Thymosin Beta-4 Sulfoxide (TB4-SO)

Also known as: Thymosin Beta-4 Sulfoxide, TB4-S, Oxidized TB4

Immune SupportHealing & RecoveryAnti-Aging & Longevity

Overview

Thymosin beta-4 sulfoxide (TB4-SO) is the naturally occurring oxidized form of Thymosin Beta-4 generated by methionine-6 oxidation. Unlike the reduced parent compound, TB4-SO does not bind G-actin and thus lacks TB-500's actin-sequestering activity. Instead, TB4-SO has potent and specific anti-inflammatory properties independent of G-actin binding—activating the Nrf2 transcription factor pathway to upregulate antioxidant and anti-inflammatory gene expression. TB4-SO is considered an important endogenous immunomodulatory signal in inflammatory conditions where ROS-mediated oxidation of TB4 occurs.

Mechanism of Action

TB4-SO specifically interacts with Kelch-like ECH-associated protein 1 (KEAP1), the E3 ubiquitin ligase that normally targets Nrf2 for proteasomal degradation. By binding KEAP1, TB4-SO displaces Nrf2 from the KEAP1-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and activate antioxidant response elements (AREs). This drives expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), glutamate-cysteine ligase, and other cytoprotective enzymes. This mechanism is mechanistically distinct from TB4's G-actin binding and operates independently at sites of oxidative stress.

Potential Benefits

  • Anti-inflammatory activity via Nrf2 pathway activation
  • HO-1 upregulation with potent cytoprotective effects
  • Antioxidant gene expression induction
  • Endogenous anti-inflammatory signal generated under oxidative stress
  • Potential in inflammatory bowel disease and oxidative stress conditions

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

Not separately administered; generated endogenously from TB4 at inflammatory sites.

Amino Acid Sequence

Ac-Ser-Asp-Lys-Pro-Asp-Met(O)-Ala-Glu-Ile-Glu-Lys-Phe-Asp-Lys-Ser-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-Pro-Leu-Pro-Ser-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-Ala-Gly-Glu-Ser (Met6 → Met6-sulfoxide)

Side Effects & Safety

  • Not independently characterized; see TB-500 entry

Synergistic Compounds

The following compounds have been studied alongside Thymosin Beta-4 Sulfoxide (TB4-SO) for potential complementary or synergistic effects:

TB-500 (Thymosin Beta-4)Sulforaphane (Nrf2 activator)NAC

Learn More

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References & Further Reading

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