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| Targets |
S130 selectively targets ATG4B (autophagy-related 4B cysteine protease) with high affinity. ATG4B is a cysteine protease that processes the LC3 precursor protein by cleaving its C-terminal peptide, exposing a glycine residue that is essential for LC3 conjugation to phosphatidylethanolamine (PE) during autophagosome formation. ATG4B also deconjugates LC3 from the autophagosome membrane, allowing recycling of LC3. By inhibiting ATG4B, S130 disrupts both the initiation and the recycling phases of autophagy, leading to the accumulation of lipidated LC3 in autolysosomes and the suppression of autophagic flux. The compound exhibits an IC₅0 of 3.24 microM for ATG4B.
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| ln Vitro |
S130 causes increased cytotoxicity by blocking ATG4B, which in turn stops autophagy and triggers apoptosis [1]. S130 (10 μM; 6 hours) suppresses autophagy in late autolysosomal degradation or early LC3 initiation [1]. More lipidated LC3 is accumulated in autolysosomes by S130 [1]. At doses greater than 6.3 μM, ATG4B activity is inhibited by S130 (0-25 μM; 48 hours), which results in cell death. Also, necroptosis—the process by which cells die—may not result from this cytotoxicity [1]. S130-induced cytotoxicity is increased by malnutrition [1]. S130 (0-10 μM; 24 hours) prevented ATG4B KO cells from cleaving full-length LC3-GST by roughly 79% at 10 μM without consuming any substrate. The effect of S130 on ATG4B is strongly inhibitory [1].
In vitro, S130 inhibits ATG4B with an IC₅0 of 3.24 microM. S130 (10 microM; 6 hours) suppresses autophagy in late autolysosomal degradation or early LC3 initiation. The compound leads to the accumulation of lipidated LC3 in autolysosomes. By blocking ATG4B, S130 inhibits autophagy flux, resulting in the accumulation of autophagosomes and impaired degradation of autophagic cargo. The inhibition of autophagy by S130 activates apoptosis, leading to enhanced cytotoxicity in cancer cells. The compound has shown significant potential in scientific research, particularly in the fields of autophagy, cancer biology, and drug discovery. S130 is used to study the functional role of ATG4B in various cellular processes. |
| ln Vivo |
In vivo, S130 (20 mg/kg; intraperitoneal injection; daily; 3-week duration) effectively suppresses tumor development and exhibits anti-tumor effects while maintaining a favorable safety profile for critical organs [1].
In vivo data for S130 are limited as the compound is primarily used in in vitro studies. The compound's ability to suppress autophagy and induce apoptosis suggests potential antitumor activity in vivo. However, specific animal studies have not been extensively reported. The compound is intended for research use only and has not been evaluated in clinical trials. The pharmacokinetic properties, bioavailability, and tissue distribution of S130 have not been characterized. Researchers interested in in vivo applications should consult the primary literature for the most current information. |
| Enzyme Assay |
In vitro enzyme assays for S130 involve measuring ATG4B protease activity using recombinant human ATG4B enzyme and a fluorogenic peptide substrate. The assay is performed in reaction buffer containing DTT or other reducing agents to maintain the cysteine protease activity. S130 is added at varying concentrations (0.001-100 microM) and pre-incubated with the enzyme for 10-30 minutes. The fluorogenic substrate (e.g., a peptide derived from the LC3 C-terminus with a fluorophore-quencher pair) is then added, and fluorescence increase is monitored over time at 37degC using a fluorescence plate reader. Initial reaction rates are calculated, and IC₅0 values are determined from dose-response curves using nonlinear regression. Selectivity is assessed by testing S130 against other cysteine proteases and related enzymes.
