TB-500 FRAG 1-4 (Ac-SDKP)

TB-500 FRAG 1-4 is the product name for Ac-SDKP, in full N-acetyl-seryl-aspartyl-lysyl-proline. These are the first four amino acids of thymosin beta-4 (Tβ4), the 43-residue protein known as TB-500. At roughly 487 daltons it is one of the smallest peptides in the range. Unlike TB-500 FRAG, Ac-SDKP does not come from inside the protein but is its very beginning: enzymes such as prolyl oligopeptidase clip it off Tβ4 in the body, so it circulates naturally in the blood, although only at nanomolar levels (around 2 to 3 nmol/l in healthy people).

It was isolated and its structure determined in 1989 by a French group around Lenfant, who were searching fetal calf bone marrow for a substance that keeps blood-forming stem cells quiescent. In the 1990s this became the drug candidate goralatide (also seraspenide), meant to spare the bone marrow of cancer patients during chemotherapy. Only later did animal models show that the peptide curbs the build-up of connective tissue in heart, kidney and lung, pushes back inflammatory cells and stimulates the growth of new blood vessels. Today it is studied mainly as an endogenous antifibrotic factor.

One distinction matters: TB-500 FRAG in the range stands for a different piece of Tβ4, the actin-binding region further inside the protein. Ac-SDKP does not bind actin and works through other pathways. It is therefore not a more compact TB-500 but a molecule of its own with its own research history. For the isolated peptide there is no established protocol in humans.

This information is for research and educational purposes only. No medical advice.

In the body Ac-SDKP is tightly linked to angiotensin-converting enzyme (ACE). ACE cleaves the tetrapeptide through its N-domain and thereby keeps the level permanently low. Anyone taking an ACE inhibitor has four to five times more Ac-SDKP in the blood: in a Paris study a single dose of captopril raised the level in healthy subjects 5.5-fold (Azizi and colleagues 1996). Part of the tissue-protective effect of ACE inhibitors is attributed in the research to exactly this rise.

At the tissue level Ac-SDKP acts on three fronts. First, it restrains fibroblasts: it inhibits their proliferation and collagen production and blocks their conversion into myofibroblasts, which the growth factor TGF-beta would otherwise trigger, probably via the Smad2 and ERK1/2 signalling pathways. Second, it dampens inflammation, with fewer macrophages infiltrating the tissue in animal models. Third, it stimulates endothelial cells to divide, migrate and form tubes, the basic steps of new vessel growth. In the rat studies it left blood pressure and heart size unchanged.

The original function remains: Ac-SDKP reversibly keeps blood-forming stem cells from entering the division phase. That was the reason to test it as protection during chemotherapy. It is at the same time the effect to keep in mind with any use.

Ac-SDKP is supplied as a powder like other peptides and dissolved before use. You need the same basic kit as for TB-500.

• The TB-500 FRAG 1-4 vial with 10 mg of lyophilised powder.
• Bacteriostatic water for reconstitution.
• U-100 insulin syringes.
• Alcohol swabs for the vial cap and the skin.
• A sealable container for used needles.

Because there is no established protocol, a notebook is worth adding: date, amount, observations. That is the only way to say anything about your own tolerability at the end.

The powder is dissolved with bacteriostatic water. The amount of water sets the concentration and with it how many units on a U-100 syringe correspond to a given amount. The calculator above shows the concentration for the 10 mg vial at each water volume; it deliberately shows no dose steps for this product.

For orientation: 10 mg in 2 ml gives 5 mg per ml, so 10 units on the U-100 syringe then hold 0.5 mg. With 1 ml the solution is twice as concentrated, with 3 ml correspondingly thinner. Small volumes are no problem for a molecule this small, it dissolves readily.

Simply add the water to the vial, it can go in quickly. Then swirl or shake until everything has dissolved, both are fine. If the solution turns gel-like or lumpy, do not use the vial; slight cloudiness on its own is no reason to discard it.

Where Ac-SDKP has been administered in research at all, it ran subcutaneously or intraperitoneally as a continuous infusion in animals, in humans as a 12- to 48-hour infusion and, in the kinetics study, also as a single subcutaneous or intramuscular injection, with complete absorption under the skin (Ezan and colleagues 1994). For a single subcutaneous shot the standard technique applies: clean the skin with an alcohol swab, let it dry briefly, pinch a skin fold and insert the needle at 45 to 90 degrees.

