In silico Insights on IL-6: A Potential Target for Multicentric Castleman Disease.

BACKGROUND: Multicentric Castleman Disease (MCD) is a confrontational lymphoproliferative disorder described by symptoms such as lymph node proliferation, unwarranted secretion of inflammatory cytokines, hyperactive immune system, and in severe cases, multiple organ dysfunction. Interleukin-6 (IL-6) is a pleiotropic cytokine which is involved in a large range of physiological processes in our body such as pro-inflammation, anti-inflammation, differentiation of T-cells and is reported to be a key pathological factor in MCD. In the case of MCD, it was observed that IL-6 is overproduced from T-cells and macrophages which disturb Hepcidin, a vital regulator of iron trafficking in macrophage. The present study endeavour to expound the inhibitor which binds to IL-6 protein receptor with high affinity. METHODS: MolegroVirtual Docker software was employed to find the best-established drug from the list of selected inhibitors of IL-6. This compound was subjected to virtual screening against PubChem database to get inhibitors with a very similar structure. These inhibitors were docked to obtain a compound binding with high affinity to the target protein. The established compound and the virtual screened compound were subjected to relative analysis of interactivity energy variables and ADMET profile studies. RESULTS: Among all the selected inhibitors, the virtual screened compound PubChem CID: 101119084 is seen to possess the highest affinity with the target protein. Comparative studies and ADMET analysis further implicate this compound as a better inhibitor of the IL-6 protein. CONCLUSION: Hence, this compound recognized in the study possesses high potential as an IL-6 inhibitor which might assist in the treatment of Multicentric Castleman Disease and should be examined for its efficiency by in vivo studies.

Design of novel JAK3 Inhibitors towards Rheumatoid Arthritis using molecular docking analysis.

Multiple cytokines play a pivotal role in the pathogenesis of Rheumatoid Arthritis by inducing intracellular signaling and it is known that the members of the Janus kinase (JAK) family are essential for such signal transduction. Janus kinase 3 is a tyrosine kinase that belongs to the Janus family of kinases. Drugs targeting JAK3 in the treatment of Rheumatoid arthritis is relevant. Therefore, it is of interest to design suitable inhibitors for JAK3 dimer using molecular docking with Molegro Virtual Docker. The compound possessing the highest affinity score is subjected to virtual screening to retrieve inhibitors. The compound SCHEMBL19100243 (PubChem CID- 76749591) displays a high affinity with the target protein. The affinity scores of this compound are more than known drugs. ADMET analysis and BOILED Egg plot provide insights into this compound as a potent inhibitor of JAK3.

Design of PD-L1 inhibitors for lung cancer.

The progression of lung cancer is associated with inactivation of programmed cell death protein 1, abbreviated as PD- 1 which regulates the suppression of the body's immune system by suppressing T- cell inflammatory activity and is responsible for preventing cancer cell growth. It is of interest to identify inhibitors for PD-L1 dimeric structure through molecular docking and virtual screening. The virtual screened compound XGIQBUNWFCCMAS-UHFFFAOYSA-N (PubChem CID: 127263272) displays a high affinity with the target protein. ADMET analysis and cytotoxicity studies further add weight to this compound as a potential inhibitor of PD-L1. The established compound BMS-202 still shows the high re-rank score, but the virtual screened drug possesses a better ADMET profile with a higher intestinal absorption value and lower toxicity.