Implitapide
Identification
- Generic Name
- Implitapide
- DrugBank Accession Number
- DB04852
- Background
Implitapide is a microsomal triglyceride transfer protein (MTP)-inhibitor.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 531.6872
Monoisotopic: 531.288577443 - Chemical Formula
- C35H37N3O2
- Synonyms
- Implitapide
- External IDs
- BAY-13-9952
Pharmacology
- Indication
For the treatment of atherosclerosis.
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- Pharmacodynamics
Implitapide is an inhibitor of microsomal triglyceride transfer protein (MTP), a key enzyme involved in the assembly and release of cholesterol and triglyceride from the liver and intestinal tract. It is being investigated for the treatment of atherosclerosis.
- Mechanism of action
MTP mediates triglyceride absorption and chylomicron secretion from the intestine and very-low-density lipoprotein (VLDL) secretion from the liver by linking lipid molecules with apolipoprotein B (apoB). Inhibition of MTP reduces the level of all apoB-containing lipoproteins, including LDL.
Target Actions Organism UMicrosomal triglyceride transfer protein large subunit Not Available Humans - 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 alpha carbolines. These are organic compounds containing a pyrido[2,3-b]indole core (which is a pyridine fused to an indole).
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Pyridoindoles
- Direct Parent
- Alpha carbolines
- Alternative Parents
- Phenylacetamides / N-alkylindoles / Pyrrolopyridines / Indoles / Methylpyridines / Substituted pyrroles / Heteroaromatic compounds / Secondary carboxylic acid amides / Azacyclic compounds / Primary alcohols show 5 more
- Substituents
- Alcohol / Alpha-carboline / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Heteroaromatic compound / Hydrocarbon derivative show 17 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q70OH404HR
- CAS number
- 177469-96-4
- InChI Key
- AMNXBQPRODZJQR-DITALETJSA-N
- InChI
- InChI=1S/C35H37N3O2/c1-23-19-24(2)36-34-32(23)29-17-8-9-18-31(29)38(34)21-25-11-10-16-28(20-25)33(27-14-6-7-15-27)35(40)37-30(22-39)26-12-4-3-5-13-26/h3-5,8-13,16-20,27,30,33,39H,6-7,14-15,21-22H2,1-2H3,(H,37,40)/t30-,33-/m0/s1
- IUPAC Name
- (2S)-2-cyclopentyl-2-[3-({2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl}methyl)phenyl]-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide
- SMILES
- CC1=NC2=C(C3=CC=CC=C3N2CC2=CC(=CC=C2)[C@H](C2CCCC2)C(=O)N[C@@H](CO)C2=CC=CC=C2)C(C)=C1
References
- General References
- Pahan K: Lipid-lowering drugs. Cell Mol Life Sci. 2006 May;63(10):1165-78. [Article]
- Iglesias P, Diez JJ: New drugs for the treatment of hypercholesterolaemia. Expert Opin Investig Drugs. 2003 Nov;12(11):1777-89. [Article]
- Shiomi M, Ito T: MTP inhibitor decreases plasma cholesterol levels in LDL receptor-deficient WHHL rabbits by lowering the VLDL secretion. Eur J Pharmacol. 2001 Nov 9;431(1):127-31. [Article]
- External Links
- PubChem Compound
- 5745206
- PubChem Substance
- 175426863
- ChemSpider
- 4676524
- ChEMBL
- CHEMBL2105804
- ZINC
- ZINC000059676426
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Terminated Treatment Hypertriglyceridemias 1 2 Terminated Treatment Primary Hypercholesterolemia 2
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 0.000202 mg/mL ALOGPS logP 6.43 ALOGPS logP 6.68 Chemaxon logS -6.4 ALOGPS pKa (Strongest Acidic) 13.2 Chemaxon pKa (Strongest Basic) 3.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 67.15 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 160.14 m3·mol-1 Chemaxon Polarizability 59.81 Å3 Chemaxon Number of Rings 6 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 + 0.9789 Blood Brain Barrier + 0.737 Caco-2 permeable - 0.7737 P-glycoprotein substrate Substrate 0.7286 P-glycoprotein inhibitor I Non-inhibitor 0.875 P-glycoprotein inhibitor II Non-inhibitor 0.6584 Renal organic cation transporter Non-inhibitor 0.7036 CYP450 2C9 substrate Non-substrate 0.7341 CYP450 2D6 substrate Non-substrate 0.732 CYP450 3A4 substrate Non-substrate 0.5165 CYP450 1A2 substrate Inhibitor 0.618 CYP450 2C9 inhibitor Non-inhibitor 0.6956 CYP450 2D6 inhibitor Non-inhibitor 0.8205 CYP450 2C19 inhibitor Non-inhibitor 0.7036 CYP450 3A4 inhibitor Non-inhibitor 0.8501 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5876 Ames test Non AMES toxic 0.7231 Carcinogenicity Non-carcinogens 0.917 Biodegradation Not ready biodegradable 0.8258 Rat acute toxicity 2.4158 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9388 hERG inhibition (predictor II) Inhibitor 0.6284
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 225.60268 predictedDeepCCS 1.0 (2019) [M+H]+ 227.55293 predictedDeepCCS 1.0 (2019) [M+Na]+ 233.39737 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Protein heterodimerization activity
- Specific Function
- Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:23475612, PubMed:8939939, PubMed:26224785, PubMed:25108285, PubMed:22236406). Requ...
- Gene Name
- MTTP
- Uniprot ID
- P55157
- Uniprot Name
- Microsomal triglyceride transfer protein large subunit
- Molecular Weight
- 99350.255 Da
References
- Ueshima K, Akihisa-Umeno H, Nagayoshi A, Takakura S, Matsuo M, Mutoh S: Implitapide, a microsomal triglyceride transfer protein inhibitor, reduces progression of atherosclerosis in apolipoprotein E knockout mice fed a Western-type diet: involvement of the inhibition of postprandial triglyceride elevation. Biol Pharm Bull. 2005 Feb;28(2):247-52. [Article]
Drug created at October 18, 2007 23:15 / Updated at May 04, 2023 00:49