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| Cell Assay |
Cytotoxicity assay [1]
Cell Types: HeLa cells, HCT116 cells, HL60 cells Tested Concentrations: 0 μM, 3.1 μM, 6.3 μM, 12.5 μM, 25 μM Incubation Duration: 48 hrs (hours) Experimental Results: Significant cytotoxic effect on HeLa cells (IC50 = 16.1 µM), HCT116 cells (IC50 = 9.0 µM) and HL60 cells (IC50 = 4.7 µM) at doses above 6.3 µM. And this cytotoxicity may not lead to cell death via necroptosis. Autophagy assay [1] Cell Types: HeLa cells and MEF cells Tested Concentrations: 10 μM Incubation Duration: 6 hrs (hours) Experimental Results: Inhibition of autophagy in the early stage of LC3 initiation or late stage of autolysosomal degradation. Western Blot Analysis[1] Cell Types: HeLa Cell Tested Concentrations: 0 μM, 5 μM, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: 10 μM inhibited ~79% cleavage of full-length LC3-GST with no substrate in ATG4B KO processed in cells. Cellular assays for S130 are performed using cancer cell lines to assess autophagy inhibition and apoptosis induction. Cells (e.g., HeLa, MCF-7, or HCT116) are cultured in appropriate medium and seeded in 6- or 96-well plates. Cells are treated with S130 at concentrations ranging from 0.1-25 microM for 6-24 hours. Autophagy flux is assessed by Western blotting for LC3-II accumulation and p62/SQSTM1 levels. Lysosomal inhibition (using chloroquine or bafilomycin A1) is used to distinguish between autophagosome accumulation and impaired autophagosome-lysosome fusion. Apoptosis is evaluated by caspase-3/7 activity, Annexin V/PI staining, and PARP cleavage. Cell viability is measured using MTT or CellTiter-Glo assays. The relationship between ATG4B inhibition, autophagy suppression, and apoptosis induction is characterized. |
| Animal Protocol |
Animal/Disease Models: BALB/c female nude mice (4 weeks), HCT116 cell xenotransplantation [1]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; 3 weeks Experimental Results: able to inhibit tumor growth and have effects on important organs Good security. In vivo animal studies for S130 have not been extensively reported in the literature. The compound is primarily a research tool for in vitro studies of autophagy. For in vivo applications, researchers may consider using S130 in xenograft mouse models to evaluate antitumor efficacy. In such studies, S130 could be administered intraperitoneally or orally at doses determined by pharmacokinetic studies. Tumor volume, body weight, and survival would be monitored. Autophagy and apoptosis markers would be assessed in tumor tissues by immunohistochemistry and Western blotting. However, specific protocols and dosing regimens have not been established. Researchers should consult the primary literature for the most current information. |
| ADME/Pharmacokinetics |
S130 (CAS#: 1160852-22-1) has molecular formula C24H2₅N3O2 and molecular weight 387.47. The compound's chemical name is N-[3-(diethylamino)propyl]-7-oxo-7H-dibenzo[de,g]quinoline-4-carboxamide. It is a high-affinity, selective inhibitor of the cysteine protease ATG4B with an IC₅0 of 3.24 microM. S130 suppresses autophagy flux and activates apoptosis, leading to enhanced cytotoxicity. The compound is a solid and should be stored at -20degC. It is soluble in DMSO and is intended for research use only, not for human therapeutic applications.
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| Toxicity/Toxicokinetics |
Toxicological information for S130 is limited as the compound is a research chemical. Based on its mechanism of ATG4B inhibition and autophagy suppression, potential toxicities may include effects on tissues with high autophagic activity, such as the liver, kidney, and immune cells. The compound should be handled with standard laboratory precautions including the use of personal protective equipment (gloves, lab coat, safety goggles) and working in a well-ventilated fume hood. Avoid inhalation, ingestion, and skin contact. The compound should be stored desiccated at -20degC and disposed of according to institutional guidelines for hazardous waste.
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| References | |
| Additional Infomation |
S130 (CAS#: 1160852-22-1) is a high-affinity, selective inhibitor of ATG4B, a key cysteine protease in the autophagy pathway. ATG4B is responsible for the proteolytic processing of LC3, a critical step in autophagosome formation and maturation. By inhibiting ATG4B, S130 suppresses autophagy flux and triggers apoptosis, leading to enhanced cytotoxicity. This compound is used in research to study the role of autophagy in cancer cell survival, drug resistance, and as a potential therapeutic strategy for autophagy-dependent cancers. The compound has an IC₅0 of 3.24 microM for ATG4B. S130 is supplied for research use only and is not approved for any clinical indication. As of the current date, S130 remains a preclinical research compound.
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| Molecular Formula |
C24H25N3O2
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| Molecular Weight |
387.474205732346
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| Exact Mass |
387.194
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| CAS # |
1160852-22-1
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| PubChem CID |
44128205
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| Appearance |
White to off-white solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
591
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2C=CC=CC=2C2C=CC=C3C(=CN=C1C=23)C(NCCCN(CC)CC)=O
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| InChi Key |
DZUCZYXRADUTMW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25N3O2/c1-3-27(4-2)14-8-13-25-24(29)20-15-26-22-21-17(11-7-12-18(20)21)16-9-5-6-10-19(16)23(22)28/h5-7,9-12,15H,3-4,8,13-14H2,1-2H3,(H,25,29)
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| Chemical Name |
N-[3-(diethylamino)propyl]-8-oxo-10-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2,4,6,9,11,13(17),14-octaene-12-carboxamide
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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 : ~125 mg/mL (~322.61 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.81 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 22.5 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: ≥ 2.25 mg/mL (5.81 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 22.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5808 mL | 12.9042 mL | 25.8084 mL | |
| 5 mM | 0.5162 mL | 2.5808 mL | 5.1617 mL | |
| 10 mM | 0.2581 mL | 1.2904 mL | 2.5808 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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