This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Ridaforolimus
Accession Number
DB06233
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • Deforolimus
External IDs
AP 23573 / AP-23573 / AP23573 / MK-8669
Categories
UNII
48Z35KB15K
CAS number
572924-54-0
Weight
Average: 990.222
Monoisotopic: 989.562943387
Chemical Formula
C53H84NO14P
InChI Key
BUROJSBIWGDYCN-GAUTUEMISA-N
InChI
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
IUPAC Name
(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.0^{4,9}]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl dimethylphosphinate
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)N3CCCC[C@H]3C(=O)O2)OC)CC[C@H]1OP(C)(C)=O

Pharmacology

Indication

Investigated for use/treatment in solid tumors, sarcoma, cancer/tumors (unspecified), endometrial cancer, prostate cancer, and bone metastases.

Pharmacodynamics
Not Available
Mechanism of action

Deforolimus inhibits the mammalian target of rapamycin (mTOR), a serine kinase of the phosphatidylinositol-3-kinase (PI3K) family that regulates protein synthesis, affecting cell growth and proliferation. mTOR is a downstream effector of the phosphatidylinositol 3-kinase/Akt and nutrient-sensing pathways which cancer cells need to proliferate.

TargetActionsOrganism
USerine/threonine-protein kinase mTORNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Ridaforolimus.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ridaforolimus.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Ridaforolimus.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Ridaforolimus.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Ridaforolimus.
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Ridaforolimus.
AmcinonideThe metabolism of Amcinonide can be decreased when combined with Ridaforolimus.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Ridaforolimus.
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Ridaforolimus.
AtorvastatinThe risk or severity of rhabdomyolysis can be increased when Ridaforolimus is combined with Atorvastatin.
Food Interactions
Not Available

References

General References
  1. Mita MM, Mita AC, Chu QS, Rowinsky EK, Fetterly GJ, Goldston M, Patnaik A, Mathews L, Ricart AD, Mays T, Knowles H, Rivera VM, Kreisberg J, Bedrosian CL, Tolcher AW: Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies. J Clin Oncol. 2008 Jan 20;26(3):361-7. doi: 10.1200/JCO.2007.12.0345. [PubMed:18202410]
  2. Rizzieri DA, Feldman E, Dipersio JF, Gabrail N, Stock W, Strair R, Rivera VM, Albitar M, Bedrosian CL, Giles FJ: A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2008 May 1;14(9):2756-62. doi: 10.1158/1078-0432.CCR-07-1372. [PubMed:18451242]
External Links
KEGG Compound
C15183
ChemSpider
24597928
ChEBI
79700
ChEMBL
CHEMBL2103839
Wikipedia
Deforolimus
ATC Codes
L01XE19 — Ridaforolimus

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancer of the Ovary / Endometrial Cancers1
1CompletedTreatmentCancer, Advanced2
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentCancers1
1CompletedTreatmentCancers / Sarcomas1
1CompletedTreatmentGlioblastomas / Gliosarcoma / Malignant Gliomas1
1CompletedTreatmentHealthy Volunteers / Hepatic Insufficiency1
1CompletedTreatmentMalignant Lymphomas / Multiple Myeloma (MM) / Tumors2
1CompletedTreatmentMalignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMetastatic or Locally Advanced Cancer1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentRelapsed or Refractory Advanced Cancer1
1CompletedTreatmentTumors, Solid3
1TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1TerminatedTreatmentNeoplasms Malignant1
1TerminatedTreatmentTumors, Solid1
1WithdrawnTreatmentSoft Tissue Sarcoma (STS)1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCancer, Breast / Neoplasms, Breast1
2CompletedTreatmentEndometrial Cancers3
2CompletedTreatmentLeiomyosarcomas / Liposarcoma / Metastases / Sarcoma, Osteogenic / Soft Tissue Sarcoma (STS)1
2CompletedTreatmentLeukemias / Malignancies, Hematologic / Malignant Lymphomas / Myelodysplastic Syndromes / Myeloid Metaplasia1
2CompletedTreatmentProstate Cancer2
2CompletedTreatmentSarcomas1
2TerminatedTreatmentAdvanced Cancers1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentNeoplasms, Breast1
3CompletedTreatmentMetastatic Bone Sarcomas / Metastatic Soft-Tissue Sarcomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000805 mg/mLALOGPS
logP4.84ALOGPS
logP7.25ChemAxon
logS-6.1ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area201.5 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity267.98 m3·mol-1ChemAxon
Polarizability107.25 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as macrolide lactams. These are cyclic polyketides containing both a cyclic amide and a cyclic ester group.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolide lactams
Sub Class
Not Available
Direct Parent
Macrolide lactams
Alternative Parents
Alpha amino acid esters / Macrolides and analogues / Piperidines / Oxanes / Tertiary carboxylic acid amides / Secondary alcohols / Carboxylic acid esters / Cyclic ketones / Hemiacetals / Lactams
show 10 more
Substituents
Macrolide lactam / Alpha-amino acid ester / Macrolide / Alpha-amino acid or derivatives / Piperidine / Oxane / Tertiary carboxylic acid amide / Carboxamide group / Carboxylic acid ester / Hemiacetal
show 24 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
lactam, macrolide (CHEBI:79700)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tfiiic-class transcription factor binding
Specific Function
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly...
Gene Name
MTOR
Uniprot ID
P42345
Uniprot Name
Serine/threonine-protein kinase mTOR
Molecular Weight
288889.05 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. [PubMed:11020135]

Drug created on March 19, 2008 10:18 / Updated on September 13, 2018 15:54