| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Pep2-8 targets proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine protease that promotes the degradation of LDL receptors. PCSK9 binds to the LDL receptor and targets it for lysosomal degradation, thereby reducing LDL cholesterol uptake from the circulation. Pep2-8 binds to PCSK9 with a dissociation constant (KD) of 0.7 µM and inhibits its activity with an IC50 of 1.4 µM. By inhibiting PCSK9, Pep2-8 restores LDL receptor levels and promotes LDL cholesterol uptake.
|
|---|---|
| ln Vitro |
PCSK9 with a shortened C-terminus is bound by Pep2-8[1]. In HepG2 cells treated with PCSK9, Pep2-8 restored LDL uptake to almost 90% of control activity at a dose of 50 μM [1].
In vitro, Pep2-8 demonstrates potent inhibition of PCSK9 activity with an IC50 of 1.4 µM and a binding KD of 0.7 µM. In HepG2 cells treated with PCSK9, Pep2-8 restores LDL uptake to nearly 90% of control activity at a dose of 50 µM. This demonstrates the compound's efficacy in reversing PCSK9-mediated suppression of LDL uptake. Pep2-8 shows concentration-dependent inhibition of PCSK9 binding to LDL receptors and restoration of LDL uptake in cellular models. |
| ln Vivo |
In vivo activity data for Pep2-8 are limited, as the compound is primarily studied in vitro. Based on its PCSK9 inhibitory mechanism, the compound is expected to lower LDL cholesterol levels in animal models of hypercholesterolemia. However, detailed efficacy studies in animal models have not been extensively reported. The compound's peptide nature may limit oral bioavailability, and further development may require formulation optimization for in vivo applications.
|
| Enzyme Assay |
The in vitro binding assay for Pep2-8 typically involves measuring the binding affinity between PCSK9 and the peptide using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Varying concentrations of Pep2-8 are injected over immobilized PCSK9, and binding kinetics are analyzed to determine KD values. For inhibition assays, PCSK9 is pre-incubated with varying concentrations of Pep2-8 (0.01-100 µM) before adding to LDL receptor-coated plates, and bound PCSK9 is detected by ELISA to determine IC50 values.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: HepG2 cell. Tested Concentrations: 15 μg/mL. Incubation Duration: 4 h. Experimental Results: Inhibited PCSK9 activity. For in vitro cell-based assays, HepG2 hepatoma cells or other LDL receptor-expressing cell lines are cultured and treated with PCSK9 and Pep2-8. Cells are incubated with Pep2-8 at concentrations ranging from 1-100 µM for 4-24 hours. LDL uptake is measured using fluorescently labeled LDL or radiolabeled LDL. PCSK9 binding to LDL receptors is assessed by immunoprecipitation or immunofluorescence. LDL receptor levels are measured by Western blot or flow cytometry. |
| Animal Protocol |
In vivo animal studies for Pep2-8 have not been extensively reported. Based on the compound's mechanism as a PCSK9 inhibitor, potential in vivo studies would involve administration to hypercholesterolemic mouse models via intravenous or subcutaneous injection at doses ranging from 1-50 mg/kg. Plasma LDL cholesterol levels would be measured. PCSK9 activity and LDL receptor levels would be assessed in liver tissues. The peptide nature of the compound may require frequent dosing or formulation for sustained release.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Pep2-8 have not been fully characterized. Molecular weight is 1715.85 and molecular formula is C₈₃H₁₁₀N₁₆O₂₄. CAS number is 1541011-97-5. As a peptide, Pep2-8 is expected to have limited oral bioavailability and may require parenteral administration. Detailed pharmacokinetic parameters such as half-life, clearance, and distribution have not been extensively reported. Stability in solution may be limited.
|
| Toxicity/Toxicokinetics |
Toxicology data for Pep2-8 are limited. As a research peptide, it has not been systematically evaluated for safety. The compound's mechanism of PCSK9 inhibition suggests a generally favorable safety profile, but potential immunogenicity and off-target effects of peptide therapeutics require careful assessment. Standard toxicological endpoints should be evaluated. The compound is intended for research use only and is not approved for human use.
|
| References | |
| Additional Infomation |
Pep2-8 is a synthetic peptide PCSK9 inhibitor with a binding KD of 0.7 µM and an IC50 of 1.4 µM. The compound restores LDL uptake in HepG2 cells treated with PCSK9 to nearly 90% of control activity at 50 µM. Pep2-8 is a valuable research tool for studying PCSK9-mediated regulation of cholesterol metabolism and for developing therapeutic strategies for hypercholesterolemia. It is intended for research use only and is not approved for clinical applications.
|
| Molecular Formula |
C83H113N17O24
|
|---|---|
| Molecular Weight |
1732.88484072685
|
| Exact Mass |
1714.787
|
| CAS # |
1541011-97-5
|
| Related CAS # |
Pep2-8 TFA
|
| PubChem CID |
124221781
|
| Appearance |
White to off-white solid powder
|
| LogP |
1.2
|
| Hydrogen Bond Donor Count |
23
|
| Hydrogen Bond Acceptor Count |
24
|
| Rotatable Bond Count |
49
|
| Heavy Atom Count |
123
|
| Complexity |
3630
|
| Defined Atom Stereocenter Count |
15
|
| SMILES |
O=C([C@H](CC(C)C)NC([C@H](CC1C=CC(=CC=1)O)NC([C@H](CCC(=O)O)NC([C@H](CCC(=O)O)NC([C@H](CC1=CNC2C=CC=CC1=2)NC([C@H](CO)NC([C@H]([C@@H](C)O)NC([C@H](CC1C=CC=CC=1)NC([C@H](C(C)C)NC([C@H]([C@@H](C)O)NC(C)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)N[C@@H](CC(=O)O)C(N[C@H](C(N[C@H](C(N)=O)C(C)C)=O)CC1=CNC2C=CC=CC1=2)=O.N
|
| InChi Key |
ORPZALWAWWEEDP-NXXUBLNKSA-N
|
| InChi Code |
InChI=1S/C83H110N16O24/c1-40(2)31-57(74(114)94-62(36-66(109)110)77(117)92-61(79(119)97-67(41(3)4)71(84)111)35-49-38-86-54-22-16-14-20-52(49)54)90-75(115)58(33-47-23-25-50(104)26-24-47)91-73(113)56(28-30-65(107)108)88-72(112)55(27-29-64(105)106)89-76(116)60(34-48-37-85-53-21-15-13-19-51(48)53)93-80(120)63(39-100)96-82(122)70(44(8)102)99-78(118)59(32-46-17-11-10-12-18-46)95-81(121)68(42(5)6)98-83(123)69(43(7)101)87-45(9)103/h10-26,37-38,40-44,55-63,67-70,85-86,100-102,104H,27-36,39H2,1-9H3,(H2,84,111)(H,87,103)(H,88,112)(H,89,116)(H,90,115)(H,91,113)(H,92,117)(H,93,120)(H,94,114)(H,95,121)(H,96,122)(H,97,119)(H,98,123)(H,99,118)(H,105,106)(H,107,108)(H,109,110)/t43-,44-,55+,56+,57+,58+,59+,60+,61+,62+,63+,67+,68+,69+,70+/m1/s1
|
| Chemical Name |
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (58.28 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.46 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5771 mL | 2.8854 mL | 5.7707 mL | |
| 5 mM | 0.1154 mL | 0.5771 mL | 1.1541 mL | |
| 10 mM | 0.0577 mL | 0.2885 mL | 0.5771 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
