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Purity: ≥98%
| Targets |
GSTO1-IN-1 targets glutathione S-transferase omega 1 (GSTO1), an atypical GST isoform that is overexpressed in several cancers and has been implicated in drug resistance. GSTO1 is a member of the omega class of glutathione transferases and plays a role in cellular detoxification, redox regulation, and stress responses. Unlike other GSTs, GSTO1 has a cysteine residue in its active site that can form covalent adducts with electrophilic compounds. GSTO1-IN-1 contains a chloroacetamide moiety that covalently binds to this active site cysteine, resulting in irreversible inhibition of the enzyme. The compound has an IC50 of 31 nM for GSTO1. Co-crystal structures demonstrate covalent binding to the active site cysteine.
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| ln Vitro |
GSTO1-IN-1 (C1-27) has an IC50 value of 31 nM, which is an effective inhibitor of GSTO1 enzyme activity. When it comes to binding to recombinant proteins and endogenous GSTO1 in a soluble proteomic context, GSTO1-IN-1 also faces competition from 5-chloromethylfluorescein diacetate (CMFDA). A dose-dependent reduction in cell viability was also seen in HCT116 cells treated with GSTO1-IN-1. At submicromolar concentrations, GSTO1-IN-1 prevents HCT116 cell clonal survival [1].
GSTO1-IN-1 is a potent inhibitor of GSTO1 enzyme activity with an IC50 of 31 nM. The compound competes with 5-chloromethylfluorescein diacetate (CMFDA) for binding to recombinant proteins and endogenous GSTO1 in a soluble proteomic context. In HCT116 colorectal cancer cells, GSTO1-IN-1 causes a dose-dependent reduction in cell viability and prevents clonal survival at submicromolar concentrations. The compound suppresses cancer cell growth and enhances the cytotoxic effects of cisplatin. Bru-seq-based transcription profiling has revealed novel roles for GSTO1 in cholesterol metabolism, oxidative and endoplasmic stress responses, cytoskeleton organization, and cell migration. |
| ln Vivo |
GSTO1-IN-1's effects were assessed in a human colon cancer cell line xenograft model in order to determine whether it is effective in vivo. HCT116 xenograft-bearing nude mice received a single dose of GSTO1-IN-1 (20–45 mg/kg). Following a 5-week course of treatment, the tumor growth of mice in the GSTO1-IN-1 treatment group was considerably suppressed (P<0.05) in comparison to the vehicle treatment group. Throughout the course of the trial, mice showed no overt toxicity and generally tolerated treatment with GSTO1-IN-1 up to 45 mg/kg with no discernible side effects or changes in average body weight [1].
GSTO1-IN-1 has demonstrated in vivo efficacy in a human colon cancer cell line xenograft model. HCT116 xenograft-bearing nude mice received a single dose of GSTO1-IN-1 (20-45 mg/kg). Following a 5-week course of treatment, tumor growth in the GSTO1-IN-1 treatment group was considerably suppressed (P<0.05) compared to the vehicle treatment group. Throughout the course of the trial, mice showed no overt toxicity and generally tolerated treatment with GSTO1-IN-1 up to 45 mg/kg with no discernible side effects or changes in average body weight. These findings demonstrate the therapeutic utility of GSTO1 inhibitors as anticancer agents. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for GSTO1-IN-1 measures the inhibition of GSTO1 enzymatic activity. Recombinant human GSTO1 is incubated with varying concentrations of GSTO1-IN-1 (typically ranging from nanomolar to micromolar) in the presence of glutathione and a substrate such as CDNB or a fluorogenic substrate. The enzymatic reaction is monitored spectrophotometrically or fluorometrically. The IC50 value of 31 nM is determined by fitting dose-response curves to the inhibition data. The compound's covalent binding to the active site cysteine can be confirmed by mass spectrometry or co-crystallization studies. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations, with DMSO concentration kept constant across all wells. Appropriate positive controls and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for GSTO1-IN-1 is performed using HCT116 colorectal cancer cells. Cells are cultured in appropriate medium and treated with varying concentrations of GSTO1-IN-1 (typically submicromolar to micromolar) or vehicle control (DMSO) for specified time points (e.g., 48-72 hours). Cell viability is assessed using assays such as MTT, CellTiter-Glo, or colony formation assays. The compound's ability to inhibit clonal survival is evaluated by plating cells at low density and allowing colonies to form over 7-14 days in the presence of the compound. Additionally, the effects of GSTO1-IN-1 on GSTO1 activity can be assessed by measuring the competition with CMFDA binding to endogenous GSTO1 in cell lysates.
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| Animal Protocol |
In vivo animal experiments with GSTO1-IN-1 were conducted using a human colon cancer cell line xenograft model in nude mice. HCT116 cells were implanted subcutaneously into the flank of nude mice. When tumors reached a predetermined size, animals were randomized into treatment groups receiving GSTO1-IN-1 at doses of 20-45 mg/kg or vehicle control. The compound was administered via intraperitoneal (IP) injection, likely on a daily or scheduled basis. Tumor volume was measured twice weekly using calipers, and body weight was monitored to assess tolerability. At the end of the 5-week treatment period, tumors were harvested for analysis of GSTO1 activity, proliferation markers, and apoptosis. The study demonstrated significant tumor growth suppression with no overt toxicity.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for GSTO1-IN-1 are not extensively documented in publicly available sources. As a small-molecule inhibitor with a molecular weight of 311.18 and a chloroacetamide moiety, the compound may have moderate oral bioavailability. GSTO1-IN-1 is soluble in DMSO at ≥300 mg/mL. For in vivo administration, the compound was formulated for intraperitoneal injection at doses of 20-45 mg/kg. The compound should be stored as a powder at -20°C (stable for up to 3 years) or at 4°C (stable for up to 2 years), and in solution at -80°C (stable for up to 6 months) or -20°C (stable for up to 1 month). Detailed PK parameters including half-life, clearance, and bioavailability are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
GSTO1-IN-1 was well-tolerated in animal studies at doses up to 45 mg/kg, with no discernible side effects or changes in average body weight observed throughout the 5-week treatment period. As a research-grade compound, GSTO1-IN-1 is intended for laboratory research purposes only and is not approved for human use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound contains a chloroacetamide moiety, which is a reactive electrophile that can form covalent adducts with nucleophilic residues in proteins. Care should be taken to avoid exposure and to handle the compound in accordance with institutional safety guidelines. Comprehensive toxicological profiling beyond the in vivo study is not available from the current search results.
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| References | |
| Additional Infomation |
GSTO1-IN-1 is a research compound developed for studying the role of GSTO1 in cancer, drug resistance, and cellular stress responses. The compound is a potent and selective inhibitor of GSTO1 with an IC50 of 31 nM. It covalently binds to the active site cysteine of GSTO1 and has demonstrated efficacy in suppressing cancer cell growth and tumor growth in colon cancer models. Transcriptional profiling has revealed novel roles for GSTO1 in cholesterol metabolism, oxidative and endoplasmic stress responses, cytoskeleton organization, and cell migration. GSTO1-IN-1 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical cancer research. The compound is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C10H12N2O3SCL2
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|---|---|
| Molecular Weight |
311.18488
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| Exact Mass |
309.994
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| CAS # |
568544-03-6
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| PubChem CID |
3860347
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.591
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| LogP |
1.25
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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 |
4
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| Heavy Atom Count |
18
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| Complexity |
394
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)S(=O)(=O)C1=C(C=CC(=C1)NC(=O)CCl)Cl
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| InChi Key |
YEHYODCKTNLFQU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H12Cl2N2O3S/c1-14(2)18(16,17)9-5-7(3-4-8(9)12)13-10(15)6-11/h3-5H,6H2,1-2H3,(H,13,15)
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| Chemical Name |
2-chloro-N-[4-chloro-3-(dimethylsulfamoyl)phenyl]acetamide
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| Synonyms |
GSTO1-IN-2; GSTO1 IN2; GSTO1 IN-2
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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 : ≥ 300 mg/mL (~964.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.03 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 (8.03 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 25.0 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: ≥ 2.5 mg/mL (8.03 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 | 3.2136 mL | 16.0679 mL | 32.1357 mL | |
| 5 mM | 0.6427 mL | 3.2136 mL | 6.4271 mL | |
| 10 mM | 0.3214 mL | 1.6068 mL | 3.2136 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.
 Identification and characterization of C1-27 as a potent GSTO1 inhibitor.Nat Commun.2016 Oct 5;7:13084. |
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 GSTO1 inhibition impedes cancer cell viability.Nat Commun.2016 Oct 5;7:13084. |
 C1-27 inhibits colorectal cancer tumour growthin vivo.Nat Commun.2016 Oct 5;7:13084. |
 C1-27 is a covalent GSTO1 inhibitor.Nat Commun.2016 Oct 5;7:13084. |
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 Analysis of gene expression following C1-27 treatment and GSTO1 knockdown.Nat Commun.2016 Oct 5;7:13084. |
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