What is proteasome?
The proteasome is an essential part of cellular homeostasis, regulating essential functions such as cell cycle control, immune regulation, apoptosis transcription, protein homeostasis, and synaptic plasticity
The proteasome is the cell’s garbage processing facility that degrades expired or mis-folded proteins
Cancer cells and autoimmune cells produce “many” proteins, making them much more sensitive to proteasome inhibition
Hematologic
malignancies
Solid tumors
Inflammation &
Autoimmune disease
The proteasome is an ideal drug target for diseases in which cells overproduce proteins, such as cancer and autoimmune diseases
Proteasome and Diseases
Oncology
Hematologic malignancies
Multiple Myeloma is a cancer of plasma cells that produce a large amounts of monoclonal proteins such as immunoglobulins. Multiple Myeloma is one of the tumors sensitive to proteasome inhibition at low concentration. So far, it is the only indication for first-generation proteasome inhibitors due to its low therapeutic window
Solid tumors
The functions of the proteasome overlap in solid tumors and hematological malignancies. Although the sensitivity of proteasome inhibition in solid tumors is presumed to be lower than that of hematologic malignancies, the ability of the proteasome to handle oxidative and toxic stress may support a rational basis for proteasome inhibitors as novel therapies in solid tumors
Proteasome
Immunology
Inflammation & Autoimmune disease
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease and myasthenia Gravis (MG) is an organ-specific autoimmune disease. These autoimmune diseases are driven by autoantibodies to various nuclear or cytoplasmic proteins. These diseases can be addressed by eliminating IgG overproducing cells with proteasome inhibitors<
QLi5 compounds can be used with higher and more frequent dosing regimens, making them useful for a wider range of indications
Technologies
- The proteasome is a multi-subunit protein complex with a very complicated structure
- The three-dimensional structures of constitutive proteasome and immunoproteasome was solved in the world’s first in Professor Huber’s laboratory
- Solid structural understanding enables novel chemical series of proteasome inhibitors with broad selectivity
Scientific publications
Abstract 416: A novel non-covalent and rapidly reversible proteasome inhibitor for multiple myeloma and various solid cancers
American Association for Cancer Research (AACR) 2022
Proteasome as a drug target
Proteasome is an essential part of cellular homeostasis that regulates essential functions such as cell cycle control, immune regulation, apoptosis transcription, proteostasis and synaptic plasticity
If proteins don’t disappear at the right time, it causes a lot of troubles
QLi5
Targeting wide spectrum of proteasome indications with wide spectrum compounds
