RIPK1: Promising Drug Target of Chronic Inflammatory Diseases

Today’s post is written by Michael Curtin, Senior Product Manager, Reporters and Signaling.

Inflammation is a defense mechanism that the body employs in which the immune system recognizes and removes harmful and foreign stimuli and begins the healing process. Inflammation can be either acute or chronic. Chronic inflammation is also referred to as slow, long-term inflammation and can last for prolonged periods (several months to years); chronic inflammation is caused by immune dysregulation. This typically takes the form of the body’s inability to resolve inflammation resulting from overproduction of inflammatory cytokines and chemokines, as well as danger-associated molecular patterns (DAMPs) released from dying cells (2). Tumor Necrosis Factor (TNF) is the primary cytokine involved in many common inflammatory diseases and is where many therapies targeting inflammation are focused.

Signaling of kinases like RIPK1 can be studied using the NanoBRET target engagement assays

Recent research that RIP kinases (RIPK1 and RIPK3) are important regulators of innate immunity via their key roles in cell death signaling during cellular stress and following exposure to inflammatory and infectious stimuli. RIPK1 has an important scaffolding role in pro-inflammatory signaling where it interacts with TRADD, TRAF1 TRAF2, and TRAF3 and TRADD can act as an adaptor protein to recruit RIPK1 to the TNFR1 complex in a TNF-dependent process. RIPK1 plays a kinase activity-dependent role in both apoptotic and necroptotic cell death. A review article by Speir et al. (1) discusses the role of RIP kinases in chronic inflammation and the potential of RIPK1 inhibitors as a new therapeutic approach for the treatment of chronic inflammation. RIPK1 or Receptor Interacting Protein Kinase 1 is a serine/threonine kinase that was originally identified as interacting with the cytoplasmic domain of FAS. Promega offers several reagents that make studying RIPK1 easier- these include our RIPK1 Kinase Enzyme Systems which includes RIPK1 (Human, recombinant; amino acids 1-327), myelin basic protein (MBP) substrate, reaction buffer, MnCl2, and DTT and is optimized for use with our ADP-Glo Kinase Assay.

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Paving New Ways for Drug Discovery & Development: Targeted Protein Degradation

The Dana-Farber Targeted Protein Degradation Webinar Series discusses new discoveries and modalities in protein degradation.

In this webinar, Senior Research Scientist, Dr. Danette Daniels, focuses primarily on proteolysis-targeting chimeras, or PROTACs. A variety of topics are covered including the design, potency, and efficacy of PROTACs in targeted protein degradation. Watch the video below to learn more about how PROTACs are shifting perspectives through fascinating research and discoveries in targeted protein degradation.

Learn more about targeted protein degradation and PROTACS here.

GPCR Targets are a Dimer a Dozen

G protein-coupled receptors (GPCRs) are the most prevalent gene family in the human genome. They are involved with everything from our sense of smell to immune system function to tumor growth. Unsurprisingly, GPCRs have been a hotbed for research and development. Of the 7,038 approved drugs analyzed for this blog post, I found that 29% of them target Class A (Rhodopsin-like) GPCRs, and 35% target any GPCR. In the spirit of Internet pop culture, I made a “quiz” to see if you can guess the top 10 receptors by their ligand’s chemical structure.

Can you guess these GPCR receptors by their ligand chemical structures?

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