| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
TGF-β1[1]
LSKL targets thrombospondin-1 (TSP-1), a large homotrimeric matricellular glycoprotein that is a major physiological activator of latent TGF-β1. TSP-1 activates latent TGF-β1 through direct binding of its KRFK (Lys-Arg-Phe-Lys) sequence to a complementary LSKL sequence within the LAP of the latent TGF-β1 complex. LSKL exerts its inhibitory effect by acting as a decoy, competitively binding to the KRFK motif on TSP-1 and physically obstructing the interaction between TSP-1 and the latent TGF-β1 complex. This prevents the activation of TGF-β1, a critical mediator of fibrosis and cellular proliferation. |
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| ln Vitro |
The activation of TGF-β from its latent state is attributed to the interaction between the KTFR sequence from ADAMTS1 and the LSKL, Inhibitor of Thrombospondin (TSP-1) (LSKL peptide). Three salt bridges and two hydrogen bonds define a stable binding mechanism between the ADAMTS1 KTFR sequence and LSKL, an inhibitor of thrombospondin (TSP-1)[2].
In vitro, LSKL functions as a potent and specific competitive inhibitor of TSP-1's ability to activate latent TGF-β1. It competitively antagonizes the interaction between TSP-1 and the LAP of the TGF-β complex. LSKL alleviates renal interstitial fibrosis and hepatic fibrosis by antagonizing TSP-1. It is effective at picomolar concentrations in inhibiting TSP-1 binding to LAP. The compound does not affect TSP-1 protein expression but rather neutralizes its function in the TGF-β1 activation pathway. Its activity is assessed in cell-based assays measuring TGF-β signaling and fibrotic markers. |
| ln Vivo |
In male Sprague-Dawley rats, intraperitoneal administration of LSKL, Inhibitor of Thrombospondin (TSP-1) (1 mg/kg), attenuates ventriculomegaly, and effectively reduces hydrocephalus. The administration of LSKL, an inhibitor of thrombospondin (TSP-1), suppresses TGF-β1 activity and the ensuing Smad2/3 signaling[1]. ?LSKL, or Inhibitor of Thrombospondin (TSP-1) (30 mg/kg, ip), effectively prevents partial hepatectomy-induced activation of the transforming growth factor (TGF) β-Smad signal. Thrombospondin (TSP-1) inhibitor LSKL effectively inhibits TGF-β-Smad signal activation by opposing TSP-1, but not by lowering TSP-1 protein expression. Following a hepatectomy, hepatocyte proliferation is accelerated by LSKL, an inhibitor of thrombospondin (TSP-1)[3].
In vivo, LSKL has been shown to alleviate renal interstitial fibrosis and hepatic fibrosis. It successfully attenuates TGF-β-Smad signal activation by antagonizing TSP-1. The peptide has been investigated in models of fibrosis, where it reduces pathological TGF-β signaling and fibrotic tissue deposition. LSKL/NPs (nanoparticle formulations) have been designed to scavenge extracellular TSP-1, suppressing TSP-1-mediated oxidative stress signaling and attenuating endothelial and epithelial apoptosis. Further in vivo studies are needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for LSKL typically involve assessing its ability to inhibit the interaction between TSP-1 and the LAP of latent TGF-β1. Competitive binding assays using purified TSP-1 and LAP proteins are employed to measure the peptide's inhibitory activity. The peptide is effective at picomolar concentrations in inhibiting TSP-1 binding to LAP. Surface plasmon resonance (SPR) or ELISA-based binding assays can be used to quantify the interaction and determine inhibition constants. Assays are conducted in buffered solutions at physiological pH with appropriate protein preparations.
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| Cell Assay |
In vitro cell-based assays for LSKL utilize cell lines that respond to TGF-β signaling or produce fibrotic markers. Cells are treated with LSKL in the presence of TSP-1 to assess inhibition of TGF-β1 activation. TGF-β-Smad signal activation is measured by assessing Smad2/3 phosphorylation by Western blot or using Smad-responsive reporter gene assays. The expression of fibrotic markers such as α-SMA and fibronectin is measured by qPCR or immunofluorescence. Standard cell culture conditions (37°C, 5% CO₂) with appropriate media are employed.
