| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
(R)-GSK 2830371 targets the Wip1 phosphatase (wild-type p53-induced phosphatase 1, also known as PPM1D). Wip1 is a serine/threonine phosphatase that dephosphorylates and inactivates key DNA damage response (DDR) proteins, including p53 (at Ser15), Chk2 (at Thr68), ATM (at Ser1981), and H2AX (at Ser139). As an allosteric inhibitor, (R)-GSK 2830371 binds to the catalytic domain of Wip1, blocking its activity. This leads to sustained activation of p53 and Chk2, resulting in cell cycle arrest and apoptosis in cancer cells. The compound is highly selective for Wip1 over 21 other phosphatases.
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| ln Vitro |
In vitro, GSK 2830371 potently inhibits Wip1-mediated dephosphorylation of the FDP substrate and endogenous substrates p38 MAPK (T180) with IC50 values of 6 nM and 13 nM, respectively. In PPM1D-amplified MCF-7 breast carcinoma cells, GSK2830371 increases phosphorylation of multiple Wip1 substrates (p53, Chk2, ATM, H2AX). The compound induces Chk2/p53-mediated apoptosis in neuroblastoma cells in a p53-dependent manner. It also inhibits the growth of a wide range of cancer cells in vitro. In vitro, (R)-GSK 2830371 is the less active R-enantiomer.
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| ln Vivo |
In vivo, GSK2830371 (the racemate or S-enantiomer) is orally active. In DOHH2 tumor-bearing mice, oral administration (150 mg/kg) increases phosphorylation of Chk2 (T68) and p53 (S15) and decreases Wip1 protein concentrations in tumors. GSK2830371 (150 mg/kg p.o.) also significantly inhibits the growth of DOHH2 tumor xenografts. The combination of GSK2830371 with MDM2 inhibitors has been shown to be efficacious in the treatment of various cancers, including liver adenocarcinoma, acute myeloid leukemia, and breast cancer.
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| Enzyme Assay |
In vitro Wip1 phosphatase inhibition assay: The activity of purified recombinant human Wip1 (PPM1D) is measured using a phosphopeptide substrate (e.g., FITC-labeled p53-derived peptide). Wip1 (0.5-5 nM) is incubated in assay buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 5 mM DTT, 0.01% Tween-20) with 10 uM substrate and varying concentrations of (R)-GSK 2830371 (0.1-1000 nM) at 30degC for 30-60 min. The reaction is terminated by adding a stop solution, and the fluorescence polarization is measured. IC₅0 (6 nM for the S-enantiomer) is calculated from the dose-response curve. For selectivity, the compound is tested against a panel of 21 phosphatases.
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| Cell Assay |
For cell-based assays, PPM1D-amplified cancer cells (e.g., MCF-7, DOHH2) are seeded in 6-well plates (3×10⁵ cells/well) and treated with (R)-GSK 2830371 (1-1000 nM) for 6-24 h. Cell lysates are prepared, and phosphorylation of p53 (Ser15), Chk2 (Thr68), ATM (Ser1981), and H2AX (Ser139) is assessed by Western blotting using phospho-specific antibodies. Total protein levels are used as loading controls. Cell viability is measured by MTT assay after 48-72 h. Apoptosis is confirmed by Annexin V/PI staining and flow cytometry.
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| Animal Protocol |
In vivo xenograft model: Female BALB/c nude mice (6-8 wk, n=8-10/group) are subcutaneously inoculated with 5×10⁶ PPM1D-amplified cancer cells (e.g., DOHH2). When tumors reach ~100-150 mm3, mice are randomized. GSK2830371 is formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline and administered orally (PO) at doses of 50-200 mg/kg once daily for 2-3 weeks. Tumor volume is measured every 3 days with calipers. At endpoint, tumors are excised for Western blotting (p-p53, p-Chk2, p-H2AX) and immunohistochemistry (Ki-67, cleaved caspase-3). Body weight is monitored for toxicity. (R)-GSK 2830371 is the less active enantiomer and may not show efficacy in vivo.
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| ADME/Pharmacokinetics |
GSK2830371 is an orally active small molecule (MW of free base: 394.42). Following oral administration (150 mg/kg in mice), peak plasma concentrations (Cmax) are achieved within 1-2 hours. The half-life (t½) in rodents is approximately 2-4 hours. The compound has moderate to good oral bioavailability (estimated 30-60%). It is metabolized in the liver by CYP450 enzymes. Excretion is in urine and feces. (R)-GSK 2830371 is the less active enantiomer and is used as a control.
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| Toxicity/Toxicokinetics |
For GSK2830371, in vivo studies in mice at doses up to 150 mg/kg (PO) did not show significant body weight loss or overt toxicity. Common adverse effects may include thrombocytopenia and neutropenia due to p53 activation. For (R)-GSK 2830371, standard safety precautions for handling research chemicals apply: use PPE (gloves, lab coat, safety goggles), work in a fume hood, avoid inhalation and skin contact. Not for human consumption.
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| References | |
| Additional Infomation |
(R)-GSK 2830371 (CAS# 2743427-27-0) is a research-grade negative control (the less active R-enantiomer) for the Wip1 inhibitor GSK2830371. It is not an FDA-approved drug. For research use only, not for diagnostic or therapeutic applications. Storage: powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month. Purity: ≥98%.
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| Molecular Formula |
C23H29CLN4O2S
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| Molecular Weight |
461.02
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| CAS # |
2743427-27-0
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| Related CAS # |
GSK 2830371;1404456-53-6
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| Appearance |
Off-white to light yellow solid powder
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| SMILES |
ClC1=CN=C(C)C(=C1)NCC1=CC=C(C(N[C@@H](C(NC2CC2)=O)CC2CCCC2)=O)S1
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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 : ~200 mg/mL (~433.82 mM; with ultrasonication)
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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 | 2.1691 mL | 10.8455 mL | 21.6910 mL | |
| 5 mM | 0.4338 mL | 2.1691 mL | 4.3382 mL | |
| 10 mM | 0.2169 mL | 1.0846 mL | 2.1691 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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