Inupadenant is an Orally Active and Highly Selective A2A Receptor Antagonist

Adenosine receptors (AR), including P1 purinergic receptors, belong to G protein-coupled receptors (GPCR). Specifically, Adenosine is an autogenous acid in all tissues and body fluids. Besides, AR contains four subtypes, A1, A2A, A2B, and A3. They are activated by extracellular adenosine and play a central role in a wide...

ABBV-744 is a First-in-Class, Orally Active and Selective BET BDII Inhibitor

The proteins of BET (bromodomain and extra-terminal) domain family are epigenetic readers. BET domain family proteins bind acetylated histones through their bromodomains to regulate gene transcription. BET domain family proteins consist of BRD2, BRD3, BRD4 and BRDT. They contain BDI, BDII and the extra-terminal (ET) domain. Interestingly, BDII of...

DP-C-4 is a CRBN-Based dual PROTAC for EGFR and PARP

Proteolysis targeting chimera (PROTAC) is a bifunctional small molecule. Interestingly, dual PROPACs are dual-targeted degradation molecules that combine the concepts of PROTAC and dual-targeting. Dual PROPACs degrade two completely different pathway targets while simultaneously taking advantage of both PROTAC and dual-target drugs. Thus, dual PROPACs not only achieve the...

SJ6986 is a Selective and Orally Active GSPT1/2 Degrader

Targeted protein degradation (TPD) is a novel chemical biology approach. Molecular glues (MGs) are small molecules that can bind to E3 ligase and change their surface and specificity, leading to the recruitment, ubiquitination, and subsequent degradation of substrates that are normally not targeted by the ligase (neosubstrates). Immunomodulatory imide...

Lumiracoxib is a Selective and Orally Active COX-2 Inhibitor and Nonselective NSAID

Prostaglandins play an important role in modulating both physiological and inflammatory processes. They can act as autocrine factors regulating platelet aggregation, vascular tone, and secretions. Additionally, the synthesis of prostaglandin depends on the activity of cyclooxygenase (COX). There are existing two isoforms: COX-1 and COX-2. They are highly homologous...

GL0388 Activates Bax and Induce Bax-Mediated Apoptosis

Bax is a member of the bcl-2 gene family. Specifically, BCL2 family members are relevant to a variety of anti-apoptotic or pro-apoptotic regulators. The expression of this gene is regulated by the tumor suppressor gene p53. Besides, Bax interacts with mitochondrial voltage-dependent anion channel VDAC and induces its opening....

BSJ-4-116 is a Highly Potent and Selective PROTAC Based CDK12 Degrader

CDKs are serine/threonine protein kinases. They play major roles in regulating many different aspects of mammalian cellular function, most notably cell cycle and transcription. CDK12 is an emerging therapeutic target due to its role in regulating the transcription of DNA-damage response (DDR) genes. For example, ovarian and triple-negative breast...