| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cathepsin C
Cathepsin C (Cat C) |
|---|---|
| ln Vitro |
With IC50s of 115.4 and 70.2 nM, respectively, cathepsin C-IN-5 (compound SF38) shows inhibitory effects in THP-1 and U937 cells [1].
Cathepsin C-IN-5 exhibits high potency and selectivity for Cathepsin C, with an IC50 of 59.9 nM. It shows significantly lower activity against other cathepsins (Cat L: 4.26 uM, Cat S, Cat B, Cat K: all >5 uM). It effectively inhibits Cat C activity in bone marrow and blood, leading to reduced NSP activation. |
| ln Vivo |
In ICR mice, cathepsin C-IN-5 (1500 mg/kg) did not cause any appreciable weight loss or toxicity during 7 days of dosing[1]. The bioavailability of cathepsin C-IN-5 (oral 10 mg/kg; intravenous 2 mg/kg) is good (F=42.07%)[1]. In animal models of acute lung injury (ALI), cathepsin C-IN-5 (2, 10, 50 mg/kg; po) exhibits strong anti-inflammatory action and possible protective benefits[1].
In vivo, Cathepsin C-IN-5 demonstrates good oral bioavailability (F=42.07%). At doses of 2, 10, and 50 mg/kg (p.o.), it shows effective anti-inflammatory activity and potential protective effects in an animal model of acute lung injury (ALI). No significant weight loss or toxic reaction is observed at 1500 mg/kg within 7 days. |
| Enzyme Assay |
Cathepsin C activity is measured using a fluorogenic substrate such as H-Gly-Phe-AMC or H-Gly-Arg-AMC. The compound is pre-incubated with the enzyme in an assay buffer (e.g., 50 mM MES, pH 6.5, 50 mM NaCl, 5 mM DTT) for 10 minutes at room temperature. The reaction is initiated by adding the substrate, and fluorescence is monitored (Ex/Em=380/460 nm).
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| Cell Assay |
Cathepsin C-IN-5 shows inhibition in THP-1 and U937 human monocytic cell lines with IC50s of 115.4 nM and 70.2 nM, respectively. Cells are treated with the compound for 1 hour, then lysed. Cathepsin C activity is measured in the lysates. The effect on downstream NSP activity is measured using selective substrates.
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| Animal Protocol |
Animal/Disease Models: C57BL/6 male mice (acute lung injury (ALI) mice model)[1]
Doses: 2, 10, 50 mg/kg (one hour after administration, received LPS (20 mg/kg)) Route of Administration: Po Experimental Results: diminished the levels of proinflammatory cytokines (TNF-a, IL-6, and GM-CSF) and increased the concentration of the anti-inflammatory cytokine (IL-10) in a dose-dependent manner. For PK and efficacy studies, ICR mice are used. For PK: 10 mg/kg (p.o.) and 2 mg/kg (i.v.) are administered to determine oral bioavailability (F=42.07%). For efficacy: A mouse model of ALI is established by intratracheal LPS instillation. Cathepsin C-IN-5 (2, 10, 50 mg/kg) is given orally 1 hour before and 6 hours after LPS. Bronchoalveolar lavage fluid and lung tissue are collected for analysis. |
| ADME/Pharmacokinetics |
Cathepsin C-IN-5 has a molecular weight of 436.92. Its pharmacokinetic parameters are: oral bioavailability (F) of 42.07% in mice. It is orally active and shows a favorable PK profile. The compound is administered orally and exhibits a moderate half-life. More detailed PK parameters (t1/2, Cmax) are available in the primary literature.
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| Toxicity/Toxicokinetics |
Cathepsin C-IN-5 shows no significant weight loss or toxic reaction within 7 days after administration in ICR mice at a high dose of 1500 mg/kg. This suggests a wide safety margin. No other specific toxicities or adverse effects have been reported for this research compound.
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| References | |
| Additional Infomation |
Cathepsin C-IN-5 is a research compound that functions as a non-peptidyl, non-covalent Cathepsin C inhibitor. It is a valuable tool for studying the role of Cathepsin C and neutrophil serine proteases (NSPs) in various inflammatory diseases, such as acute lung injury (ALI), bronchiectasis, and COPD. It has not progressed to clinical trials.
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| Molecular Formula |
C21H17CLN6OS
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|---|---|
| Molecular Weight |
436.917280912399
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| Exact Mass |
436.087
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| CAS # |
2825567-97-1
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| PubChem CID |
163409160
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| Appearance |
White to off-white solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
572
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC1=CC=CC(NC2C(Cl)=CN=C(NC3=NC=C(C4C=CSC=4)C=C3)N=2)=C1)(=O)C
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| InChi Key |
CVEIEBFUSJRUSP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H17ClN6OS/c1-13(29)25-16-3-2-4-17(9-16)26-20-18(22)11-24-21(28-20)27-19-6-5-14(10-23-19)15-7-8-30-12-15/h2-12H,1H3,(H,25,29)(H2,23,24,26,27,28)
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| Chemical Name |
N-[3-[[5-chloro-2-[(5-thiophen-3-ylpyridin-2-yl)amino]pyrimidin-4-yl]amino]phenyl]acetamide
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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: 20 mg/mL (45.77 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (4.58 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 20.0 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 | 2.2887 mL | 11.4437 mL | 22.8875 mL | |
| 5 mM | 0.4577 mL | 2.2887 mL | 4.5775 mL | |
| 10 mM | 0.2289 mL | 1.1444 mL | 2.2887 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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