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Accession NumberDB04875
TypeSmall Molecule
DescriptionPralnacasan is an orally bioavailable pro-drug of a potent, non-peptide inhibitor of interleukin-1beta converting enzyme (ICE).
HMR 3480
External IDs VX-740
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number192755-52-5
WeightAverage: 523.5378
Monoisotopic: 523.206698307
Chemical FormulaC26H29N5O7
CCO[C@@H]1OC(=O)C[C@@H]1NC(=O)[C@@H]1CCCN2N1C(=O)[[email protected]](CCC2=O)NC(=O)C1=NC=CC2=CC=CC=C12
IndicationFor the treatment of rheumatoid arthritis (RA).
Structured Indications Not Available
PharmacodynamicsPralnacasan is a potent, non-peptide inhibitor of interleukin-1beta converting enzyme (ICE). Pralnacasan is an oral, anti-cytokine drug candidate licensed for development by Aventis Pharma from Vertex Pharmaceuticals. In November 2003, Aventis and Vertex Pharmaceuticals announced that they had voluntarily suspended the phase II clinical trials of pralnacasan due to results from an animal toxicity study that demonstrated liver abnormalities after a nine-month exposure to pralnacasan at high doses. While no similar liver toxicity has been seen to date in human trials, the companies will evaluate the animal toxicity results before proceeding with the phase II clinical program.
Mechanism of actionPralnacasan inhibits interleukin-1beta converting enzyme (ICE), an enzyme that regulates the production of IL-1 and IFN gamma - intercellular mediators that initiate and sustain the process of inflammation. Inhibiting ICE may be an effective strategy for curtailing damaging inflammatory processes common to a number of acute and chronic conditions, such as rheumatoid arthritis (RA) and osteoarthritis.
TargetKindPharmacological actionActionsOrganismUniProt ID
Caspase-1ProteinunknownNot AvailableHumanP29466 details
Related Articles
AbsorptionOrally bioavailable
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Drug Interactions Not Available
Food InteractionsNot Available
Synthesis ReferenceNot Available
General References
  1. Ross J, Brough D, Gibson RM, Loddick SA, Rothwell NJ: A selective, non-peptide caspase-1 inhibitor, VRT-018858, markedly reduces brain damage induced by transient ischemia in the rat. Neuropharmacology. 2007 Oct;53(5):638-42. Epub 2007 Aug 10. [PubMed:17845807 ]
  2. Loher F, Bauer C, Landauer N, Schmall K, Siegmund B, Lehr HA, Dauer M, Schoenharting M, Endres S, Eigler A: The interleukin-1 beta-converting enzyme inhibitor pralnacasan reduces dextran sulfate sodium-induced murine colitis and T helper 1 T-cell activation. J Pharmacol Exp Ther. 2004 Feb;308(2):583-90. Epub 2003 Nov 10. [PubMed:14610233 ]
  3. Rudolphi K, Gerwin N, Verzijl N, van der Kraan P, van den Berg W: Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage. 2003 Oct;11(10):738-46. [PubMed:13129693 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials Not Available
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Experimental PropertiesNot Available
Predicted Properties
Water Solubility0.387 mg/mLALOGPS
pKa (Strongest Acidic)12.26ChemAxon
pKa (Strongest Basic)1.49ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area147.24 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity131.03 m3·mol-1ChemAxon
Polarizability52.27 Å3ChemAxon
Number of Rings5ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Human Intestinal Absorption+0.9821
Blood Brain Barrier-0.8386
Caco-2 permeable-0.7237
P-glycoprotein substrateSubstrate0.7204
P-glycoprotein inhibitor IInhibitor0.7443
P-glycoprotein inhibitor IINon-inhibitor0.9365
Renal organic cation transporterNon-inhibitor0.7706
CYP450 2C9 substrateNon-substrate0.834
CYP450 2D6 substrateNon-substrate0.835
CYP450 3A4 substrateSubstrate0.6186
CYP450 1A2 substrateNon-inhibitor0.8814
CYP450 2C9 inhibitorNon-inhibitor0.7453
CYP450 2D6 inhibitorNon-inhibitor0.8095
CYP450 2C19 inhibitorNon-inhibitor0.7977
CYP450 3A4 inhibitorNon-inhibitor0.5643
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5861
Ames testNon AMES toxic0.5288
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4106 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9197
hERG inhibition (predictor II)Non-inhibitor0.5157
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Mass Spec (NIST)Not Available
SpectraNot Available
DescriptionThis compound belongs to the class of chemical entities known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentDipeptides
Alternative Parents
  • Alpha-dipeptide
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Alpha-amino acid or derivatives
  • Isoquinoline
  • Pyridine carboxylic acid or derivatives
  • 2-heteroaryl carboxamide
  • 1,2-diazepane
  • Diazepane
  • Diacylhydrazine
  • 1,2-diazinane
  • Gamma butyrolactone
  • Pyridazine
  • Benzenoid
  • Pyridine
  • Heteroaromatic compound
  • Oxolane
  • Secondary carboxylic acid amide
  • Lactone
  • Carboxamide group
  • Carboxylic acid ester
  • Carboxylic acid hydrazide
  • Acetal
  • Organoheterocyclic compound
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Oxacycle
  • Organooxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available


Pharmacological action
General Function:
Endopeptidase activity
Specific Function:
Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.
Gene Name:
Uniprot ID:
Molecular Weight:
45158.215 Da
  1. Ross J, Brough D, Gibson RM, Loddick SA, Rothwell NJ: A selective, non-peptide caspase-1 inhibitor, VRT-018858, markedly reduces brain damage induced by transient ischemia in the rat. Neuropharmacology. 2007 Oct;53(5):638-42. Epub 2007 Aug 10. [PubMed:17845807 ]
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Drug created on October 20, 2007 05:27 / Updated on August 17, 2016 12:24