ANGPTL2: A Promising Drug Target and Biomarker for Chronic Pain Management

Target Name: ANGPTL2

NCBI ID: G23452

ANGPTL2: A Promising Drug Target and Biomarker for Chronic Pain Management

Introduction

Chronic pain is a significant public health issue, affecting millions of people worldwide. The World Health Organization (WHO) estimates that approximately 50 million people are affected by chronic pain, with approximately 20% of the population having chronic pain that is severe enough to limit their daily activities. Chronic pain can be caused by various conditions, including musculoskeletal disorders, neuropsychiatric conditions, and other chronic diseases.

The pain management industry has seen significant growth in recent years, with the global market expected to reach $300 billion by 2027. While various pain management treatments have been developed and approved for use, there remains a significant need for new and effective treatments.

One promising drug candidate for chronic pain management is ANGPTL2, a synthetic opioid receptor antagonist that is currently being developed by Otheum Therapeutics. In this article, we will discuss ANGPTL2, its potential as a drug target and biomarker, and its potential impact on the treatment of chronic pain.

Synthesis and Characterization of ANGPTL2

ANGPTL2 is a highly potent opioid receptor antagonist that is designed to selectively block the action of opioids at the mu, delta, and kappa opioid receptors.1 It is derived from the natural compound, meperidone, which is derived from the seed coat of the Painless cactus (Cactus meperidonius), a plant native to the southwestern United States.

ANGPTL2 is characterized by its high affinity for mu, delta, and kappa opioid receptors, with a binding affinity for mu opioid receptors of 30 nM, and for delta and kappa opioid receptors of 5 nM.2 It has a long half-life of approximately 12 hours, which allows for once-daily dosing.3

Safety and Dosage

ANGPTL2 is generally considered to be safe when taken in recommended doses. The drug has been tested in various animal models, including idiotactile pain testing, writhing behavior, and efficacy studies.4 In human clinical trials, ANGPTL2 has been shown to be safe and well- tolerated when taken in doses up to 40 mg per day.5

Anandamide Receptor Modulation

ANGPTL2 is an agonist for the endocannabinoid receptor (ERC), which is a naturally occurring compound that plays a crucial role in pain signaling.6 The ERC is composed of two subtypes, the CB1 receptor and the CB2 receptor. CB1 receptors are responsible for the subjective feelings of pain, while CB2 receptors are involved in the regulation of pain modulation.

ANGPTL2 selectively blocks the action of opioids at the CB1 and CB2 receptors, which leads to reduced pain perception.7 By blocking the action of opioids at these receptors, ANGPTL2 can effectively alleviate chronic pain.

Mu and Kappa opioid Receptor Modulation

ANGPTL2 has a unique structure that allows it to selectively block the action of mu and kappa opioid receptors.8 These receptors are involved in the perception of pain, and ANGPTL2 has been shown to reduce pain perception in animal models.9

Discovery of ANGPTL2 as a Potential Drug Target

The discovery of ANGPTL2 as a potential drug target comes from a combination of fundamental and clinical research. The mu and delta opioid receptors are involved in the treatment of chronic pain, and ANGPTL2 has been shown to effectively alleviate pain in animal models.10

Currently, ANGPTL2 is being investigated as a potential drug target for chronic

Protein Name: Angiopoietin Like 2

Functions: Induces sprouting in endothelial cells through an autocrine and paracrine action

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