Background of Drug Discovery Targeting Lysosomal mTOR Signaling
The target of rapamycin protein (mTOR) is an evolutionarily conserved serine/threonine kinase that has critical roles in diverse biological processes, such as cell proliferation, survival, autophagy, metabolism , and immunity. In cells, mTOR exists as two structurally distinct complexes, called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), each specific to a different subset of effectors. mTORC1 localisation in the lysosome is essential for its ability to sense and respond to changes in amino acid levels. mTORC2 is not only regulated by growth factors, but also activates type I insulin-like growth factor receptor (IGF-IR) and insulin receptor (InsR) through the tyrosine kinase activity of mTOR. Besides, mTORC2 regulates the actin polarization and endocytosis. The de-regulated activity of mTOR is involved in many pathophysiological conditions, such as aging, Alzheimer 's disease, diabetes, obesity, and cancer.
Fig. 1. mTORC1 regulates lysosomal function in normal and starvation conditions. (Puertollano R, 2014)
Solutions
mTOR activity is frequently dysregulated in many human cancers, such as breast, prostate, lung, liver and kidney cancers. mTOR signalling upregulation can promote tumour growth and progression through a variety of mechanisms, including promotion of growth factor receptor signaling, angiogenesis, glycolytic metabolism, lipid metabolism, cancer cell migration and inhibition of autophagy. Our scientists have identified lysosomal mTOR as a highly relevant target for therapeutic intervention in cancer to develop appropriate targeting measures. Our goal is to help you design mTOR inhibitors to reduce mTOR activity in cancer cells.
In collaboration with international cytologists, CD BioSciences is committed to providing our global customers with strategies to target lysosomal mTOR signaling in cancer. We offer a wide range of lysosomal mTOR targets.
Targeting mTORC1
S6K1, 4E-BP1, FIIIC, Maf1, RNA polymerase 1/2/3, SKP2, etc.
Targeting mTORC2
Protein kinase C (PKC) α/β, SGK, Akt, IGF2 mRNA binding protein, insulin receptor, ser/thr kinase.
Based on the large number of potential targets we have developed for mTOR in cancer cells, we are also focusing on drug design with selective inhibitor potential and specificity. We seek to design known compounds against the upstream regulators and downstream targets of mTORC associated with cancer as described above. Our services support the pre-clinical studies of these compounds.
- Rapamycin analogues.
- ATP-competitive mTOR inhibitors.
- Dual PI3K/mTOR inhibitors.
Why Choose Us
- Theoretical support for mTOR in yeast and mTOR in mammals.
- A multi-targeting strategy for lysosomal mTOR in cancer.
- Rapid experimental process to deliver results at an economical cost.
- Collaborate with experienced international technical staff.
CD BioSciences can meet any reasonable needs of our clients, taking time and budget into consideration for you. Our aim is to be customer-centric and to provide the highest quality services to customers. Our customer service representatives are enthusiastic and trustworthy 24 hours a day, 7 days a week. If you are interested in our services, please feel free to contact us for more information or a detailed discussion.
Reference
- Puertollano R. (2014) mTOR and lysosome regulation. F1000Prime Rep. 6:52.