Inject slowly, wait a moment, withdraw the needle and drop it straight into the sharps container. Rotate injection sites, the abdomen and thighs are the usual zones.

Because the effect is meant to be systemic, proximity to a particular spot plays no role. Redness or a feeling of pressure at the injection site are the most common observations with small peptides and usually settle on their own.

The data are broad but almost entirely preclinical. In rats with aldosterone-salt hypertension a six-week infusion of 800 mcg/kg/day largely prevented fibrosis in heart and kidney without affecting blood pressure or organ size (Peng and colleagues 2001). After a heart attack Ac-SDKP reversed existing fibrosis and inflammation in the non-infarcted muscle of rats, but did not improve pump function and even worsened it in the prevention arm (Yang and colleagues 2004). Less scar tissue, in other words, does not automatically mean a better heart.

In cultured human cardiac fibroblasts the peptide suppressed the TGF-beta-driven conversion into myofibroblasts along with collagen production (Peng and colleagues 2010). In vascular models it promoted proliferation, migration and tube formation of endothelial cells, new vessel growth in the cornea around an implanted tumour cell spheroid and capillary density in the infarcted heart (Wang and colleagues 2004). For the diabetic kidney a Japanese group describes protection through inhibition of the conversion of endothelial cells into connective tissue cells (Kanasaki 2020). For the lung there are Chinese data on silica-induced fibrosis.

In humans the peptide itself is only thinly documented. A kinetics study in six healthy volunteers and five chemotherapy patients (Ezan and colleagues 1994) showed baseline levels of 1.7 to 3.2 nmol/l, a half-life of 4.5 minutes after the end of infusion and complete absorption after subcutaneous injection; nothing beyond kinetics was measured there. Captopril raised the level in healthy subjects 5.5-fold (Azizi and colleagues 1996). As seraspenide it protected blood cells during chemotherapy in a double-blind crossover study of 53 cancer patients without toxicity of its own (Carde and colleagues 1992). The larger placebo-controlled trial of 84 patients, however, did not reproduce that protection. Anaemia and lymphopenia were even more frequent under goralatide (Cappelaere and colleagues 1995). There are no clinical trials testing Ac-SDKP itself against fibrosis or for regeneration so far. None is listed in the ClinicalTrials.gov registry either. The reviews (Cavasin 2006, Kumar and Yin 2018) base the clinical side on the raised levels under ACE inhibitors.

Ac-SDKP is endogenous and showed no detectable toxicity in the hospital trial of 53 cancer patients. Tolerability was described as excellent in the placebo-controlled trial of 84 patients. In the animal studies over weeks no conspicuous adverse effects stood out, blood pressure and heart size stayed unchanged. The safety profile of subcutaneous self-use in milligram amounts, by contrast, has not been studied.

• Local reactions at the injection site such as redness, pressure or mild irritation.
• The core effect on blood-forming stem cells: in mice granulocytes fell during administration. Blood cells surged afterwards (Bogden and colleagues 1998). In the placebo-controlled cancer trial anaemia and lymphopenia were more frequent under goralatide (Cappelaere and colleagues 1995). An influence on the blood count is therefore not a theoretical construct.
• New vessel growth is a growth signal. In a rat model Ac-SDKP enhanced new vessel growth around implanted tumour cells (Wang and colleagues 2004). With pre-existing growths or tumour disease this has to be viewed critically. Human data are lacking.
• In one rat study after infarction systolic pump performance worsened under Ac-SDKP in the prevention arm and stayed unchanged in the reversal arm (Yang and colleagues 2004). What that means for humans is unclear.
• With ACE inhibitors the dose adds to a level that is already four to five times elevated.
• Solid long-term data on self-use are missing entirely.

Before mixing the powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. After mixing, keep it in the fridge (2 to 8 degrees), do not freeze. It stays good there for several months with barely any loss of potency.

Swirl or shake to mix, both are fine. A small tetrapeptide like this is chemically uncomplicated, but the usual rule for any solution still applies: work cleanly, disinfect the cap before every draw and note the mixing date on the vial.