Delving into the Latest Updates on ABI-1968 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ODE-BN-PMEG

+ [1]

Target-

Action

stimulants, inhibitors

Mechanism

Apoptosis stimulants, Virus replication inhibitors

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [3]

Active Indication-

Inactive Indication

Anal intraepithelial neoplasiaAnal Precancerous ConditionCervical Intraepithelial Neoplasia+ [5]

Originator Organization

Antiva Biosciences, Inc.

Active Organization-

Inactive Organization

Antiva Biosciences, Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC35H58N5O6P

InChIKeyAHSNBFKBLUUKAW-UHFFFAOYSA-N

CAS Registry1626364-18-8

The present study evaluated antiviral activity of ODE-Bn-PMEG, an acyclic nucleoside phosphonate prodrug against productive HPV-18 infection in 3D organotypic epithelial cultures.3D organotypic model system was prepared from raft cultures of primary human keratinocytes with HPV-18 genomic plasmid and cells were treated with ODE-Bn-PMEG.ODE-Bn-PMEG showed durable antiviral affects by inhibiting HPV-18 DNA amplification and cellular DNA replication and significantly reduced E7-mediated induction of PCNA and cyclin B1 and reduced viral DNA copy numbers/cell.ODE-Bn-PMEG induced DNA damage and apoptosis showing high percentage of γ-H2AX pos. nuclei and incidence of condensed nuclei in HPV-18 raft cultures.Cidofovir reduced HPV DNA amplification but did not significantly affect viral activity and also stabilized p53 to inhibit HPV-18 DNA amplification.This study concluded that ODE-Bn-PMEG at 1.5 μM has superior antiviral affects than cidofovir and blocked HPV DNA amplification, virion production and possibly viral persistence as well as causing apoptosis in suprabasal infected cells.

08 Dec 2016·Journal of Medicinal ChemistryQ1 · MEDICINE

Synthesis and Antiviral Evaluation of Octadecyloxyethyl Benzyl 9-[(2-Phosphonomethoxy)ethyl]guanine (ODE-Bn-PMEG), a Potent Inhibitor of Transient HPV DNA Amplification

Q1 · MEDICINE

Article

Author: Hartman, Tracy ; Keith, Kathy A. ; Chow, Louise T. ; Prichard, Mark N. ; Hostetler, Karl Y. ; Beadle, James R. ; Broker, Thomas R. ; Harden, Emma A. ; Aldern, Kathy A. ; Yang, Guang ; Valiaeva, Nadejda ; Buckheit, Robert W. ; Yu, Jei-Hwa

Human papillomavirus (HPV) high-risk genotypes such as HPV-16 and HPV-18 cause the majority of anogenital tract carcinomas, including cervical cancer, the second most common malignancy in women worldwide. Currently there are no approved antiviral agents that reduce or eliminate HPV and reverse virus-associated pathology. We synthesized and evaluated several alkoxyalkyl acyclic nucleoside phosphonate diesters and identified octadecyloxyethyl benzyl 9-[(2-phosphonomethoxy)ethyl]guanine (ODE-Bn-PMEG) as an active compound which strongly inhibited transient amplification of HPV-11, -16, and -18 origin-containing plasmid DNA in transfected cells at concentrations well below its cytotoxic concentrations. ODE-Bn-PMEG demonstrated increased uptake in human foreskin fibroblast cells and was readily converted in vitro to the active antiviral metabolite, PMEG diphosphate. The P-chiral enantiomers of ODE-Bn-PMEG were obtained and appeared to have equivalent antiviral activities against HPV. ODE-Bn-PMEG is a promising candidate for the local treatment of HPV-16 and HPV-18 and other high-risk types, an important unmet medical need.

100 Deals associated with ABI-1968

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Anal Precancerous Condition	Phase 1	Australia	Antiva Biosciences, Inc.	11 Aug 2017
Anal Precancerous Condition	Phase 1	United States	Antiva Biosciences, Inc.	11 Aug 2017
Chronic human papillomavirus (HPV) infection	Phase 1	Australia	Antiva Biosciences, Inc.	11 Aug 2017
Chronic human papillomavirus (HPV) infection	Phase 1	United States	Antiva Biosciences, Inc.	11 Aug 2017
Chronic human papillomavirus (HPV) infection	Phase 1	Australia	Antiva Biosciences, Inc.	11 Aug 2017
Chronic human papillomavirus (HPV) infection	Phase 1	United States	Antiva Biosciences, Inc.	11 Aug 2017
Squamous Intraepithelial Lesions	Phase 1	United States	Antiva Biosciences, Inc.	11 Aug 2017
Squamous Intraepithelial Lesions	Phase 1	Australia	Antiva Biosciences, Inc.	11 Aug 2017
Squamous Intraepithelial Lesions	Phase 1	United States	Antiva Biosciences, Inc.	11 Aug 2017
Squamous Intraepithelial Lesions	Phase 1	Australia	Antiva Biosciences, Inc.	11 Aug 2017