Emricasan

Identification

Name
Emricasan
Accession Number
DB05408
Type
Small Molecule
Groups
Investigational
Description

Emricasan is the first caspase inhibitor tested in human which has received orphan drug status by FDA. It is developed by Pfizer and made in such a way that it protects liver cells from excessive apoptosis.

Structure
Thumb
Synonyms
Not Available
External IDs
IDN 6556 / IDN-6556 / PF-3491390
Categories
UNII
P0GMS9N47Q
CAS number
Not Available
Weight
Average: 569.51
Monoisotopic: 569.178512873
Chemical Formula
C26H27F4N3O7
InChI Key
SCVHJVCATBPIHN-SJCJKPOMSA-N
InChI
InChI=1S/C26H27F4N3O7/c1-12(31-24(38)25(39)32-16-8-6-5-7-13(16)26(2,3)4)23(37)33-17(10-19(35)36)18(34)11-40-22-20(29)14(27)9-15(28)21(22)30/h5-9,12,17H,10-11H2,1-4H3,(H,31,38)(H,32,39)(H,33,37)(H,35,36)/t12-,17-/m0/s1
IUPAC Name
(3S)-3-[(2S)-2-{[(2-tert-butylphenyl)carbamoyl]formamido}propanamido]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid
SMILES
C[[email protected]](NC(=O)C(=O)NC1=CC=CC=C1C(C)(C)C)C(=O)N[[email protected]@H](CC(O)=O)C(=O)COC1=C(F)C(F)=CC(F)=C1F

Pharmacology

Indication

Investigated for use/treatment in hepatitis (viral, C), liver disease, and transplantation (organ or tissue).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

IDN-6556 significantly improves markers of liver damage in patients infected with the Hepatitis C virus (HCV), an infection that affects up to 170m patients worldwide. IDN-6556 represents a new class of drugs that protect the liver from inflammation and cellular damage induced by viral infections and other causes. Various studies have also shown that it significantly lowers aminotransferase activity in HCV patients and appeared to be well tolerated.

TargetActionsOrganism
UCaspase-1Not AvailableHuman
UCaspase-3Not AvailableHuman
UCaspase-7Not 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
  1. Pockros PJ, Schiff ER, Shiffman ML, McHutchison JG, Gish RG, Afdhal NH, Makhviladze M, Huyghe M, Hecht D, Oltersdorf T, Shapiro DA: Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):324-9. [PubMed:17654603]
External Links
PubChem Compound
12000240
PubChem Substance
347827726
ChemSpider
10172707
ChEMBL
CHEMBL197672

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentDigestive System Diseases / Hepatic Impairment / Liver Diseases1
1CompletedTreatmentImpaired Renal Function / Kidney Diseases1
1, 2CompletedTreatmentDiabetes Mellitus (DM)1
2Active Not RecruitingTreatmentFibrosis, Liver / Hepatic Cirrhosis / Hepatic Fibrosis / Liver Cirrhosis1
2Active Not RecruitingTreatmentFibrosis / Liver Diseases / Non-Alcoholic Steatohepatitis1
2CompletedTreatmentCholestasis / Hepatitis / Hepatocellular,Carcinoma / Transplantation, Liver1
2CompletedTreatmentHepatic Cirrhosis / Liver Cirrhosis1
2CompletedTreatmentHepatic Cirrhosis / Liver Cirrhosis / Portal Hypertension1
2CompletedTreatmentHepatitis C, Chronic1
2CompletedTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD) / Nonalcoholic Steatohepatitis1
2RecruitingTreatmentCirrhosis, Decompensated1
2RecruitingTreatmentLiver Cirrhosis / Non-Alcoholic Steatohepatitis / Portal Hypertension1
2TerminatedTreatmentAcute Alcoholic Hepatitis / Acute on Chronic Hepatic Failure / Fulminant Hepatic Failure / Liver Cirrhosis1
2TerminatedTreatmentAlcoholic Hepatitis (AH)1

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 Solubility0.00213 mg/mLALOGPS
logP3.48ALOGPS
logP3.42ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)3.51ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area150.9 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity132.39 m3·mol-1ChemAxon
Polarizability51.13 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Hybrid peptides
Direct Parent
Hybrid peptides
Alternative Parents
N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Alanine and derivatives / Beta amino acids and derivatives / Phenylpropanes / Anilides / Phenoxy compounds / Phenol ethers / N-arylamides / Gamma-keto acids and derivatives
show 12 more
Substituents
Hybrid peptide / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Alanine or derivatives / Beta amino acid or derivatives / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Anilide / Phenylpropane / Phenoxy compound
show 30 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Cle...
Gene Name
CASP1
Uniprot ID
P29466
Uniprot Name
Caspase-1
Molecular Weight
45158.215 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phospholipase a2 activator activity
Specific Function
Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' ...
Gene Name
CASP3
Uniprot ID
P42574
Uniprot Name
Caspase-3
Molecular Weight
31607.58 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Cysteine-type peptidase activity
Specific Function
Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribos...
Gene Name
CASP7
Uniprot ID
P55210
Uniprot Name
Caspase-7
Molecular Weight
34276.48 Da

Drug created on November 18, 2007 11:24 / Updated on December 01, 2017 15:35