTOR
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	MTOR
COPANLISIB	ChEMBL	Phase 4 (approved)	MTOR
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	MTOR
CYCLOSPORINE	ChEMBL	Phase 4 (approved)	MTOR
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	MTOR
CYTARABINE	ChEMBL	Phase 4 (approved)	MTOR
DASATINIB	ChEMBL	Phase 4 (approved)	MTOR
DEQUALINIUM	ChEMBL	Phase 4 (approved)	MTOR
DESIPRAMINE	ChEMBL	Phase 4 (approved)	MTOR
DISULFIRAM	ChEMBL	Phase 4 (approved)	MTOR
DOMPERIDONE	ChEMBL	Phase 4 (approved)	MTOR
DOPAMINE	ChEMBL	Phase 4 (approved)	MTOR
DOXAZOSIN	ChEMBL	Phase 4 (approved)	MTOR
EBASTINE	ChEMBL	Phase 4 (approved)	MTOR
EMETINE	ChEMBL	Phase 4 (approved)	MTOR
EPINEPHRINE	ChEMBL	Phase 4 (approved)	MTOR
EVEROLIMUS	ChEMBL	Phase 4 (approved)	MTOR
FELODIPINE	ChEMBL	Phase 4 (approved)	MTOR
FENOFIBRATE	ChEMBL	Phase 4 (approved)	MTOR
FLUOROURACIL	ChEMBL	Phase 4 (approved)	MTOR
FLUOXETINE	ChEMBL	Phase 4 (approved)	MTOR
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	MTOR
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	MTOR
GUANABENZ	ChEMBL	Phase 4 (approved)	MTOR
HALOPERIDOL	ChEMBL	Phase 4 (approved)	MTOR
HYDROQUINONE	ChEMBL	Phase 4 (approved)	MTOR
IDARUBICIN	ChEMBL	Phase 4 (approved)	MTOR
IMIPRAMINE	ChEMBL	Phase 4 (approved)	MTOR
INDOMETHACIN	ChEMBL	Phase 4 (approved)	MTOR
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	MTOR
ISOTRETINOIN	ChEMBL	Phase 4 (approved)	MTOR
LOPERAMIDE	ChEMBL	Phase 4 (approved)	MTOR
LORATADINE	ChEMBL	Phase 4 (approved)	MTOR
MAPROTILINE	ChEMBL	Phase 4 (approved)	MTOR
MASOPROCOL	ChEMBL	Phase 4 (approved)	MTOR
MEMANTINE	ChEMBL	Phase 4 (approved)	MTOR
METHYLDOPA	ChEMBL	Phase 4 (approved)	MTOR
MIBEFRADIL	ChEMBL	Phase 4 (approved)	MTOR
MIFEPRISTONE	ChEMBL	Phase 4 (approved)	MTOR
MITOXANTRONE	ChEMBL	Phase 4 (approved)	MTOR
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	MTOR
NICARDIPINE	ChEMBL	Phase 4 (approved)	MTOR
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	MTOR
NIFEDIPINE	ChEMBL	Phase 4 (approved)	MTOR
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	MTOR
PACLITAXEL	ChEMBL	Phase 4 (approved)	MTOR
PANCURONIUM	ChEMBL	Phase 4 (approved)	MTOR
PAROXETINE	ChEMBL	Phase 4 (approved)	MTOR
PENTAMIDINE ISETHIONATE	ChEMBL	Phase 4 (approved)	MTOR
PERPHENAZINE	ChEMBL	Phase 4 (approved)	MTOR
PIMOZIDE	ChEMBL	Phase 4 (approved)	MTOR
PRAZOSIN	ChEMBL	Phase 4 (approved)	MTOR
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	MTOR
PROMAZINE	ChEMBL	Phase 4 (approved)	MTOR
PROMETHAZINE	ChEMBL	Phase 4 (approved)	MTOR
PROPAFENONE	ChEMBL	Phase 4 (approved)	MTOR
QUINACRINE	ChEMBL	Phase 4 (approved)	MTOR
RALOXIFENE	ChEMBL	Phase 4 (approved)	MTOR
SALMETEROL XINAFOATE	ChEMBL	Phase 4 (approved)	MTOR
SERTRALINE	ChEMBL	Phase 4 (approved)	MTOR
SIROLIMUS	ChEMBL	Phase 4 (approved)	MTOR
TACROLIMUS	ChEMBL	Phase 4 (approved)	MTOR
TAMOXIFEN	ChEMBL	Phase 4 (approved)	MTOR
TEMSIROLIMUS	ChEMBL	Phase 4 (approved)	MTOR
TERFENADINE	ChEMBL	Phase 4 (approved)	MTOR
TETRABENAZINE	ChEMBL	Phase 4 (approved)	MTOR
THIORIDAZINE	ChEMBL	Phase 4 (approved)	MTOR
TRIAMTERENE	ChEMBL	Phase 4 (approved)	MTOR
TRIFLUOPERAZINE	ChEMBL	Phase 4 (approved)	MTOR
TRIFLUPERIDOL	ChEMBL	Phase 4 (approved)	MTOR
TRIFLUPROMAZINE	ChEMBL	Phase 4 (approved)	MTOR
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	MTOR
BENSERAZIDE	ChEMBL	Phase 3	MTOR
BUPARLISIB	ChEMBL	Phase 3	MTOR
CERALASERTIB	ChEMBL	Phase 3	MTOR
CORTICOSTERONE	ChEMBL	Phase 3	MTOR
DACTOLISIB	ChEMBL	Phase 3	MTOR
EBSELEN	ChEMBL	Phase 3	MTOR
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	MTOR
FENRETINIDE	ChEMBL	Phase 3	MTOR
FLUPENTIXOL	ChEMBL	Phase 3	MTOR
GEDATOLISIB	ChEMBL	Phase 3	MTOR
GOSSYPOL	ChEMBL	Phase 3	MTOR
IDAZOXAN	ChEMBL	Phase 3	MTOR
LERCANIDIPINE	ChEMBL	Phase 3	MTOR
NITRENDIPINE	ChEMBL	Phase 3	MTOR
OXITRIPTAN	ChEMBL	Phase 3	MTOR
RESVERATROL	ChEMBL	Phase 3	MTOR
SEMAXANIB	ChEMBL	Phase 3	MTOR