LSKL, Inhibitor of Thrombospondin (TSP-1)

LSKL, Inhibitor of Thrombospondin (TSP-1) is a latency-associated protein (LAP)-TGFβ derived tetrapeptide and a competitive TGF-β1 antagonist. LSKL, Inhibitor of Thrombospondin (TSP-1) inhibits the binding of TSP-1 to LAP and alleviates renal interstitial fibrosis and hepatic fibrosis. LSKL, Inhibitor of Thrombospondin (TSP-1) suppresses subarachnoid fibrosis via inhibition of TSP-1-mediated TGF-β1 activity, prevents the development of chronic hydrocephalus and improves long-term neurocognitive defects following subarachnoid hemorrhage (SAH). LSKL, Inhibitor of Thrombospondin (TSP-1) can readily crosse the blood-brain barrier.

Product information

CAS Number: 283609-79-0

Molecular Weight: 458.60

Formula: C21H42N6O5

Chemical Name: (2S)-6-amino-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanamide

Smiles: CC(C)CC(NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(N)CC(C)C)C(N)=O

InChiKey: YOKXDNNIFSAXBY-UHFFFAOYSA-N

InChi: InChI=1S/C21H42N6O5/c1-12(2)9-14(23)19(30)27-17(11-28)21(32)25-15(7-5-6-8-22)20(31)26-16(18(24)29)10-13(3)4/h12-17,28H,5-11,22-23H2,1-4H3,(H2,24,29)(H,25,32)(H,26,31)(H,27,30)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 100 mg/mL (218.05 mM). H2O : 50 mg/mL (109.03 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

The KTFR sequence from ADAMTS1 is responsible for the interaction with the LSKL, Inhibitor of Thrombospondin (TSP-1) (LSKL peptide) from the latent form of TGF-β, leading to its 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.

In Vivo:

LSKL, Inhibitor of Thrombospondin (TSP-1) (1 mg/kg; intraperitoneal injection; male Sprague-Dawley rats) is protective against subarachnoid fibrosis, attenuates ventriculomegaly and effectively suppresses hydrocephalus. LSKL, Inhibitor of Thrombospondin (TSP-1) treatment inhibits TGF-β1 activity and subsequent Smad2/3 signaling. LSKL, Inhibitor of Thrombospondin (TSP-1) (30 mg/kg, i.p.) successfully inhibits transforming growth factor (TGF) β-Smad signal activation induced by partial hepatectomy. LSKL, Inhibitor of Thrombospondin (TSP-1) successfully attenuates TGF-β-Smad signal activation by antagonizing TSP-1, but not by reducing TSP-1 protein expression. LSKL, Inhibitor of Thrombospondin (TSP-1) accelerates hepatocyte proliferation after hepatectomy.

References:

1. Liao F, et al. LSKL peptide alleviates subarachnoid fibrosis and hydrocephalus by inhibiting TSP1-mediated TGF-β1 signaling activity following subarachnoid hemorrhage in rats. Exp Ther Med. 2016 Oct;12(4):2537-2543. Epub 2016 Aug 31.
2. Laurent MA, et al. In silico characterization of the interaction between LSKL peptide, a LAP-TGF-beta derived peptide, and ADAMTS1. Comput Biol Chem. 2016 Apr;61:155-61.
3. Kuroki H, et al. Effect of LSKL peptide on thrombospondin 1-mediated transforming growth factor β signal activation and liver regeneration after hepatectomy in an experimental model. Br J Surg. 2015 Jun;102(7):813-25.

Products are for research use only. Not for human use.