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Identification
NameCrofelemer
Accession NumberDB04941
TypeSmall Molecule
GroupsApproved
DescriptionCrofelemer, previously known as the investigational drug SP-303, is a novel proanthocyanidin purified from the bark latex of the Amazonian Croton tree Croton lechleri. It is marketed under the brand name Fulyzaq and indicated for the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.
Structure
Thumb
Synonyms
Provir
SP-303
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FulyzaqTablet, coated125 mg/1OralSalix Pharmaceuticals, Inc.2012-12-31Not applicableUs
MytesiTablet, coated125 mg/1OralNapo Pharmaceuticals, Inc.2016-04-12Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIPY79D6C8RX
CAS number148465-45-6
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Pharmacology
IndicationFor the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.
Structured Indications
PharmacodynamicsCrofelemer is an inhibitor of secretory diarrhea via inhibition of the CFTR chloride transporter. Crofelemer is not an antimicrobial, and therefore does not drive the emergence of resistance; it does not inhibit motility, and therefore does not cause constipation or rebound diarrhea; and it is not systemically absorbed, reducing the potential for adverse drug interactions and toxicity.
Mechanism of actionCrofelemer is an inhibitor of the cystic fibrosis transmembrane regulator chloride channel (CFTR), as evidenced by its activity on cell cultures, single cell patch clamps, single CFTR channels, and elaboration of mouse intestinal fluid secretion. Crofelemer also inhibits calcium activated chloride channels (CaCC), which in combination with CFTR, are expressed on the luminal side of intestinal cells. Crofelemer inhibition of both of these channels prevents water loss from diarrhea by inhibiting chloride secretion.
TargetKindPharmacological actionActionsOrganismUniProt ID
Cystic fibrosis transmembrane conductance regulatorProteinyes
antagonist
HumanP13569 details
Anoctamin-1Proteinyes
antagonist
HumanQ5XXA6 details
Related Articles
AbsorptionThe absorption of crofelemer is minimal and crofelemer concentrations in plasma are below the level of quantitation (50 ng/mL).
Volume of distribution

Since crofelemer is not significantly absorbed, volume of distribution was not quantified.

Protein bindingSince crofelemer is not significantly absorbed, protein binding was not quantified.
Metabolism

Since crofelemer is not significantly absorbed, no metabolites have been identified.

Route of eliminationSince crofelemer is not significantly absorbed, the route of elimination has not been identified.
Half lifeSince crofelemer is not significantly absorbed, the half life was not determined.
Clearance

Since crofelemer is not significantly absorbed, clearance was not determined.

ToxicityThe most common adverse effects are cough, flatulence, upper respiratory tract infection, bronchitis, and increased bilirubin.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Crutchley RD, Miller J, Garey KW: Crofelemer, a novel agent for treatment of secretory diarrhea. Ann Pharmacother. 2010 May;44(5):878-84. doi: 10.1345/aph.1M658. Epub 2010 Apr 13. [PubMed:20388859 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (357 KB)
MSDSDownload (566 KB)
ADMET
Predicted ADMET featuresNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, coatedOral125 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7,341,744 No2000-11-142020-11-14Us
US7323195 No1998-06-072018-06-07Us
US7341744 No1998-06-162018-06-16Us
US8574634 No1998-01-112018-01-11Us
US8962680 No2011-10-312031-10-31Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Taxonomy
ClassificationNot classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Pdz domain binding
Specific Function:
Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
Gene Name:
CFTR
Uniprot ID:
P13569
Molecular Weight:
168139.895 Da
References
  1. Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. [PubMed:19808995 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Voltage-gated chloride channel activity
Specific Function:
Calcium-activated chloride channel (CaCC) which plays a role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays a...
Gene Name:
ANO1
Uniprot ID:
Q5XXA6
Molecular Weight:
114077.215 Da
References
  1. Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. [PubMed:19808995 ]
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Drug created on October 21, 2007 16:23 / Updated on December 05, 2016 02:44