TB-500

TB-500
Full Name Thymosin Beta-4 Fragment
Also Known As Tβ4, Thymosin β4
Type Synthetic Peptide
Amino Acids 43 (full Tβ4)
Active Region Ac-LKKTETQ (17-mer)
Molecular Weight 4,963 Da (Tβ4)
Status Research compound
Origin Naturally occurring in thymus and many cell types

TB-500 is a synthetic version of thymosin beta-4 (Tβ4), a 43-amino acid peptide that occurs naturally in virtually all human and animal cells. Thymosin beta-4 was originally isolated from the thymus gland and is involved in numerous cellular processes including wound healing, cell migration, and tissue repair.

Discovery and Background

Thymosin beta-4 was first isolated from calf thymus in 1981 by Allan Goldstein and colleagues. It belongs to a family of highly conserved polar peptides called beta-thymosins. TB-500 is the synthetic form commonly used in research settings.

The protein was initially thought to be primarily a thymic hormone but was later found to be present in virtually all cell types, where it plays important roles in actin regulation and cellular motility.

Chemical Structure

Thymosin beta-4 is a small, highly conserved peptide consisting of 43 amino acids. Its primary function involves binding to and sequestering G-actin (monomeric actin), thereby regulating actin polymerization in cells.

Amino Acid Sequence

The full amino acid sequence of human thymosin beta-4 is:

Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES

Active Region

The active region responsible for many of TB-500's effects is believed to be the central 17-amino acid actin-binding domain: LKKTETQ. This sequence is critical for the peptide's interaction with actin and its biological activities.

Mechanism of Action

TB-500/Thymosin beta-4 exerts its effects through several mechanisms:

Actin Regulation

The primary biochemical function of thymosin beta-4 is the sequestration of G-actin:

  • Binds to G-actin with a 1:1 stoichiometry
  • Prevents premature actin polymerization
  • Maintains a pool of actin monomers for rapid polymerization when needed
  • Promotes cell migration by regulating cytoskeletal dynamics

Cell Migration

By regulating actin dynamics, TB-500 promotes cell migration, which is essential for:

  • Wound healing
  • Blood vessel formation (angiogenesis)
  • Stem cell recruitment to injury sites

Anti-Inflammatory Effects

Research suggests thymosin beta-4 may have anti-inflammatory properties through:

  • Modulation of inflammatory cytokine expression
  • Reduction of oxidative stress
  • Interaction with NF-κB pathways

Research Applications

TB-500 has been studied in various preclinical and some clinical contexts:

Wound Healing

Multiple studies have examined TB-500's effects on wound healing:

  • Dermal wound repair in rodent models
  • Corneal wound healing studies
  • Enhanced keratinocyte and endothelial cell migration

Cardiac Research

Some of the most promising research has involved cardiac tissue:

  • Post-myocardial infarction recovery in animal models
  • Promotion of cardiac progenitor cell migration
  • Potential effects on cardiac remodeling

Musculoskeletal Research

Studies have investigated effects on:

  • Muscle fiber regeneration
  • Tendon repair models
  • Ligament healing

Neurological Research

Emerging research has explored potential neuroprotective effects:

  • Central nervous system injury models
  • Multiple sclerosis research
  • Peripheral nerve regeneration
Clinical Development: Thymosin beta-4 (under the name RGN-352) has undergone clinical trials for certain applications, including dry eye syndrome and pressure ulcers. However, it remains investigational for most applications.

TB-500 vs BPC-157

TB-500 and BPC-157 are both research peptides studied for tissue healing, but they differ in several ways:

Characteristic TB-500 BPC-157
Origin Thymus gland / ubiquitous Gastric juice protein
Size 43 amino acids 15 amino acids
Primary Mechanism Actin regulation Growth factor modulation
Systemic Effects More systemic More localized
Research Dosing Milligram range Microgram range

Administration in Research

In research protocols, TB-500 has been administered via:

  • Subcutaneous injection: Most common route in research
  • Intramuscular injection: Used in some protocols
  • Topical application: For wound healing studies

Research Dosing

Research protocols have used various dosing strategies, often including:

  • Loading phases with higher initial doses
  • Maintenance phases with reduced frequency
  • Typical ranges of 2-5mg per administration in research settings
Research Status: TB-500 is a research compound. While some formulations of thymosin beta-4 have undergone clinical trials, TB-500 itself is not approved for human therapeutic use.

Safety Considerations

In preclinical studies, thymosin beta-4 has generally shown a favorable safety profile. However:

  • Long-term human safety data is limited
  • Potential effects on cancer cell migration have been investigated (with conflicting results)
  • As with any research compound, unknown risks may exist

References

  1. Goldstein AL, et al. "Thymosin beta 4: a multi-functional regenerative peptide." Expert Opin Biol Ther. 2012.
  2. Smart N, et al. "Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization." Nature. 2007.
  3. Philp D, et al. "Thymosin beta 4 promotes angiogenesis, wound healing, and hair follicle development." Mech Ageing Dev. 2004.
  4. Crockford D, et al. "Thymosin beta 4: Structure, function and biological properties supporting clinical applications." Ann N Y Acad Sci. 2010.