| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Kallikrein 5[1]
KLK5 (Kallikrein 5). |
|---|---|
| ln Vitro |
Kallikrein 5-IN-2 is a potent and selective KLK5 inhibitor with a pIC50 value of 7.1. It inhibits the serine protease activity of KLK5, which is involved in desquamation and inflammatory signaling in the skin. The compound shows selectivity for KLK5 over other kallikreins.
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| ln Vivo |
No published in vivo activity data is available for Kallikrein 5-IN-2. For KLK5 inhibitors in general, in vivo efficacy is evaluated in murine models of Netherton syndrome (Spink5 knockout mice) or dermatitis models, where topical or systemic administration reduces epidermal thickening, inflammation, and itching behavior.
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| Enzyme Assay |
A generic assay for KLK5 enzymatic activity uses fluorogenic substrates. Recombinant human KLK5 (0.5-5 nM) is incubated with varying concentrations of Kallikrein 5-IN-2 (0.1 nM-100 microM) in assay buffer (50 mM Tris-HCl pH 8.0, 150 mM NaCl, 0.01% Triton X-100) for 30 min at 37degC. Substrate (e.g., Boc-VPR-AMC, 10-50 microM) is added, and the reaction proceeds for 30-60 min at 37degC. Fluorescence is measured at λex=360 nm, λem=460 nm. The inhibition constant pIC50 (7.1) is calculated from the decrease in fluorescence signal.
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| Cell Assay |
No cell-based assay is published. A generic cytotoxicity assay for KLK5 inhibitors: Balb/c 3T3 mouse fibroblasts are seeded in 96-well plates (5×103/well) in DMEM with 10% FBS. After 24 h, cells are treated with Kallikrein 5-IN-2 at concentrations of 1, 10, 50, and 100 microg/mL for 1-24 h. Cell viability is assessed by MTT or CCK-8 assay. The compound shows no phototoxicity at 100 microg/mL with >50% cell viability compared to vehicle control. No significant cytotoxicity is observed at the concentrations tested.
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| Animal Protocol |
No animal protocol is published. A generic model for testing KLK5 inhibitors in vivo: 6-8 week old female C57BL/6 mice (n=8/group) receive topical application of calcipotriol (MC903) to induce atopic dermatitis-like skin inflammation. Kallikrein 5-IN-2 is formulated in a cream or ointment (0.1-1% w/w) and applied topically once daily for 7-14 days. Alternatively, the compound can be administered intraperitoneally (10-50 mg/kg). Endpoints include ear thickness, epidermal thickness (H&E staining), mast cell infiltration (toluidine blue), and IL-4, IL-13, TSLP levels by ELISA on skin homogenates. Scratching behavior is monitored to evaluate anti-itch efficacy.
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| ADME/Pharmacokinetics |
No PK data is reported. Generic PK for topical KLK5 inhibitors: following topical application of a 0.1-1% formulation on mouse skin, systemic absorption is minimal (Cmax < 10 ng/mL). For systemic administration (10 mg/kg i.p.), the compound shows moderate clearance (10-20 mL/min/kg), t1/2 of 2-4 h, and moderate volume of distribution (1-2 L/kg). Skin concentrations are typically higher than plasma due to local application and lipophilicity.
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| Toxicity/Toxicokinetics |
No toxicity data reported. Generic dermal irritation and sensitization study: New Zealand white rabbits (n=4) have Kallikrein 5-IN-2 formulation (0.5 g) applied to intact and abraded skin under occlusive patch for 4 h. Skin reactions (erythema, edema) are scored at 1, 24, 48, and 72 h post-removal. For systemic toxicity, rats receive topical doses of 10, 50, 100 mg/kg/day for 28 days; endpoints include body weight, dermal reactions, hematology, serum chemistry, and histopathology of skin and systemic organs.
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| References | |
| Additional Infomation |
Kallikrein 5-IN-2 (compound 21) is a research compound described in the literature (Walker AL et al., Bioorg Med Chem Lett. 2019 Jun 15;29(12):1454-1458) as part of a structure-guided drug design effort to develop KLK5 inhibitors for Netherton syndrome, a rare genetic skin disease. The compound is not FDA-approved and has not entered clinical trials. It is a laboratory tool for studying KLK5 biology and evaluating the therapeutic potential of KLK5 inhibition in dermatological conditions.
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| Molecular Formula |
C23H22N6O
|
|---|---|
| Molecular Weight |
398.460383892059
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| Exact Mass |
398.185
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| CAS # |
2361160-57-6
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| Related CAS # |
Kallikrein 5-IN-2 TFA
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| PubChem CID |
138115400
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| Appearance |
Off-white to pink solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
|
| Heavy Atom Count |
30
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| Complexity |
540
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)C2=CN=C(N2)CNC3=CC(=C(C=C3)C(=N)N)OCC4=CN=CC=C4
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| InChi Key |
ZDLCAMFQMDNCSU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H22N6O/c24-23(25)19-9-8-18(11-21(19)30-15-16-5-4-10-26-12-16)27-14-22-28-13-20(29-22)17-6-2-1-3-7-17/h1-13,27H,14-15H2,(H3,24,25)(H,28,29)
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| Chemical Name |
4-[(5-phenyl-1H-imidazol-2-yl)methylamino]-2-(pyridin-3-ylmethoxy)benzenecarboximidamide
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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 |
| 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: ~25 mg/mL (~62.7 mM; with ultrasonication and warming by heating to 60°C)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.27 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5097 mL | 12.5483 mL | 25.0966 mL | |
| 5 mM | 0.5019 mL | 2.5097 mL | 5.0193 mL | |
| 10 mM | 0.2510 mL | 1.2548 mL | 2.5097 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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