KP-1461
Identification
- Generic Name
- KP-1461
- DrugBank Accession Number
- DB05644
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 372.422
Monoisotopic: 372.200884638 - Chemical Formula
- C16H28N4O6
- Synonyms
- Not Available
- External IDs
- KP 1461
- KP-1461
- SN1212
Pharmacology
- Indication
Investigated for use/treatment in HIV infection.
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- 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.
Target Actions Organism UGag-Pol polyprotein Not Available HIV-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
- Adverse Effects
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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 pentoses. These are monosaccharides in which the carbohydrate moiety contains five carbon atoms.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbohydrates and carbohydrate conjugates
- Direct Parent
- Pentoses
- Alternative Parents
- Triazinones / 1,3,5-triazines / Tetrahydrofurans / Carbamate esters / Ureas / Secondary alcohols / Guanidines / Propargyl-type 1,3-dipolar organic compounds / Oxacyclic compounds / Carboximidamides show 7 more
- Substituents
- 1,3,5-triazine / Alcohol / Aliphatic heteromonocyclic compound / Azacycle / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Carboximidamide / Guanidine / Hydrocarbon derivative show 16 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 3PEN569TJP
- CAS number
- 815588-85-3
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- External Links
- ChemSpider
- 32702166
- Wikipedia
- Error_catastrophe
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Terminated Treatment Human Immunodeficiency Virus (HIV) Infections 1 1 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 1
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 1.03 mg/mL ALOGPS logP 0.47 ALOGPS logP 0.96 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) 9.9 Chemaxon pKa (Strongest Basic) 2.82 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 132.72 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 89.83 m3·mol-1 Chemaxon Polarizability 39.64 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0592000000-dfc99804306181b7a10d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-1159000000-b2cdd77054c8346ca2f8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0930000000-b5e23636e3f84008e947 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0079-3974000000-9efb370b84c2de60e300 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0930000000-c636ef55a8513f05acc4 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-090c-2971000000-9c1fbc8457c6eafb5d75 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 193.47427 predictedDeepCCS 1.0 (2019) [M+H]+ 196.78734 predictedDeepCCS 1.0 (2019) [M+Na]+ 205.35265 predictedDeepCCS 1.0 (2019)
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
- 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. [Article]
Drug created at November 18, 2007 18:26 / Updated at June 12, 2020 16:52