Orally bioavailable STING antagonist synthesized via multi-component Povarov-Doebner type reaction

Kofi B Owusu; Jyotrimayee Samal; Delmis E Hernandez; Herman O Sintim

doi:10.1039/d4cc03228d

Orally bioavailable STING antagonist synthesized via multi-component Povarov-Doebner type reaction

Chem Commun (Camb). 2024 Oct 15;60(83):11932-11935. doi: 10.1039/d4cc03228d.

Authors

Kofi B Owusu^{1

2}, Jyotrimayee Samal^{1

2}, Delmis E Hernandez¹, Herman O Sintim^{1

2

3}

Affiliations

¹ Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA. hsintim@purdue.edu.
² Institute for Drug Discovery, Purdue University, 720 Clinic Drive, West Lafayette, Indiana 47907, USA.
³ Purdue Institute of Inflammation, Immunology, and Infectious Disease, West Lafayette, IN, 47907, USA.

PMID: 39344905
DOI: 10.1039/d4cc03228d

Abstract

Aberrant activation of the cGAS-STING signaling results in innate immune response induction. Herein, we report HSKB142, an orally bioavailable compound containing the 3H-pyrazolo [4,3-f]quinoline synthesized via a Povarov-Doebner MCR. HSKB142 is non-cytotoxic towards immune cells and suppresses type-1 interferon expression in human THP-1 monocytes upon treatment with 2'3'-cGAMP.

MeSH terms

Administration, Oral
Humans
Interferon Type I / metabolism
Membrane Proteins* / antagonists & inhibitors
Membrane Proteins* / metabolism
Molecular Structure
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology
Quinolines / chemistry
Quinolines / pharmacology
THP-1 Cells

Substances

STING1 protein, human
Membrane Proteins
Quinolines
Pyrazoles
Interferon Type I