Perifosine

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

Identification

Name
Perifosine
Accession Number
DB06641
Type
Small Molecule
Groups
Investigational
Description

Perifosine is a novel alkylphospholipid with antiproliferative properties attributed to protein kinase B inhibition.

Structure
Thumb
Synonyms
Not Available
External IDs
KRX-0401 / NSC-639966
Categories
UNII
2GWV496552
CAS number
157716-52-4
Weight
Average: 461.668
Monoisotopic: 461.363396156
Chemical Formula
C25H52NO4P
InChI Key
SZFPYBIJACMNJV-UHFFFAOYSA-N
InChI
InChI=1S/C25H52NO4P/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-24-29-31(27,28)30-25-20-22-26(2,3)23-21-25/h25H,4-24H2,1-3H3
IUPAC Name
1,1-dimethyl-4-{[(octadecyloxy)phosphinato]oxy}piperidin-1-ium
SMILES
CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1

Pharmacology

Indication

Investigated for use/treatment in solid tumors, multiple myeloma, leukemia (unspecified), lung cancer, and brain cancer.

Pharmacodynamics
Not Available
Mechanism of action

Targeting cellular membranes, perifosine modulates membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis.

TargetActionsOrganism
URAC-alpha serine/threonine-protein kinaseNot AvailableHuman
UMitogen-activated protein kinase 1Not AvailableHuman
UProtein kinase C alpha typeNot 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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
ChemSpider
130628
BindingDB
50431630
ChEBI
67272
ChEMBL
CHEMBL372764
Wikipedia
Perifosine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAccelerated Phase Chronic Myelogenous Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Acute Promyelocytic Leukemia (M3) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Blastic Phase Chronic Myelogenous Leukemia / Myelodysplastic/Myeloproliferative Neoplasms / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Relapsing Chronic Myelogenous Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / T-cell Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Myeloid Leukemia1
1CompletedTreatmentCancer of the Ovary1
1CompletedTreatmentGIST / Renal Cancers1
1CompletedTreatmentLeukemias / Malignant Lymphomas / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMalignancies1
1CompletedTreatmentMalignant Neoplasm of Colon1
1CompletedTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentNeoplasms3
1CompletedTreatmentPediatric Solid Tumors1
1CompletedTreatmentRenal Cancers / Tumors1
1CompletedTreatmentTumors, Solid1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentMultiple Myeloma (MM) / Multiple Myeloma in Relapse1
1, 2TerminatedTreatmentAdult Anaplastic Astrocytoma / Adult Anaplastic Oligodendroglioma / Adult Diffuse Astrocytoma / Adult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Adult Mixed Glioma / Adult Oligodendroglioma / Recurrent Adult Brain Neoplasm1
2Active Not RecruitingTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligodendroglioma (AO) / Glioblastomas / Mixed Gliomas / Recurrent Brain Tumors1
2Active Not RecruitingTreatmentBrain Cancer / CNS / Malignancies / Malignant Gliomas1
2CompletedTreatmentAlveolar Soft Part Sarcomas / Chondrosarcomas / Extra Skeletal Myxoid Chondrosarcomas1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2CompletedTreatmentEndometrial Cancers / Sarcomas1
2CompletedTreatmentGastrointestinal Stromal Tumors1
2CompletedTreatmentLeukemias1
2CompletedTreatmentMalignant Lymphomas / Tumors1
2CompletedTreatmentMalignant Neoplasm of Colon1
2CompletedTreatmentMalignant Neoplasm of Pancreas2
2CompletedTreatmentMelanoma (Skin)1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRecurrent Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2CompletedTreatmentRenal Cancers1
2CompletedTreatmentRenal Cell Adenocarcinoma1
2CompletedTreatmentWaldenström's Macroglobulinemia (WM)2
2TerminatedTreatmentAdenocarcinoma of the Prostate / Recurrent Prostate Cancer / Stage IIB Prostate Cancer / Stage III Prostate Cancer / Stage IV Prostate Cancer1
2TerminatedTreatmentHead and Neck Carcinoma1
3CompletedTreatmentColorectal Cancers1
3TerminatedTreatmentMultiple Myeloma (MM)1
Not AvailableCompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Breast Cancer (MBC) / Sarcomas / Tumors, Solid1

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 Solubility0.000101 mg/mLALOGPS
logP3.82ALOGPS
logP3.15ChemAxon
logS-6.7ALOGPS
pKa (Strongest Acidic)1.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area58.59 Å2ChemAxon
Rotatable Bond Count20ChemAxon
Refractivity142.15 m3·mol-1ChemAxon
Polarizability58.14 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as dialkyl phosphates. These are organic compounds containing a phosphate group that is linked to exactly two alkyl chain.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphoric acids and derivatives
Sub Class
Phosphate esters
Direct Parent
Dialkyl phosphates
Alternative Parents
Piperidines / Tetraalkylammonium salts / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives / Amines
Substituents
Dialkyl phosphate / Piperidine / Quaternary ammonium salt / Tetraalkylammonium salt / Organoheterocyclic compound / Azacycle / Amine / Organic salt / Organopnictogen compound / Organic oxygen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
ammonium betaine, phospholipid (CHEBI:67272)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, ...
Gene Name
AKT1
Uniprot ID
P31749
Uniprot Name
RAC-alpha serine/threonine-protein kinase
Molecular Weight
55686.035 Da
References
  1. Shome D, Trent J, Espandar L, Hatef E, Araujo DM, Song CD, Kim SK, Esmaeli B: Ulcerative keratitis in gastrointestinal stromal tumor patients treated with perifosine. Ophthalmology. 2008 Mar;115(3):483-7. doi: 10.1016/j.ophtha.2007.11.016. Epub 2008 Jan 16. [PubMed:18201764]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
Gene Name
MAPK1
Uniprot ID
P28482
Uniprot Name
Mitogen-activated protein kinase 1
Molecular Weight
41389.265 Da
References
  1. Knowling M, Blackstein M, Tozer R, Bramwell V, Dancey J, Dore N, Matthews S, Eisenhauer E: A phase II study of perifosine (D-21226) in patients with previously untreated metastatic or locally advanced soft tissue sarcoma: A National Cancer Institute of Canada Clinical Trials Group trial. Invest New Drugs. 2006 Sep;24(5):435-9. [PubMed:16528479]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differenti...
Gene Name
PRKCA
Uniprot ID
P17252
Uniprot Name
Protein kinase C alpha type
Molecular Weight
76749.445 Da
References
  1. Knowling M, Blackstein M, Tozer R, Bramwell V, Dancey J, Dore N, Matthews S, Eisenhauer E: A phase II study of perifosine (D-21226) in patients with previously untreated metastatic or locally advanced soft tissue sarcoma: A National Cancer Institute of Canada Clinical Trials Group trial. Invest New Drugs. 2006 Sep;24(5):435-9. [PubMed:16528479]

Drug created on March 19, 2008 10:43 / Updated on November 02, 2018 06:18