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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
FSLLRY-NH2 specifically targets and inhibits the Protease-Activated Receptor 2 (PAR2), which is a G-protein coupled receptor (GPCR). PAR2 is typically activated by serine proteases like trypsin, tryptase, and coagulation factors. FSLLRY-NH2 acts as an antagonist, preventing the receptor from being activated by these endogenous proteases or by synthetic activating peptides.
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| ln Vitro |
FSLLRY-NH2 acts as a selective PAR2 antagonist. In vitro, it is reported to block PAR2 activation, thereby suppressing ERK activation and inhibiting collagen production in isolated cardiac fibroblasts. This demonstrates its efficacy in blocking fibrotic cellular pathways. The specific IC50 for receptor binding is not defined.
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| ln Vivo |
Following asphyxial CA (asphyxial brain injury), treatment with FSLLRY-NH2 (50 μg per rat given intranasally at 1 hour postresuscitation) dramatically improves neurological outcome and decreases the amount of degenerating hippocampus neurons[1].
In vivo, FSLLRY-NH2 reverses taxol-induced mechanical allodynia and heat hyperalgesia in ICR mice. It also blocks PKC activation in these pain models. Additionally, in a model of asphyxia-induced brain injury, treatment with FSLLRY-NH2 (50 microg per rat given intranasally at 1 hour post-resuscitation) significantly improves neurological outcomes and reduces the number of degenerating hippocampal neurons. |
| Enzyme Assay |
The specific protocol for in vitro receptor binding would use a competition binding assay. Membranes from cells expressing human PAR2 are prepared. Since the orthosteric site of PAR2 is a large binding groove, radiolabeled small molecule antagonists are typically used as tracers. FSLLRY-NH2 is incubated with the membranes and a fixed concentration of radiolabeled high-affinity PAR2 antagonist. After filtration, the IC50 is calculated. Alternatively, binding can be inferred via functional assays.
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| Cell Assay |
In a typical in vitro functional assay, HEK-293 cells stably transfected with PAR2 are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4 AM). Cells are pre-incubated with FSLLRY-NH2 (e.g., 10-300 microM) for 10-15 minutes. The PAR2 agonist trypsin (10 nM) or SLIGKV-NH2 (100 microM) is then added. The intracellular calcium flux is measured as an increase in fluorescence. The ability of FSLLRY-NH2 to reduce the calcium peak amplitude is measured, and IC50 values for inhibition are determined from concentration-response curves.
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| Animal Protocol |
For a pain model (Taxol-induced allodynia), female ICR mice are administered paclitaxel (Taxol) intraperitoneally on days 1, 3, 5, and 7 to induce neuropathic pain. On day 14, FSLLRY-NH2 is administered intrathecally (into the spinal cord) at doses of 10-100 nmol/mouse. Mechanical allodynia is assessed using von Frey filaments by measuring the paw withdrawal threshold at 0, 30, 60, 90, and 120 minutes post-injection. Heat hyperalgesia is assessed using a radiant heat source (Hargreaves apparatus). Reversal of allodynia indicates target engagement.
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| ADME/Pharmacokinetics |
As a peptide, FSLLRY-NH2 is expected to have low oral bioavailability and a short plasma half-life due to rapid proteolytic degradation. It is typically administered locally (intrathecally, intranasally) to maximize local target concentration. Detailed PK parameters (T1/2, Cl) are not available in standard databases. Its peptide nature limits systemic exposure.
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| Toxicity/Toxicokinetics |
Specific toxicology data for FSLLRY-NH2 has not been published. As a research peptide, its safety profile is not required for FDA submission. Peptide antagonists generally have lower toxicity than small molecules due to their high specificity and low accumulation in tissues. Standard in vitro cytotoxicity assays (MTT) on neuronal cell lines would be used to screen for safety prior to in vivo studies.
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| References | |
| Additional Infomation |
FSLLRY-NH2 is a widely-used research tool for studying PAR2 biology. It is not an FDA-approved drug. It is primarily employed in the fields of pain research (to block PAR2-dependent hyperalgesia), cancer research (to block PAR2-driven metastasis), and inflammation. It is often used in combination with activating peptides to confirm the specificity of observed effects. The amidated C-terminus improves resistance to carboxypeptidase digestion.
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| Molecular Formula |
C39H60N10O8
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|---|---|
| Molecular Weight |
796.955900000001
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| Exact Mass |
796.459
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| CAS # |
245329-02-6
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| Related CAS # |
FSLLRY-NH2 TFA
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| PubChem CID |
73352412
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.626
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| LogP |
0.6
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| Hydrogen Bond Donor Count |
11
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
57
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| Complexity |
1330
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC(C[C@H](NC([C@@H](NC([C@@H](NC([C@@H](N)CC1=CC=CC=C1)=O)CO)=O)CC(C)C)=O)C(N[C@H](C(N[C@H](C(N)=O)CC2=CC=C(O)C=C2)=O)CCCNC(N)=N)=O)C
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| InChi Key |
KMSCNWHRNILNRJ-JNRWAQIZSA-N
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| InChi Code |
InChI=1S/C39H60N10O8/c1-22(2)17-30(36(55)45-28(11-8-16-44-39(42)43)35(54)46-29(33(41)52)20-25-12-14-26(51)15-13-25)47-37(56)31(18-23(3)4)48-38(57)32(21-50)49-34(53)27(40)19-24-9-6-5-7-10-24/h5-7,9-10,12-15,22-23,27-32,50-51H,8,11,16-21,40H2,1-4H3,(H2,41,52)(H,45,55)(H,46,54)(H,47,56)(H,48,57)(H,49,53)(H4,42,43,44)/t27-,28-,29-,30-,31-,32-/m0/s1
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| Chemical Name |
(2S)-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanamide
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 100 mg/mL (125.48 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2548 mL | 6.2738 mL | 12.5477 mL | |
| 5 mM | 0.2510 mL | 1.2548 mL | 2.5095 mL | |
| 10 mM | 0.1255 mL | 0.6274 mL | 1.2548 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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