Inclacumab Overview

Introduction of Inclacumab

Inclacumab is an IgG4 type human monoclonal antibody that inhibits P-selectin, which functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells. This drug was developed by Genentech/Roche to reduce the inflammation and heart tissue damage that often occurs during heart surgery when opening up clogged arteries. Global Blood Therapeutics is licensed the drug and plants to investigate the effects of the drug on the vaso-occlusive crisis, a painful complication of sickle cell disease as a complement to its lead investigational oral, voxelotor.

Actually, this drug has been investigated in trials studying the treatment and prevention of multiple cardiovascular diseases ethnic differences such as myocardial infarction, peripheral arterial disease (PAD), and coronary heart disease, graft occlusion, vascular. The preclinical and clinical study to investigate the effects of inclacumab on the interactions between leukocytes and platelets was conducted five years ago. And inclacumab was considered as an effective treatment for cardiovascular diseases through repressing the interaction of platelet-leukocyte. Another study evaluated the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction of inclacumab conducted at the same year, and this drug appears to reduce myocardial damage after PCI. Then, a crossover study evaluated the pharmacodynamic interaction between inclacumab and heparin in 18 healthy smokers and demonstrated that inclacumab did not affect the anticoagulant effect of unfractionated heparin. A study aimed to investigate the difference in the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single intravenous doses of inclacumab between healthy Japanese and Caucasian volunteers was conducted. The result showed that there is no ethnic differences clinically relevant influence on inclacumab. In addition, a study aimed to assess the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and PCI has conducted in 2016, with a conc myocardial lusion that 20 mg/kg of inclacumab significantly reduces myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction, and benefits are larger when the infusion is administered <3 hours before PCI.

Mechanism of Action of Inclacumab

Inclacumab was designed to bind to P-selectin, a protein that stored in α-granules of platelets and in Weibel–Palade bodies of endothelial cells when the platelets and endothelial cells are inactivated. P-selectin is found on the surface of endothelial cells (cells lining the inner walls of blood vessels) and in platelets. Ligands for P-selectin are proteins known as P-selectin glycoprotein ligand-1 (PSGL-1), heparan sulfate and fucoidan. A number of studies have shown that P-selectin interacts with circulating cancer cells at an early stage of metastasis in cancer dissemination. In addition, P-selectin is also found to play an important role in the initial recruitment of leukocytes (white blood cells) to the site of injury during inflammation and in in the recruitment and aggregation of platelets at areas of vascular injury. The function of P-selectin is to control the flow of white blood cells through blood vessels, and how they adhere to vessel walls, during periods of inflammation and tissue repair. And in sickle cell anemia, it is found to increase the rate of the adhesion of sickle red blood cells to blood vessels, preventing blood flow through smaller vessels and causing inflammation and pain crises. Inclacumab is a laboratory monoclonal antibody binds to P-selectin, blocking its interaction with ligands on neutrophils and monocytes. Under administration, this drug binds to P-selectin and inhibits platelet aggregation, maintains normal blood flow and minimize sickle cell-related pain crises (SCPC).

Fig.1 Mechanism of action of Inclacumab

What We Provide

Therapeutic Antibody

Inclacumab

We provide high-quality Inclacumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

For research use only. Not intended for any clinical use.