This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
KP-1461
Accession Number
DB05644
Type
Small Molecule
Groups
Investigational
Description

KP-1461 is a potent, non-chain-terminating, mutagenic deoxyribonucleoside analogue. Designated a DNA covert nucleoside, the drug consists of a modified base that incorporates randomly into HIV and pairs with multiple bases.

Structure
Thumb
Synonyms
  • SN1212
Categories
UNII
3PEN569TJP
CAS number
815588-85-3
Weight
Average: 372.422
Monoisotopic: 372.200884638
Chemical Formula
C16H28N4O6
InChI Key
SZWIAFVYPPMZML-YNEHKIRRSA-N
InChI
InChI=1S/C16H28N4O6/c1-2-3-4-5-6-7-25-16(24)19-14-17-10-20(15(23)18-14)13-8-11(22)12(9-21)26-13/h11-13,21-22H,2-10H2,1H3,(H2,17,18,19,23,24)/t11-,12+,13+/m0/s1
IUPAC Name
heptyl N-{5-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-oxo-1,4,5,6-tetrahydro-1,3,5-triazin-2-yl}carbamate
SMILES
CCCCCCCOC(=O)NC1=NC(=O)N(CN1)[C@H]1C[C@H](O)[C@@H](CO)O1

Pharmacology

Indication

Investigated for use/treatment in HIV infection.

Pharmacodynamics
Not Available
Mechanism of action

KP-1461 is the oral prodrug of KP-1212. KP-1461 is also known as SN1212. KP-1461 introduces continual mutations into HIV during viral replication by reverse transcriptase (RT). These mutations decrease virus viability and are eventually lethal. This mechanism, selective viral mutagenesis or lethal mutagenesis, is novel to the nucleoside analogue class. Unlike approved nucleoside RT inhibitors (NRTIs) that contain a modified sugar and unmodified base, KP-1461 has a modified base that allows multiple base pairing. Because KP-1461 pairs with multiple bases, it is able to target all viral proteins rather than a single protein. KP-1461, after conversion to KP-1212, is metabolized to a triphosphate and incorporated into the HIV-1 genome by RT. The drug is similarly incorporated into human mitochondrial DNA polymerase. The active substance KP-1212 has been shown to inhibit antiviral activity in tissues after just one pass; accumulation has been shown to eradicate the virus entirely. HIV strains treated with KP-1212 also showed increased sensitivity to zidovudine.

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
  1. Harris KS, Brabant W, Styrchak S, Gall A, Daifuku R: KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis. Antiviral Res. 2005 Jul;67(1):1-9. [PubMed:15890415]
  2. Becker S: New kind of antiretroviral, KP-1461; clinical trial recruiting. Interview with Stephen Becker, M.D. AIDS Treat News. 2007 Jul-Sep;(423):3-7. [PubMed:18411488]
External Links
ChemSpider
32702166
Wikipedia
Error_catastrophe

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1

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 Solubility1.03 mg/mLALOGPS
logP0.47ALOGPS
logP0.96ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)5.9ChemAxon
pKa (Strongest Basic)2.42ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area132.72 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity89.83 m3·mol-1ChemAxon
Polarizability39.6 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
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

Classification
Not classified

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
P03369
Uniprot Name
Gag-Pol polyprotein
Molecular Weight
162014.15 Da
References
  1. Harris KS, Brabant W, Styrchak S, Gall A, Daifuku R: KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis. Antiviral Res. 2005 Jul;67(1):1-9. [PubMed:15890415]

Drug created on November 18, 2007 11:26 / Updated on November 02, 2018 06:11