Identification

Name
FM-VP4
Accession Number
DB05449
Type
Small Molecule
Groups
Investigational
Description

FM-VP4, is a novel hydrophilic phytostanol analogue representing a new class in cholesterol-lowering drugs called cholesterol absorption inhibitors. FM-VP4 has been shown to inhibit cholesterol absorption and to lower plasma LDL-cholesterol and total cholesterol in a broad range of animal species. Additional experiments suggest that FM-VP4 can reduce plasma LDL cholesterol levels and triglyceride levels, reduce weight gain and exert a anti-atherosclerosis effect

Synonyms
Not Available
International/Other Brands
Uknown
Categories
Not Available
UNII
Not Available
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Investigated for use/treatment in hyperlipidemia and cancer/tumors (unspecified).

Monotherapy is recommended for people with marginally high LDL-cholesterol or who cannot be prescribed statins due to drug interactions and safety concerns. Combination Therapy is recommended if statin therapy alone is either insufficient to achieve the guidelines set by the NCEP or there is concern over side effects as Statin doses can be lowered in combination treatment without losing efficacy.

Pharmacodynamics

FM VP4 is thought to bind competitively with cholesterol to MDR1 resulting in a synergistic decrease in cholesterol accumlation. Others have suggested that FM VP4 may act by inhibiting a transporter that mediates intestinal absorption of cholesterol.

Mechanism of action

FM VP4 is thought to bind competitively with cholesterol to MDR1 resulting in a synergistic decrease in cholesterol accumlation. Others have suggested that FM VP4 may act by inhibiting a transporter that mediates intestinal absorption of cholesterol. One study indicates that FM-VP4 inhibits cholesterol accumulation within IEC-6 cells and is most effective at equimolar concentrations with cholesterol, further suggesting that the action of FM-VP4 is likely at the cell surface and not elicited intracellularly.

TargetActionsOrganism
UMultidrug resistance protein 1Not 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

Clinical trials have indicated that the drug is well-tolerated.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Thornton SJ, Warburton C, Wasan KM, Kozlowski P: Treatment with a cholesterol absorption inhibitor (FM-VP4) reduces body mass and adipose accumulation in developing and pre-obese mice. Drug Dev Ind Pharm. 2007 Oct;33(10):1058-69. [PubMed:17963113]
  2. Burnett JR, Huff MW: Cholesterol absorption inhibitors as a therapeutic option for hypercholesterolaemia. Expert Opin Investig Drugs. 2006 Nov;15(11):1337-51. [PubMed:17040195]
  3. Looije NA, Risovic V, Stewart DJ, Debeyer D, Kutney J, Wasan KM: Disodium Ascorbyl Phytostanyl Phosphates (FM-VP4) reduces plasma cholesterol concentration, body weight and abdominal fat gain within a dietary-induced obese mouse model. J Pharm Pharm Sci. 2005 Aug 24;8(3):400-8. [PubMed:16401390]
  4. Jia X, Ebine N, Wang Y, Awad AB, Jones PJ: Effects of different phytosterol analogs on colonic mucosal cell proliferation in hamsters. J Nutr Biochem. 2006 Jun;17(6):396-401. Epub 2005 Sep 26. [PubMed:16243508]
  5. Ebine N, Jia X, Demonty I, Wang Y, Jones PJ: Effects of a water-soluble phytostanol ester on plasma cholesterol levels and red blood cell fragility in hamsters. Lipids. 2005 Feb;40(2):175-80. [PubMed:15884766]
  6. Ng AW, Lukic T, Pritchard PH, Wasan KM: Development and characterization of liposomal disodium ascorbyl phytostanyl phosphates (FM-VP4). Drug Dev Ind Pharm. 2004 Aug;30(7):739-58. [PubMed:15491052]
  7. Wasan KM, Choo E, Sivak O, Wallis S, Letchford K, Burt HM, Stewart DJ, Lukic T: Determining the critical micelle concentration of a novel lipid-lowering agent, disodium ascorbyl phytostanyl phosphate (FM-VP4), using a fluorescence depolarization procedure. Drug Dev Ind Pharm. 2004 Aug;30(7):725-30. [PubMed:15491050]
  8. Burnett JR: FM-VP4 Forbes Medi-Tech. Curr Opin Investig Drugs. 2003 Sep;4(9):1120-5. [PubMed:14582458]
  9. Ng AW, Lukic T, Pritchard PH, Wasan KM: Development of novel water-soluble phytostanol analogs: disodium ascorbyl phytostanyl phosphates (FM-VP4): preclinical pharmacology, pharmacokinetics and toxicology. Cardiovasc Drug Rev. 2003 Fall;21(3):151-68. [PubMed:12931251]
  10. Wasan KM, Yau E, Boulanger KD, Ramswamy M, Pritchard PH: Effects of disodium ascorbyl phytostanol phosphates (FM-VP4) on cholesterol accumulation within rat intestinal cells. AAPS PharmSci. 2003;5(1):E6. [PubMed:12713278]
  11. Lukic T, Wasan KM, Zamfir D, Moghadasian MH, Pritchard PH: Disodium ascorbyl phytostanyl phosphate reduces plasma cholesterol concentrations and atherosclerotic lesion formation in apolipoprotein E-deficient mice. Metabolism. 2003 Apr;52(4):425-31. [PubMed:12701053]
  12. Wasan KM, Zamfir C, Pritchard PH, Pederson RA: Influence of phytostanol phosphoryl ascorbate (FM-VP4) on insulin resistance, hyperglycemia, plasma lipid levels, and gastrointestinal absorption of exogenous cholesterol in Zucker (fa/fa) fatty and lean rats. J Pharm Sci. 2003 Feb;92(2):281-8. [PubMed:12532378]
  13. Ramaswamy M, Yau E, Wasan KM, Boulanger KD, Li M, Pritchard PH: Influence of phytostanol phosphoryl ascorbate, FM-VP4, on pancreatic lipase activity and cholesterol accumulation within Caco-2 cells. J Pharm Pharm Sci. 2002 Jan-Apr;5(1):29-38. [PubMed:12042117]
  14. Wasan KM, Najafi S, Peteherych KD, Pritchard PH: Effects of a novel hydrophilic phytostanol analog on plasma lipid concentrations in gerbils. J Pharm Sci. 2001 Nov;90(11):1795-9. [PubMed:11745737]
  15. Wasan KM, Najafi S, Wong J, Kwong M, Pritchard PH: Assessing plasma lipid levels, body weight, and hepatic and renal toxicity following chronic oral administration of a water soluble phytostanol compound, FM-VP4, to gerbils. J Pharm Pharm Sci. 2001 Sep-Dec;4(3):228-34. [PubMed:11737988]
  16. Wasan KM, Peteherych KD, Najafi S, Zamfir C, Pritchard PH: Assessing the plasma pharmacokinetics, tissue distribution, excretion and effects on cholesterol pharmacokinetics of a novel hydrophilic compound, FM-VP4, following administration to rats. J Pharm Pharm Sci. 2001 Sep-Dec;4(3):207-16. [PubMed:11737986]
External Links
PubChem Substance
347910145

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHigh Cholesterol1

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
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da

Drug created on November 18, 2007 11:25 / Updated on November 02, 2018 06:10