What is TB 500?

Thymosin

Thymosin is a hormone secreted from the thymus. This is the reason why it is named Thymosin. But most are now known to be present in many other tissues. Its primary function is to stimulate the production of T cells, which are an important part of the immune system. Thymosin also assists in the development of B cells to plasma cells to produce antibodies. It is classified as α, β and γ thymosins on the basis of their behaviour in an electric field. Thymosin has biological activities, and two in particular, thymosin α1 and thymosin β4, have potentially important uses in medicine, some of which have already progress from the laboratory to the clinic.

Beta thymosins

Thymosin β4 is also called TB-500. It is a protein that in humans is encoded by the TMSB4X gene. And it is a member of the beta thymosin group, of which there are 15 subtypes reported to date. Beta thymosins are a family of proteins which have in common a sequence of about 40 amino acids similar to the small protein thymosin β4. They are found almost exclusively in multicellular animals. Beta thymosins all possess the amino acid sequence 17-LKKTETQEK-25, which serves as an actin binding site.

The function of Thymosin β4

Thymosin β4 (TB-500) was initially isolated from the calf thymus in 1981. It is a small 43-amino acid intracellular peptide in most cell types representing approximately 70%–80% of the total thymosin content. It has a molecular weight of approximately 4.9 kDa. TB-500 can be found in most body cells and organs, with high concentrations present in blood platelets, neutrophils, and lymphoid cells. Previous studies have shown several key biological activities for TB-500 are to promote cell migration, angiogenesis and cell differentiation, prevent apoptosis, promote cell survival, and tissue regeneration in vitro and in vivo. Such properties have provided the scientific rationale for a number of ongoing and planned clinical trials. TB-500 would serve as a topical treatment in wound repair and regeneration both on the skin and in the eyes, considerable inflammation induced by burning injury, pressure ulcer, tumor suppression in colorectal cancer and neurological functional recovery.

Recent studies have suggested that TB-500 is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. The shRNA knockdown of TB-500 results in significant cardiac development defects. The cardiac regeneration potential of neonatal mice could be extended to the 7th post-natal day by TB-500. Treatment with TB-500 prior to myocardial infarction can promote cardiomyocyte formation. It has been reported that TB-500 can activate quiescent adult epicardial cells (EPDCs) to sustain and repair the myocardium after ischemic damage. This favors the efficient cardiac regeneration post-infarction (MI) required for the replacement of lost cardiomyocytes. However, insight into how to stimulate repair of human heart is currently limited.

References:

Lee, Jun Yeon, et al. "Synthesis and biological screening of small molecule peptides based on the amino acid sequence of thymosin β4." Journal of the Korean Society for Applied Biological Chemistry 58.5 (2015): 651-658.

Nie, Li, et al. "Thymosin β4 impeded murine stem cell proliferation with an intact cardiovascular differentiation." Journal of Huazhong University of Science and Technology [Medical Sciences] 36.3 (2016): 328-334.