: The ubiquitin proteasome system (UPS) is a crucial protein degradation pathway that involves several enzymes to maintain cellular protein homeostasis. This system has emerged as a major drug target against certain types of cancer as a disruption at the cellular level of UPS enzyme components forces the transformation of normal cell into cancerous cell. Although enormous advancements have been achieved in the understanding of tumorigenesis, efficient cancer therapy remains a goal towards alleviating this serious health issue. Since UPS has become a promising target for anticancer therapies, herein we provide comprehensive review of the ubiquitin proteasome system as a significant process for protein degradation. Herein, the anti-cancer therapeutic potential of this pathway is also discussed.

Envenomation resulting from snakebite is an important public health problem particularly in rural areas of Africa, Asia, and Latin America. Phospholipase A 2 and metalloprotease are some of the principal toxic components of snake venom. Hence, the inhibition of these enzymes is of pharmacological and therapeutic interest as they are involved in several hemorrhage and inflammatory diseases. This study employed in silico methods to provide insights into the inhibitory mechanism of 2',4'-dihydroxy-4-prenyloxychalcone and 3,5-dimethoxy-4'-O-(2,3dihydroxy-3-methylbutyl)-dihydrostilbene isolated from the aerial parts of I. conferta on PLA 2 and metalloprotease snake venom. The method includes; predicting their ADME properties, molecular docking, molecular dynamics simulation, and binding free energy calculations. The result of the MD simulation revealed the average RMSD values for the C-α backbone atoms of PLA 2 in complex with the prenylated chalcone and the prenylated stilbene to be 1.14 and 1.16 Ǻ while that of metalloprotease in complex with prenylated chalcone and the prenylated stilbene were 1.37 and 1.18Å. Also, the electrostatic forces and van der Waals forces made a greater contribution to the total binding free energy in the PLA 2 complexes than in the metalloprotease complexes implying that the compounds exerted a greater inhibitory effect on the PLA 2 than on the Metalloprotease. The design of specific inhibitors of PLA 2 could help in the development of new pharmaceutical drugs, more specific antivenom, or even as alternative approaches for treating snakebites