Ciluprevir
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Ciluprevir
- DrugBank Accession Number
- DB05868
- Background
The compound, named BILN 2061, is an orally active inhibitor of the HCV NS3 protease and the first member of this new drug class to be tested in humans.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 774.925
Monoisotopic: 774.341083296 - Chemical Formula
- C40H50N6O8S
- Synonyms
- Ciluprevir
- External IDs
- BILN 2061
- BILN 2061 ZW
Pharmacology
- Indication
Investigated for use/treatment in hepatitis (viral, C).
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- Pharmacodynamics
Not Available
- Mechanism of action
A distinguishing feature of the BILN 2061 inhibitor series is the presence of C-terminal carboxylic acid functionality. This provides exquisite selectivity with respect to other proteases, a property not easily attained with more conventional classes of covalent, reversible serine protease inhibitors. BILN 2061 blocks NS3 protease-dependent polyprotein processing in HCV replicon-containing cells. It is orally bioavailable in various animal species.
Target Actions Organism AGenome polyprotein inhibitor- 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Cyclic peptides
- Alternative Parents
- Macrolactams / Alpha amino acids and derivatives / Quinolines and derivatives / Anisoles / Secondary alkylarylamines / Alkyl aryl ethers / 2,4-disubstituted thiazoles / Cyclopropanecarboxylic acids / Pyridines and derivatives / 2-amino-1,3-thiazoles show 15 more
- Substituents
- 1,3-thiazol-2-amine / 2,4-disubstituted 1,3-thiazole / Alkyl aryl ether / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Anisole / Aromatic heteropolycyclic compound / Azacycle show 31 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 75C8DU40T0
- CAS number
- 300832-84-2
- InChI Key
- PJZPDFUUXKKDNB-KNINVFKUSA-N
- InChI
- InChI=1S/C40H50N6O8S/c1-23(2)41-38-43-32(22-55-38)31-19-34(28-16-15-26(52-3)17-30(28)42-31)53-27-18-33-35(47)45-40(37(49)50)20-24(40)11-7-5-4-6-8-14-29(36(48)46(33)21-27)44-39(51)54-25-12-9-10-13-25/h7,11,15-17,19,22-25,27,29,33H,4-6,8-10,12-14,18,20-21H2,1-3H3,(H,41,43)(H,44,51)(H,45,47)(H,49,50)/b11-7-/t24-,27-,29+,33+,40-/m1/s1
- IUPAC Name
- (1S,4R,6S,7Z,14S,18R)-14-{[(cyclopentyloxy)carbonyl]amino}-18-[(7-methoxy-2-{2-[(propan-2-yl)amino]-1,3-thiazol-4-yl}quinolin-4-yl)oxy]-2,15-dioxo-3,16-diazatricyclo[14.3.0.0^{4,6}]nonadec-7-ene-4-carboxylic acid
- SMILES
- COC1=CC2=C(C=C1)C(O[C@H]1CN3C(=O)[C@H](CCCCC\C=C/[C@]4([H])C[C@@]4(C(O)=O)NC(=O)[C@]3([H])C1)NC(=O)OC1CCCC1)=CC(=N2)C1=CSC(NC(C)C)=N1
References
- General References
- Vanwolleghem T, Meuleman P, Libbrecht L, Roskams T, De Vos R, Leroux-Roels G: Ultra-rapid cardiotoxicity of the hepatitis C virus protease inhibitor BILN 2061 in the urokinase-type plasminogen activator mouse. Gastroenterology. 2007 Oct;133(4):1144-55. Epub 2007 Jul 10. [Article]
- External Links
- PubChem Compound
- 9853710
- PubChem Substance
- 175427047
- ChemSpider
- 8029420
- BindingDB
- 50142916
- ChEMBL
- CHEMBL297884
- ZINC
- ZINC000150339466
- Wikipedia
- Ciluprevir
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection / Cirrhosis of the Liver 1 somestatus stop reason just information to hide 1 Completed Treatment Healthy Volunteers (HV) 1 somestatus stop reason just information to hide 1, 2 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.00288 mg/mL ALOGPS logP 4.43 ALOGPS logP 5.4 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 3.73 Chemaxon pKa (Strongest Basic) 2.37 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 181.31 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 204.13 m3·mol-1 Chemaxon Polarizability 82.61 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.69 Blood Brain Barrier - 0.985 Caco-2 permeable - 0.6969 P-glycoprotein substrate Substrate 0.8509 P-glycoprotein inhibitor I Inhibitor 0.6345 P-glycoprotein inhibitor II Non-inhibitor 0.7165 Renal organic cation transporter Non-inhibitor 0.9204 CYP450 2C9 substrate Non-substrate 0.719 CYP450 2D6 substrate Non-substrate 0.7731 CYP450 3A4 substrate Substrate 0.7173 CYP450 1A2 substrate Non-inhibitor 0.7649 CYP450 2C9 inhibitor Non-inhibitor 0.5721 CYP450 2D6 inhibitor Non-inhibitor 0.8385 CYP450 2C19 inhibitor Non-inhibitor 0.5 CYP450 3A4 inhibitor Inhibitor 0.5355 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6419 Ames test Non AMES toxic 0.6693 Carcinogenicity Non-carcinogens 0.877 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6030 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9765 hERG inhibition (predictor II) Inhibitor 0.5447
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 271.82162 predictedDeepCCS 1.0 (2019) [M+H]+ 273.66763 predictedDeepCCS 1.0 (2019) [M+Na]+ 279.8743 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Mature core protein Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (PubMed:8533458). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (PubMed:9110985). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (PubMed:9524287). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (PubMed:9811706). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).
- Specific Function
- ATP binding
- Gene Name
- Not Available
- Uniprot ID
- P26664
- Uniprot Name
- Genome polyprotein
- Molecular Weight
- 327198.77 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at November 18, 2007 18:28 / Updated at October 29, 2024 17:59