Business Strategy/ IgE inhibitor / Interprotein

IgE inhibitor
Since the complex of allergen, IgE and IgE receptor triggers allergic reaction, many pharmaceutical companies had tried to develop anti-allergic drugs targeting this complex. Of such companies, Tanox reached success to develop anti-IgE antibody, omalizumab, and has obtained a great sales even though it is prescribed for only patients with severe asthma.
Omalizumab is a boon to sever asthmatic patients, however, it is somewhat expensive (over $430/150 mg/vial as wholesales price) and therapeutic cost for a patient is beyond $10,000/year. Based on these circumstances, we considered if we would develop a small molecule inhibitor against protein-protein interaction (PPI) of IgE and its receptor, FcεRI, we could provide a novel therapeutic option to sever asthmatic patients, and, as a result, contribute to the reduction of therapeutic cost by substituting it for omalizumab and/or decrease the dosage of omalizumab.
In this project, we designed compounds that would inhibit a binding of Cε3 domain of IgE to α2 (D2) domain of FcεRI α chain by closest packing approach for drug design (CPADD) method, and 41,169 compounds were selected from data base. The compounds were eventually narrowed down to 124 compounds through several steps including judgment of druglikeness and these selected compounds were evaluated as follows:
We established rat basophile leukemia cell line (RBL-2H3) that constitutively expresses human FceRI α chain and evaluated effect of test compounds on human IgE-induced degranulation of the cells. As a marker of degranulation, enzymatic activity of β-hexosaminidase in culture supernatant and cell lysate was measured with p-nitrophenyl-N-acetyl-β-D-glucopyranoside (PNAG), a substrate for β-hexosaminidase. Active compounds showed concentration-dependent inhibition of human IgE-induced degranulation of RBL-2H3 cells.