Delving into the Latest Updates on Cpd G with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

OSBPL7

Action

modulators

Mechanism

OSBPL7 modulators(oxysterol binding protein like 7 modulators)

Therapeutic Areas

Urogenital Diseases

Active Indication

Nephrosis

Inactive Indication-

Originator Organization

F. Hoffmann-La Roche Ltd.

Active Organization

F. Hoffmann-La Roche Ltd.

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC20H19Cl2F3N2O3

InChIKeyGYXGGHPMGUITOT-IAGOWNOFSA-N

CAS Registry1269826-44-9

Author: Merscher, Sandra ; Pedigo, Christopher ; Varona Santos, Javier ; Roever, Stephan ; Kemmer, Christian ; Mitrofanova, Alla ; Fornoni, Alessia ; Carralot, Jean-Philippe ; Pressly, Jeffrey ; Sloan, Alexis ; Ducasa, G Michelle ; Sgrignani, Jacopo ; Maugeais, Cyrille ; Wright, Matthew B ; Prunotto, Marco ; Cavalli, Andrea ; Mendez, Armando ; Barisoni, Laura ; Ahmad, Anis ; Molina, Judith ; Ge, Mengyuan

AbstractImpaired cellular cholesterol efflux is a key factor in the progression of renal, cardiovascular, and autoimmune diseases. Here we describe a class of 5-arylnicotinamide compounds, identified through phenotypic drug discovery, that upregulate ABCA1-dependent cholesterol efflux by targeting Oxysterol Binding Protein Like 7 (OSBPL7). OSBPL7 was identified as the molecular target of these compounds through a chemical biology approach, employing a photoactivatable 5-arylnicotinamide derivative in a cellular cross-linking/immunoprecipitation assay. Further evaluation of two compounds (Cpd A and Cpd G) showed that they induced ABCA1 and cholesterol efflux from podocytes in vitro and normalized proteinuria and prevented renal function decline in mouse models of proteinuric kidney disease: Adriamycin-induced nephropathy and Alport Syndrome. In conclusion, we show that small molecule drugs targeting OSBPL7 reveal an alternative mechanism to upregulate ABCA1, and may represent a promising new therapeutic strategy for the treatment of renal diseases and other disorders of cellular cholesterol homeostasis.

100 Deals associated with Cpd G

Login to view more data