LSKL TFA (H-Leu-Ser-Lys-Leu-NH2 TFA) is a LAP-TGFβ derivative and a TGF-β1 antagonist that can cross the blood-brain barrier, inhibits the binding of TSP-1 to LAP and reduces renal interstitial fibrosis and liver fibrosis, inhibits subarachnoid fibrosis by inhibiting TSP-1-mediated TGF-β1 activity, prevents the occurrence of chronic hydrocephalus and improves long-term neurocognitive deficits after subarachnoid hemorrhage.

LSKL TFA from the latent form of TGF-β is responsible for the interaction with the KTFR sequence from ADAMTS1, leading to TGF-β activation. There is a stable binding mode between LSKL, Inhibitor of Thrombospondin (TSP-1) and ADAMTS1 KTFR sequence, characterized by 3 salt bridges and 2 hydrogen bonds. [3]

Intraperitoneal injection of 1 mg/kg LSKL TFA, into male rats exerted a protective effect against subarachnoid fibrosis, attenuated ventricular enlargement, and effectively inhibited the development of hydrocephalus. [1]
Intraperitoneal injection of 30 mg/kg LSKL TFA, was able to successfully inhibit the Smad signaling pathway activated by transforming growth factor-β (TGF-β) after partial hepatectomy. LSKL effectively attenuated the activation of TGF-β-Smad signaling by antagonizing TSP-1 rather than reducing TSP-1 protein expression. [2]