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
Thumb
Weight
Average: 531.6872
Monoisotopic: 531.288577443
Chemical Formula
C35H37N3O2
Synonyms
  • Implitapide
External IDs
  • BAY-13-9952

Pharmacology

Indication

For the treatment of atherosclerosis.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
UMicrosomal triglyceride transfer protein large subunitNot AvailableHumans
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
Adverseeffects
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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
  1. Pahan K: Lipid-lowering drugs. Cell Mol Life Sci. 2006 May;63(10):1165-78. [Article]
  2. Iglesias P, Diez JJ: New drugs for the treatment of hypercholesterolaemia. Expert Opin Investig Drugs. 2003 Nov;12(11):1777-89. [Article]
  3. 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]
PubChem Compound
5745206
PubChem Substance
175426863
ChemSpider
4676524
ChEMBL
CHEMBL2105804
ZINC
ZINC000059676426

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentHypertriglyceridemias1
2TerminatedTreatmentPrimary Hypercholesterolemia2

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 Solubility0.000202 mg/mLALOGPS
logP6.43ALOGPS
logP6.68ChemAxon
logS-6.4ALOGPS
pKa (Strongest Acidic)13.4ChemAxon
pKa (Strongest Basic)4.35ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.15 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity160.14 m3·mol-1ChemAxon
Polarizability59.8 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9789
Blood Brain Barrier+0.737
Caco-2 permeable-0.7737
P-glycoprotein substrateSubstrate0.7286
P-glycoprotein inhibitor INon-inhibitor0.875
P-glycoprotein inhibitor IINon-inhibitor0.6584
Renal organic cation transporterNon-inhibitor0.7036
CYP450 2C9 substrateNon-substrate0.7341
CYP450 2D6 substrateNon-substrate0.732
CYP450 3A4 substrateNon-substrate0.5165
CYP450 1A2 substrateInhibitor0.618
CYP450 2C9 inhibitorNon-inhibitor0.6956
CYP450 2D6 inhibitorNon-inhibitor0.8205
CYP450 2C19 inhibitorNon-inhibitor0.7036
CYP450 3A4 inhibitorNon-inhibitor0.8501
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5876
Ames testNon AMES toxic0.7231
CarcinogenicityNon-carcinogens0.917
BiodegradationNot ready biodegradable0.8258
Rat acute toxicity2.4158 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9388
hERG inhibition (predictor II)Inhibitor0.6284
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Targets

Drugtargets2
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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
  1. 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 on October 18, 2007 23:15 / Updated on February 21, 2021 18:51