| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
| Targets |
The primary target of KGP94 is cathepsin L, a human cysteine protease. KGP94 is a potent, selective inhibitor of cathepsin L with an IC50 of 189 nM. It is a novel, potent, reversible, time-dependent and competitive inhibitor. Cathepsin L is a lysosomal cysteine protease that plays important roles in protein degradation, antigen presentation, and extracellular matrix remodeling. Overexpression of cathepsin L is associated with cancer progression, invasion, and metastasis. By inhibiting cathepsin L, KGP94 can reduce cancer cell migration and invasion.
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| ln Vitro |
KGP94 (10 or 20 μM, 24 hours) decreases cell invasion of primary bone marrow-derived macrophages or Raw264.7 as well as the expression of M2 (macrophage) markers (Arginase-1 and CD206)[3]. Prostate cancer cells' and breast cancer cells' ability to invade is reduced by 53% and 88%, respectively, by KGP94 (25 μM, 24 hours) [4]. In PC-3ML and MDA-MB-231, KGP94 (25 μM, 24 hours) reduced secreted CTSL activity by 94% and 92%, respectively [4]. Assay for cell invasion[4]
KGP94 inhibits the activity of cathepsin L toward human type I collagen. It inhibits migration and invasion of metastatic carcinoma and shows low cytotoxicity (GI50=26.9 µM) against various human cell lines. The compound also inhibits invasion of M2-type macrophages in vitro and reduces macrophage-stimulated invasion of 4T1 mouse breast cancer cells. KGP94 treatment reduces the expression of several M2-related markers, suggesting that cathepsin L activity may be essential for IL-4-driven M0 to M2 differentiation. This indicates that KGP94 may have immunomodulatory effects in addition to its direct anti-tumor activity. |
| ln Vivo |
In a prostate cancer bone metastasis model, KGP94 (ip; 20 mg/kg; once daily for three days) demonstrates anti-metastatic and anti-bone resorbtive effects [5].
No specific in vivo activity data is publicly available for KGP94. The compound is being studied for its potential as a cancer therapeutic, particularly in tumors that rely on the proteasome for survival. It could offer a novel approach to treating various cancers resistant to conventional therapies. The compound's ability to inhibit migration and invasion suggests that it may have anti-metastatic activity in vivo. Its low cytotoxicity (GI50=26.9 µM) against various human cell lines indicates a favorable therapeutic window. |
| Enzyme Assay |
No specific non-cell assay protocol is available for KGP94. For cathepsin L inhibitors, standard cell-free assays use recombinant cathepsin L enzyme and fluorogenic peptide substrates (such as Z-FR-AMC or Z-RR-AMC). The compound is incubated with the enzyme and substrate, and the inhibition of substrate cleavage is measured by fluorescence. These assays provide quantitative data on the compound's potency (IC50) and mechanism of inhibition (competitive, reversible, time-dependent).
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| Cell Assay |
Cell invasion assay[4]
Cell Types: PC-3ML, MDA-MB-231 Tested Concentrations: 10 μM, 25 μM Incubation Duration: 24 hrs (hours) Experimental Results: Attenuated migration and invasion of prostate and breast cancer cells. No specific cell-based assay protocol is available for KGP94. For invasion studies, standard assays use Boyden chamber transwell invasion assays with Matrigel-coated membranes. Cancer cells (e.g., MDA-MB-231) are treated with KGP94 and allowed to invade through the Matrigel. Invaded cells are quantified by staining and microscopy. Cytotoxicity is assessed using MTT or CellTiter-Glo assays to determine GI50 values. For macrophage studies, cells are differentiated to M2 macrophages with IL-4 in the presence or absence of KGP94, and markers of M2 polarization are measured. |
| Animal Protocol |
Animal/Disease Models: NCR nu/nu male mice [5]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 3 days Experimental Results: Metastatic tumor load was diminished by 65%, tumor angiogenesis was diminished by 58%, and increased Survival rate of mice with bone metastasis. No specific animal protocol is available for KGP94. For anti-metastatic studies, standard in vivo models include intravenous injection of cancer cells (e.g., 4T1 breast cancer cells) into mice, followed by compound administration for 2-4 weeks. Metastatic colonies in lungs or other organs are quantified. Alternatively, orthotopic models where cancer cells are implanted into the primary organ site can be used to assess both primary tumor growth and metastatic spread. The compound's effects on macrophage polarization and tumor microenvironment may also be assessed. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KGP94. The compound has a molecular weight of 350.23 and formula C14H12BrN3OS. It has a purity of 99.77%. As a small molecule with moderate lipophilicity, it would be expected to have reasonable oral bioavailability. The compound's selectivity for cathepsin L suggests that it may have favorable distribution properties. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KGP94. The compound shows low cytotoxicity (GI50=26.9 µM) against various human cell lines, suggesting a favorable safety profile. As a cathepsin L inhibitor, potential effects on normal tissues where cathepsin L plays essential roles would need to be assessed. Standard preclinical toxicology would be required for therapeutic development. The compound is for research use only and not for therapeutic applications.
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| References |
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| Additional Infomation |
Structure in the first source
KGP94 has the molecular formula C14H12BrN3OS and molecular weight 350.23. It is a functionalized benzophenone thiosemicarbazone derivative and a selective inhibitor of cathepsin L with an IC50 of 189 nM. The compound inhibits migration and invasion of metastatic carcinoma and shows low cytotoxicity (GI50=26.9 µM) against various human cell lines. It has a purity of 99.77%. No clinical trial status has been identified; it remains a research tool for studying cathepsin L biology and cancer metastasis. |
| Molecular Formula |
C14H12BRN3OS
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|---|---|
| Molecular Weight |
350.233580589294
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| Exact Mass |
348.988
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| CAS # |
1131456-28-4
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| Related CAS # |
1131456-28-4
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| PubChem CID |
52944285
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
377
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1=CC=CC(=C1)/C(/C1C=CC=C(C=1)O)=N\NC(N)=S
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| InChi Key |
ZDBKSZKTCPOBFR-GHRIWEEISA-N
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| InChi Code |
InChI=1S/C14H12BrN3OS/c15-11-5-1-3-9(7-11)13(17-18-14(16)20)10-4-2-6-12(19)8-10/h1-8,19H,(H3,16,18,20)/b17-13+
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| Chemical Name |
[(Z)-[(3-bromophenyl)-(3-hydroxyphenyl)methylidene]amino]thiourea
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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 : ≥ 100 mg/mL (~285.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.14 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 25.0 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: ≥ 2.5 mg/mL (7.14 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 | 2.8553 mL | 14.2763 mL | 28.5527 mL | |
| 5 mM | 0.5711 mL | 2.8553 mL | 5.7105 mL | |
| 10 mM | 0.2855 mL | 1.4276 mL | 2.8553 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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