TB-500 (Thymosin Beta 4)

Tβ4, and thus TB-500, is thought to potentially increase the levels of microRNA-146a (miR-146a), which might function as a suppressive regulator of specific cellular signaling pathways, particularly those associated with inflammation-related cytokines, including L-1 receptor-linked kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6). The authors observed that "transfection of anti-miR-146a nucleotides reversed the inhibitory effect of Tβ4 on IRAK1 and TRAF6," suggesting this as a potential anti-inflammatory mechanism for TB-500.

In 1999, a research study was conducted on wounded murine test models who were introduced to TB-500 as a form of synthetic Thymosin Beta 4. Four days after the presentation, it was reported that the TB-500 peptide rats exhibited an apparent 41% increase in re-epithelialization than control murine models presented with saline. Seven days after the study, the TB-500 wounds were reported to be contracted by at least 11% more than the saline wounds. The authors commented that their observations "suggest that Tβ4 is a potent wound healing factor with multiple activities."

Research studies were carried out on normal rats and mice, diabetic mice, aged mice, and steroid-influenced rats. All these animals were served full-thickness punch wounds and introduced to the TB-500 peptide. It was reported that TB-500 appeared to accelerate the wound-healing process in all test models, regardless of pre-existing conditions. Furthermore, phase 2 clinical trials conducted on models of stasis and pressure ulcers reported that TB-500 might accelerate the healing process by as much as one month.

Pulmonary hypertension is considered a progressive cardiac disease where the pulmonary arteries restrict blood ejection by the right ventricle. It was reported by researchers that TB-500 might be action specific on the Notch3-Col 3A-CTGF gene axis in MCT-influenced mice, which appeared to result in decreasing the right ventricular heart cell hypertrophy by a significant amount. Based on Tβ4 research, TB-500 might also influence the regeneration of cardiac cells, enhance the resilience of myocardial cells under hypoxic conditions, and promote angiogenesis.

In 2003, studies were carried out on mice to examine the potential of TB-500 in hair growth. Under the influence of the TB-500 peptide, it was reported that via histological examination of the mouse skin cells, the peptide appeared to increase the number of hair shafts and hair follicles, thereby inducing hair growth. Upon real-time PCR and western blotting techniques, the m-RNA and protein levels were reported elevated in TB-500 mice, which might have significantly induced hair growth.

It is hypothesized that TB-500 might influence angiogenesis via several molecular interactions, based on studies involving TB-500 overexpression lentiviral vector in transfecting umbilical vein endothelial cells (HUVEC) and murine critical limb ischemia (CLI) models. Preliminary findings indicate that TB-500 might enhance not only the viability, angiogenesis, and migration of HUVEC but could also elevate the expression of angiopoietin-2 (Ang2), TEK receptor tyrosine kinase 2 (tie2), vascular endothelial growth factor A (VEGFA), NOTCH1 intracellular domain (N1ICD), Notch3, NF-κB, and phosphorylated p-p65 in these cells.

Studies have posited that TB-500 may modulate cytokine production and thus accelerate healing in corneal wound models. Following injury, some indication suggests that TB-500 could promote increased expression of IL-1β and IL-6 mRNA in the corneas of murine models. Moreover, TB-500 experimentation after alkali injury might lead to a decrease in the expression of chemoattractants such as MIP-2 and KC for polymorphonuclear neutrophils (PMNs), potentially resulting in diminished PMN infiltration.