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| Animal Protocol |
Animal/Disease Models: 103 male SD (Sprague-Dawley) rats (6 weeks of age; 160-180 g) with subarachnoid hemorrhage (SAH)[1]
Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Was protective against subarachnoid fibrosis, attenuated ventriculomegaly and effectively suppressed hydrocephalus. In vivo animal studies with LSKL typically involve administration of the peptide to rodent models of fibrosis, such as renal interstitial fibrosis or hepatic fibrosis models. The peptide is administered via appropriate routes (e.g., intravenous, intraperitoneal, or subcutaneous) at various doses. Endpoints include assessment of fibrotic tissue deposition, measurement of TGF-β signaling markers, evaluation of inflammatory markers, and histopathological analysis. LSKL/NPs have been used to scavenge extracellular TSP-1 in peripheral vessels in models of ischemia-reperfusion injury. All procedures must comply with institutional animal care and use guidelines. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for LSKL are not extensively documented in the publicly available literature. As a tetrapeptide, its oral bioavailability would be limited due to gastrointestinal degradation and poor permeability. The peptide is typically administered via parenteral routes for in vivo studies. Its molecular weight is approximately 487.6 g/mol (as the free peptide). The TFA salt form (CAS#: 2828433-17-4) is used to enhance solubility and stability. The compound is typically stored under conditions recommended for peptide research chemicals. Further studies are needed to characterize its pharmacokinetic profile.
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| Toxicity/Toxicokinetics |
LSKL is intended for research use only and is not approved for human therapeutic applications. As a research peptide, comprehensive toxicological data are not extensively documented in the publicly accessible literature. Standard safety precautions should be observed when handling this compound, including the use of appropriate personal protective equipment. As with all research chemicals, comprehensive toxicological profiling would be required before any consideration for clinical development. The compound should be handled in well-ventilated areas with proper waste disposal procedures.
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| References |
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| Additional Infomation |
LSKL, Inhibitor of Thrombospondin (TSP-1) (TFA) (CAS#: 2828433-17-4) is a synthetic tetrapeptide (Leu-Ser-Lys-Leu) derived from the latency-associated peptide (LAP) of TGF-β1. It functions as a potent and specific competitive inhibitor of TSP-1's ability to activate latent TGF-β1. LSKL alleviates renal interstitial fibrosis and hepatic fibrosis by antagonizing TSP-1, but not by reducing TSP-1 protein expression. It is effective at picomolar concentrations. This compound is not a drug and has not undergone clinical trials.
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| Molecular Formula |
C23H43F3N6O7
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|---|---|
| Molecular Weight |
572.62
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| Exact Mass |
572.314
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| CAS # |
2828433-17-4
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| Related CAS # |
LSKL, Inhibitor of Thrombospondin (TSP-1);283609-79-0
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| PubChem CID |
145707571
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
39
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| Complexity |
697
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| Defined Atom Stereocenter Count |
4
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| SMILES |
[C@@H](C(=O)N)(CC(C)C)NC(=O)[C@@H](NC([C@H](CO)NC(=O)[C@@H](N)CC(C)C)=O)CCCCN.OC(=O)C(F)(F)F
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| InChi Key |
FULCVSARTMWAGA-SITLLQIKSA-N
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| InChi Code |
InChI=1S/C21H42N6O5.C2HF3O2/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;3-2(4,5)1(6)7/h12-17,28H,5-11,22-23H2,1-4H3,(H2,24,29)(H,25,32)(H,26,31)(H,27,30);(H,6,7)/t14-,15-,16-,17-;/m0./s1
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| 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;2,2,2-trifluoroacetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 250 mg/mL (436.59 mM)
H2O: 100 mg/mL (174.64 mM） |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 100 mg/mL (174.64 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7464 mL | 8.7318 mL | 17.4636 mL | |
| 5 mM | 0.3493 mL | 1.7464 mL | 3.4927 mL | |
| 10 mM | 0.1746 mL | 0.8732 mL | 1.7464 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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