Each item below is tagged by what was actually studied. Observed means data on Ac-LKKTETQ, LKKTETQ, or a stated TB-500 preparation. Proposed means an active-site assignment or extrapolation. Tβ4-only means the experiment used full-length thymosin β4 or a different fragment.
Observed
Heptapeptide identity
Confiscated TB-500 characterized as Ac-LKKTETQ, MW 888.4910 versus Tβ4 4963.4642. Equine plasma/urine detection after a 10 mg TB-500 administration in horses.
Esposito 2012, PMID 22962027; Ho 2012, PMID 23084823; FDA GSRS UNII QHK6Z47GTG.
Observed
7-aa motif, endothelium
The 7-amino-acid motif was necessary for HUVEC migration and chick aortic-arch sprouting at about 50 nM. Incomplete motifs were inactive.
Philp, Huff, Gho, Hannappel, Kleinman 2003, PMID 14500546.
Observed
LKKTETQ in aged mice
LKKTETQ matched Tβ4 dermal repair in 26-month-old mice. In the same paper, Tβ4 itself was used in db/db mice and rats.
Philp, Badamchian, Scheremeta, Nguyen, Goldstein, Kleinman 2003, PMID 12581423.
Observed
Parent vs metabolite screen
In a fibroblast wound screen, parent Ac-LKKTETQ was not significant. The metabolite Ac-LKKTE was. This undercuts casual claims that the intact heptapeptide is simply a more stable or more potent Tβ4.
Rahaman et al. 2024, PMID 38382158.
Proposed
17–23 active-site map
Sosne 2010 assigns angiogenesis, wound, and migration activities to LKKTETQ (17–23). That is a structure–function map inside Tβ4, not a demonstration that marketplace TB-500 reproduces the full Tβ4 phenotype.
Sosne, Qiu, Goldstein, Wheater 2010, PMID 20179146.
Tβ4-only
G-actin 1:1 binding
Tβ4 = Fx; 1:1 G-actin binding; inhibits polymerization. This is intact 43-aa protein biochemistry, not a TB-500 binding isotherm.
Safer, Elzinga, Nachmias 1991, PMID 1999398.
Tβ4-only
Ac-SDKP and 1–15
Anti-inflammatory / anti-fibrotic assignment sits on Ac-SDKP (1–4). Survival assignment sits on residues 1–15. Neither is the TB-500 sequence.
Sosne 2010, PMID 20179146.
Tβ4-only
Cardiac ILK / Akt
Mouse coronary-ligation work reporting integrin-linked kinase / Akt signaling used thymosin β4, not TB-500.
Bock-Marquette et al. 2004, PMID 15565145.
Tβ4-only
Human Tβ4 exposures
Opened human papers are intravenous or topical Tβ4 (Phase 1 IV; Phase 2 ulcer gel; topical RGN-259, n=9). None is an injectable TB-500 efficacy trial.
Ruff 2010, PMID 20536472; Treadwell 2012, PMID 23050815; Sosne 2015, PMID 25826322.