Dapivirine

Identification

Name
Dapivirine
Accession Number
DB08639  (DB11908)
Type
Small Molecule
Groups
Investigational
Description

Dapivirine has been investigated for the prevention of HIV-1 Infections and Topical Penile Exposures.

Structure
Thumb
Synonyms
Not Available
External IDs
AIDS-105293 / R-147681 / TMC-120 / TMC120
Product Ingredients
IngredientUNIICASInChI Key
Dapivirine hydrochloride55D48BY90H244768-47-6RHIYZDNOTUMYCA-UHFFFAOYSA-N
Categories
Not Available
UNII
TCN4MG2VXS
CAS number
244767-67-7
Weight
Average: 329.3984
Monoisotopic: 329.164045633
Chemical Formula
C20H19N5
InChI Key
ILAYIAGXTHKHNT-UHFFFAOYSA-N
InChI
InChI=1S/C20H19N5/c1-13-10-14(2)19(15(3)11-13)24-18-8-9-22-20(25-18)23-17-6-4-16(12-21)5-7-17/h4-11H,1-3H3,(H2,22,23,24,25)
IUPAC Name
4-({4-[(2,4,6-trimethylphenyl)amino]pyrimidin-2-yl}amino)benzonitrile
SMILES
CC1=CC(C)=C(NC2=NC(NC3=CC=C(C=C3)C#N)=NC=C2)C(C)=C1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UGag-Pol polyproteinNot AvailableHIV-1
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
Not Available
External Links
PubChem Compound
214347
PubChem Substance
99445110
ChemSpider
185837
ChEMBL
CHEMBL70663
HET
TPB
Wikipedia
Dapivirine
PDB Entries
1s6q

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionHIV Prevention1
1CompletedPreventionHuman Immunodeficiency Virus (HIV)2
1CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections3
1CompletedPreventionPharmaokinetics1
1CompletedPreventionTopical Penile Exposures1
1Not Yet RecruitingPreventionHuman Immunodeficiency Virus (HIV) Infections1
1RecruitingPreventionHuman Immunodeficiency Virus (HIV) Infections1
1WithdrawnOtherHIV 1 Infection1
1WithdrawnPreventionHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedPreventionAcquired Immune Deficiency Syndrome (AIDS) / Healthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1, 2CompletedPreventionAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
1, 2CompletedPreventionInfection, Human Immunodeficiency Virus I1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) / Safety1
2WithdrawnPreventionHIV-1-infection1
3WithdrawnPreventionHuman Immunodeficiency Virus (HIV) Infections2

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 Solubility0.017 mg/mLALOGPS
logP4.12ALOGPS
logP5.6ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)12.93ChemAxon
pKa (Strongest Basic)5.16ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area73.63 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity100.8 m3·mol-1ChemAxon
Polarizability37.16 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.984
Blood Brain Barrier+0.8503
Caco-2 permeable+0.6773
P-glycoprotein substrateNon-substrate0.73
P-glycoprotein inhibitor INon-inhibitor0.7381
P-glycoprotein inhibitor IINon-inhibitor0.7798
Renal organic cation transporterNon-inhibitor0.84
CYP450 2C9 substrateNon-substrate0.8026
CYP450 2D6 substrateNon-substrate0.8019
CYP450 3A4 substrateNon-substrate0.6521
CYP450 1A2 substrateInhibitor0.7843
CYP450 2C9 inhibitorNon-inhibitor0.9177
CYP450 2D6 inhibitorNon-inhibitor0.8807
CYP450 2C19 inhibitorNon-inhibitor0.7548
CYP450 3A4 inhibitorNon-inhibitor0.8598
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5896
Ames testNon AMES toxic0.7603
CarcinogenicityNon-carcinogens0.907
BiodegradationNot ready biodegradable0.9973
Rat acute toxicity2.8549 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9178
hERG inhibition (predictor II)Non-inhibitor0.7945
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzonitriles
Direct Parent
Benzonitriles
Alternative Parents
Aniline and substituted anilines / Aminopyrimidines and derivatives / Imidolactams / Heteroaromatic compounds / Secondary amines / Nitriles / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Benzonitrile / Aniline or substituted anilines / Aminopyrimidine / Pyrimidine / Imidolactam / Heteroaromatic compound / Carbonitrile / Nitrile / Secondary amine / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aminopyrimidine, nitrile (CHEBI:46180)

Targets

Kind
Protein
Organism
HIV-1
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Gag-Pol polyprotein: Mediates, with Gag polyrotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spher...
Gene Name
gag-pol
Uniprot ID
P03366
Uniprot Name
Gag-Pol polyprotein
Molecular Weight
163287.51 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on September 15, 2010 15:33 / Updated on October 01, 2018 16:52