A Selective COX-2 Inhibitor
Cyclooxygenase (COX) is an enzyme that is responsible for production of prostanoids, including thromboxane and prostaglandins (PGs). PGs promote inflammation, pain, and fever. Selective COX-2 inhibitor is a subclass of NSAIDs, which inhibits the formation of PGs to reduce inflammation, pain, and fever.
Imrecoxib is a highly selective COX-2 inhibitor approved in China in 2011, which relieves the pain induced by osteoarthritis.
A Short-Lasting GABAα Receptor Agonist
Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in mammalian central nervous system. Activation of GABA receptors results in neural inhibition, reducing neuronal excitability, sedation, and amnesia etc.
HR7056 is a short-lasting GABAα receptor agonist for anesthesia and conscious sedation for minor invasive procedures. NDA for HR7056 was filed in March 2018 in China and is expected to be approved in 2019.
A Novel Biased MOR Agonist for the Treatment of Postoperative Pain
Traditional μ-opioid receptor (MOR) agonists simultaneously activate G-protein coupling and β-arrestin-2 recruitment, resulting in analgesia as well as related adverse effects. The adverse effects, such as respiratory and gastrointestinal dysfunction, limit the use of MOR agonists in clinic.
SHR8554 is a novel biased MOR agonist for the treatment of acute pain. It activates MOR-mediated G-protein coupling, but barely recruits β-arrestin-2. SHR8554 demonstrated remarkable analgesic effects in a variety of acute pain models with significant improvement in GI dysfunction.
SHR8554 is currently being evaluated in a phase I clinical trial in China.
A Novel Selective KOR Agonist for the Treatment of Pain
Kappa-opioid receptor (KOR) is a subtype of opioid receptor. The effect of KOR agonist is mediated by its action at KOR on dorsal root ganglion (anti-nociceptive), immune cells (anti-inflammatory), and sensory nerves (anti-nociceptive and anti-pruritic). In contrast to μ and δ opioid receptor agonists，κ opioid receptor agonists exhibit analgesic effect without addiction and tolerance liability. However, activation of KOR in the central nervous system (CNS) produces undesirable effects such as dysphoria, anhedonia, and hallucinations. Unlike brain-accessible KOR agonists, peripherally restricted KOR agonists have been demonstrated to reduce both visceral and somatic pain without CNS side effects.
SHR0410 is a highly potent and selective peripheral KOR agonist for the treatment of pain with minimal MOR-mediated and CNS-related adverse effects. SHR0410 demonstrated an encouraging safety profile in animal models. It exhibited analgesic effects in animal models of incisional pain, neuropathic pain, visceral pain, and inflammatory pain, as well as anti-pruritic effects in animal models of induced pruritus.
SHR0410 is currently being evaluated in the phase I clinical trials in China and Australia.