Product Information
Applications
Biological Information
Primary TargetWip1/PPM1D/PP2Cδ
Primary Target IC<sub>50</sub>6 nM for dephosphorylation of fluorescein diphosphate by Wip1 (2-240) and 13 nM for phospho-p38 MAP kinase (Thr180)
Purity≥97% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage +2°C to +8°C
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications

Documentation

PPM1D Phosphatase Inhibitor II, GSK2830371 - Calbiochem SDS

Title

Safety Data Sheet (SDS) 

References

Reference overview
Gilmartin, A.G., et al. 2014. Nature Chem. Biol. 10, 181.
Data Sheet

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision27-June-2014 JSW
Synonyms(S)-5-((5-Chloro-2-methylpyridin-3-ylamino)methyl)-N-(3-cyclopentyl-1-(cyclopropylamino)-1-oxopropan-2-yl)thiophene-2-carboxamide, PP2Cδ Inhibitor II, Wip1 Inhibitor II, WT-53-Induced Phosphatase Inhibitor; GSK 2830371
DescriptionA cell-permeable pyridinylaminomethylthienylcarboxamide that acts as a potent inhibitor against wild-type p53-induced phosphatase Wip1/PPM1D/PP2Cδ activity (IC50/[wip1]/[substrate]= 6 nM/1 nM Wip1/50 µM FDP and 13 nM/15 nM Wip1/8 nM pT180 p38) via an allosteric interaction with the ′flap′ region outside the catalytic site in a reversible and substrate-noncompetitive manner, while exhibiting little potency toward yeast YopH and 22 other human phosphatases (IC50 >30 µM), including PPM1A/PP2Cα & PPM1K/PP2Cκ. Shown to increase cellular Wip1 substrates phosphorylation, including p53 (S15), Chk2 (T68), H2AX (S139), and ATM (S1981), leading to p53 response protein p21/Waf1 upregulation and selective growth inhibition against breast cancer MCF-7 (IC50 = 500 nM in 14-d colony formation assay) and 22 lymphoid cell lines (IC50 from 24 nM to 2.2 µM in 7-d viability assay) expressing wt p53, but not BT474 breast cancer or a panel of 25 hematologic cancer cultures with mutant p53 status (IC50 >10 µM). Albeit short in vivo half-life, frequent and high daily oral dosages effectively suppress B-cell lymphoma DoHH2-derived tumor growth in mice (by 41% and 68% in 14 days with 75 mg/kg/12 h or 150 mg/kg/8 h oral dosage, respectively) in vivo. In addition to direct inhibition against Wip1 phosphatase activity, GSK2830371 binding also results in downregulation of cellular Wip1 protein, but not mRNA, level due to ubiquitination-dependent degradation. MG-132 (Cat. Nos. 474790, 474787, 474788, and 474791) effectively prevents GSK2830371-induced Wip1 degradation without interfering with the phosphorylation enhancing effect of GSK2830371 toward Wip1 substrates.
FormLight yellow powder
Intert gas (Yes/No) Packaged under inert gas
Chemical formulaC₂₃H₂₉ClN₄O₂S
Purity≥97% by HPLC
SolubilityDMSO (100 mg/ml)
Storage +2°C to +8°C
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Toxicity Standard Handling
ReferencesGilmartin, A.G., et al. 2014. Nature Chem. Biol. 10, 181.

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Categories

Life Science Research > Inhibitors and Biochemicals > Small Molecules & Inhibitors > Protein Phosphorylation / Dephosphorylation