Creative Biolabs offers PMX-53 development services in a timely and cost-effective manner. With years of ample experiences in antibody drug development, our scientists are confident in providing a full range of PMX-53 development services to promote the development for complement related biopharmaceuticals. We offer turn-key or ala carte services customized to our clients’ demands.
PMX53-C5aR Antagonist
Complement activation produced large amounts of C5a, which regulates immune activation and takes part in various pathophysiological progress via binding to C5a receptor (C5aR). The C5a-C5aR signaling pathway can be inhibited by C5aR antagonist-PMX53. It is a full C5aR antagonist of nanomolar potency and is widely used to study C5aR function in disease. The hexapeptide PMX53 has the sequence of Ace-Phe-[Orn-Pro-dCha-Trp-Arg], among which Ace denotes the blocking group CH3-CO at the N-terminal end, Orn ornithine, dCha d-cyclohexyl-alanine. Besides, the brackets denote cyclization of the main-chain via a covalent bond between the Orn side-chain and the Arg6 carbonyl group. Based on that, biopharmaceutical discovery of peptide, peptidomimetic, and organic compound antagonists of C5aR for targeting of complement-mediated autoimmune and inflammatory diseases is meaningful and has superior ADMET (absorption, distribution, metabolism, excretion, and toxicity) characteristics compared to other drugs and therefore be much more amenable to clinical development.
Fig.1 Structure of the cyclic hexapeptide ligand PMX53. (Tamamis, 2014)
PMX53 Protects Spinal Cord from Ischemia-reperfusion Injury
Spinal cord ischemia-reperfusion injury (SIRI) mainly occurs after operations on the descending thoracic or thoracoabdominal aorta, such as thoracoabdominal aneurysm. SIRI causes various complications, such as paraplegia and paraparesis. These complications have been attributed to temporary or permanent ischemia of the spinal cord caused by interruption of the blood supply during aortic cross-clamping. The C5a-C5aR signaling pathway can be activated in cerebral ischemia reperfusion after stroke and C5aR antagonist (PMX53) protects the brain from SIRI. It has been demonstrated that PMX53 protected SIRI in the heart, liver, kidneys, limb and small intestine. So, pre-treatment with PMX53 protected SIRI possibly via the inhibition of the C5a-C5aR signaling pathway. As a consequence, PMX53 can serve as a therapeutical choice for protecting spinal cord after ischemia-reperfusion injury.
Combination Effects of PMX53 and Argatroban after ICH Treatment
Intracerebral hemorrhage (ICH) is a subtype of stroke that associated with inflammation and neurological dysfunction, which can be ameliorated by a neuroprotective strategy targeting the complement cascade. Administration of a combination of PMX53 and argatroban provides a synergistic neuroprotective effect via reducing inflammatory factors and brain edema, leading to improvements in neurofunctional outcome. Treatment of the combination can also attenuate the brain injury secondary to ICH. The inhibition function of PMX53 would reduce C5a-induced inflammation in brain tissue, the development of which is meaningful for biopharmaceuticals.
Based on our advanced PMX53 development services strategy and well-developed platforms, Creative Biolabs is confident in proving customized PMX53 development services against a variety of complement component, especially for those which are essential for complement activities. Please contact us for more information or a detailed quotation.
Reference
1. Tamamis, P. Insights into the mechanism of C5aR inhibition by PMX53 via implicit solvent molecular dynamics simulations and docking. BMC biophysics. 2014, 7(1): 5.
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