Author: Quan, Shuo ; Adam, Gregory C. ; Schwaid, Adam G. ; Hollenstein, Kaspar ; Diamond, Tracy L. ; Anand, Rajan ; Carroll, Steven S. ; Moningka, Remond ; Beshore, Douglas C. ; Moore, Keith P. ; Goh, Shih Lin ; Shipe, William D. ; Rothman, Deborah M. ; Lim, U-Ming ; Howell, Bonnie J. ; Tudor, Matthew ; Xu, Min ; Klein, Daniel J. ; Fay, John F. ; Rodriguez, Silveria ; Lammens, Alfred ; Li, Jing ; Cornella-Taracido, Ivan ; Lan, Ping ; Park, Sangho ; Lu, Meiqing ; Zuck, Paul ; Converso, Antonella ; Filzen, Tracey ; McHale, Carolyn ; Li, Yuan ; Fang, Zhiyu ; Andrews, Christine L. ; Balibar, Carl J. ; Song, Cheng ; Chi, An ; Lusen, Jeffrey ; Sun, Wanying ; Bahnck-Teets, Carolyn

Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that can lead to eradication of persistent viral reservoirs in people living with HIV-1 (PLWH) remains an outstanding challenge to achieving cure. Utilizing a phenotypic screen, we identified a novel chemical class capable of killing HIV-1 infected peripheral blood mononuclear cells. Tool compounds ICeD-1 and ICeD-2 ("inducer of cell death-1 and 2"), optimized for potency and selectivity from screening hits, were used to deconvolute the mechanism of action using a combination of chemoproteomic, biochemical, pharmacological, and genetic approaches. We determined that these compounds function by modulating dipeptidyl peptidase 9 (DPP9) and activating the caspase recruitment domain family member 8 (CARD8) inflammasome. Efficacy of ICeD-1 and ICeD-2 was dependent on HIV-1 protease activity and synergistic with efavirenz, which promotes premature activation of HIV-1 protease at high concentrations in infected cells. This in vitro synergy lowers the efficacious cell kill concentration of efavirenz to a clinically relevant dose at concentrations of ICeD-1 or ICeD-2 that do not result in complete DPP9 inhibition. These results suggest engagement of the pyroptotic pathway as a potential approach to eliminate HIV-1 infected cells.

100 Deals associated with ICeD-2

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Preclinical	United States	Merck & Co., Inc.	31 Aug 2022
HIV Infections	Preclinical	Germany	Proteros biostructures GmbH	31 Aug 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

ICeD-2

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation