| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Glutathione S-Transferase Pi (GSTP1). LAS17 is a tyrosine-directed irreversible inhibitor targeting GSTP1. It binds covalently to the active site of this isozyme, blocking its role in detoxification and cellular defense against reactive electrophiles, and disrupting oncogenic signaling pathways such as AMPK/ACC.
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| ln Vitro |
Cellular defense against reactive electrophiles is mediated by glutathione S-Transferase Pi (GSTP1). GSTP1 activity is in vitro inhibited by LAS17 in a concentration-dependent manner[1]. Treatment with LAS17 (10 µM; serum-free survival 48 h) in 231MFP breast cancer cells reproduces the impairments in serum-free cell survival linked to genetic GSTP1 inactivation[2]. When 231MFP cells are treated with LAS17 (10 µM) and GSTP1 knockdown, the levels of phosphorylated AMPK and acetyl CoA carboxylase (ACC) rise[2]. A decrease in ATP, lactic acid, purine nucleotides, diacylated phospholipids, and alkylacyl ether lipids is also observed in 231MFP cells, while an increase is seen in acyl carnitines (ACs), ceramides, and lysophospholipids[2].
LAS17 inhibits GSTP1 activity with an IC50 of 0.5 uM in a concentration-dependent manner. In 231MFP breast cancer cells, treatment with LAS17 (10 uM) recapitulates the metabolic and signaling impairments observed with genetic knockout of GSTP1. This includes increased levels of phosphorylated AMPK and ACC, reduced ATP and lactic acid, and alterations in lipid metabolism. |
| ln Vivo |
When treatment is started two days after subcutaneous cell injection, LAS17 (20 mg/kg ip, once daily) significantly inhibits the growth of 231MFP breast tumor xenografts in immune-deficient mice. When treatment is started sixteen days after tumor implantation, LAS17 even slows tumor growth without causing any noticeable toxicity or weight change[2].
In a 231MFP triple-negative breast cancer (TNBC) xenograft model, daily intraperitoneal administration of LAS17 (20 mg/kg) significantly impaired tumor growth, even when treatment was initiated 16 days after tumor implantation. These in vivo results were achieved with no observable toxicity and no significant change in mouse body weight, suggesting a favorable therapeutic window for this investigational compound. |
| Enzyme Assay |
Standard GSTP1 enzyme assays are performed in 96-well plates. Purified recombinant human GSTP1 is incubated with the model substrate 1-chloro-2,4-dinitrobenzene (CDNB) and reduced glutathione (GSH). LAS17 is added at increasing concentrations (0.1-10 uM). The conjugation reaction is monitored by the increase in absorbance at 340 nm due to the formation of the thioether product. IC50 values are calculated from the kinetic curves.
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: 231MFP breast cancer cells Tested Concentrations: 10 µM Incubation Duration: 48 hrs (hours) Experimental Results: Recapitulated the serum-free cell survival impairments observed with genetic inactivation of GSTP1. Western Blot Analysis[2] Cell Types: 231MFP cells Tested Concentrations: 10 µM Incubation Duration: Experimental Results: LAS17- Treated 231MFP cells show increased levels of phosphorylated AMPK and ACC. For mechanistic cell culture studies, 231MFP triple-negative breast cancer cells are treated with LAS17 (0-20 uM) for 24-48 hours. Cells are harvested, and protein lysates are analyzed by Western blot. Specific readouts include the phosphorylation status of AMPK and ACC. Metabolomic profiling is performed on cell extracts to measure levels of ATP, lactate, and lipid species via LC-MS/MS. |
| Animal Protocol |
Animal/Disease Models: Severe combined immunodeficiency (SCID) mice bearing 231MFP tumor xenograft[2]
Doses: 20 mg/kg (prepared in PBS:ethanol: PEG40 (18: 1:1)) Route of Administration: Daily administration ip, once per day Experimental Results: Dramatically impaired 231MFP breast tumor xenograft growth. In vivo studies are conducted using a subcutaneous 231MFP xenograft model in immunodeficient mice. LAS17 is formulated in a suitable vehicle (e.g., PBS with a co-solvent) and administered intraperitoneally (IP) at 20 mg/kg once daily, starting either at early (Day 2) or late (Day 16) stages of tumor development. Tumor dimensions are measured with calipers, and body weight is monitored for toxicity. Tumors are harvested for Western blot analysis and histology at endpoint. |
| ADME/Pharmacokinetics |
LAS17 is a small molecule with a molecular weight of 359.25 g/mol and a molecular formula of C15H20Cl2N4O2. It is soluble in DMSO. The compound is stable as a powder and should be stored at -20degC for long-term stability. For in vivo studies, LAS17 can be formulated using vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline to ensure appropriate bioavailability.
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| Toxicity/Toxicokinetics |
Published in vivo studies indicate that LAS17 has a favorable toxicity profile at the efficacious dose of 20 mg/kg, with no observable toxicity and no significant weight change in mice. However, comprehensive standard toxicology studies (e.g., 28-day repeat-dose toxicity in rats) have not been published. As a covalent inhibitor, caution should be exercised due to potential off-target reactivity, but the tyrosine-directed mechanism suggests selectivity.
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| References | |
| Additional Infomation |
LAS17 is a chemical probe used to study the role of GSTP1 in cancer metabolism, particularly in triple-negative breast cancer. It is not an FDA-approved drug. Its utility lies in its ability to irreversibly inhibit GSTP1, a protein that drives cancer cell pathogenicity and metabolism, making it a valuable tool for target validation studies.
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| Molecular Formula |
C15H20CL2N4O2
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| Molecular Weight |
359.250901222229
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| Exact Mass |
358.096
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| CAS # |
2362527-67-9
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| PubChem CID |
156024492
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| Appearance |
Colorless to light yellow ointment
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
23
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| Complexity |
417
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)C[C@H](C(=O)OC)N(CCCC#C)C1=NC(=NC(=N1)Cl)Cl
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| InChi Key |
UTXOIMJGBZBFGA-LLVKDONJSA-N
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| InChi Code |
InChI=1S/C15H20Cl2N4O2/c1-5-6-7-8-21(11(9-10(2)3)12(22)23-4)15-19-13(16)18-14(17)20-15/h1,10-11H,6-9H2,2-4H3/t11-/m1/s1
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| Chemical Name |
methyl (2R)-2-[(4,6-dichloro-1,3,5-triazin-2-yl)-pent-4-ynylamino]-4-methylpentanoate
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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 (278.36 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7836 mL | 13.9179 mL | 27.8358 mL | |
| 5 mM | 0.5567 mL | 2.7836 mL | 5.5672 mL | |
| 10 mM | 0.2784 mL | 1.3918 mL | 2.7836 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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