WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H540187
CAS#: 1404456-53-6
Description: GSK 2830371 is a WiP1 inhibitor. It inhibits cell growth and tumor growth in lymphoma and neuroblastoma models.
Hodoodo Cat#: H540187
Name: GSK-2830371
CAS#: 1404456-53-6
Chemical Formula: C23H29ClN4O2S
Exact Mass: 460.17
Molecular Weight: 461.021
Elemental Analysis: C, 59.92; H, 6.34; Cl, 7.69; N, 12.15; O, 6.94; S, 6.95
Synonym: GSK 2830371; GSK2830371; GSK-2830371.
IUPAC/Chemical Name: (S)-5-(((5-chloro-2-methylpyridin-3-yl)amino)methyl)-N-(3-cyclopentyl-1-(cyclopropylamino)-1-oxopropan-2-yl)thiophene-2-carboxamide
InChi Key: IVDUVEGCMXCMSO-FQEVSTJZSA-N
InChi Code: InChI=1S/C23H29ClN4O2S/c1-14-19(11-16(24)12-25-14)26-13-18-8-9-21(31-18)23(30)28-20(10-15-4-2-3-5-15)22(29)27-17-6-7-17/h8-9,11-12,15,17,20,26H,2-7,10,13H2,1H3,(H,27,29)(H,28,30)/t20-/m0/s1
SMILES Code: O=C(C1=CC=C(CNC2=CC(Cl)=CN=C2C)S1)N[C@@H](CC3CCCC3)C(NC4CC4)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | GSK 2830371 is a highly selective Wip1 phosphatase inhibitor with IC50 of 6 nM. |
| In vitro activity: | Novel Wip1 inhibitor GSK2830371 induced Chk2/p53-mediated apoptosis in NB cells in a p53-dependent manner. In addition, GSK2830371 suppressed the colony-formation potential of p53 wild-type NB cell lines. Reference: Mol Cancer Ther. 2016 Mar;15(3):379-91. https://pubmed.ncbi.nlm.nih.gov/26832796/ |
| In vivo activity: | Treatment of tumor cells with the inhibitor GSK2830371 increases phosphorylation of Wip1 substrates and causes growth inhibition in both hematopoietic tumor cell lines and Wip1-amplified breast tumor cells harboring wild-type TP53. Oral administration of Wip1 inhibitors in mice results in expected pharmacodynamic effects and causes inhibition of lymphoma xenograft growth. Reference: Nat Chem Biol. 2014 Mar;10(3):181-7. https://pubmed.ncbi.nlm.nih.gov/24390428/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 65.07 | |
| DMF:PBS (pH 7.2) (1:5) | 0.1 | 0.22 | |
| DMSO | 53.5 | 116.10 | |
| Ethanol | 46.7 | 101.26 |
The following data is based on the product molecular weight 461.02 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Wu CE, Huang CY, Chen CP, Pan YR, Chang JW, Chen JS, Yeh CN, Lunec J. WIP1 Inhibition by GSK2830371 Potentiates HDM201 through Enhanced p53 Phosphorylation and Activation in Liver Adenocarcinoma Cells. Cancers (Basel). 2021 Jul 31;13(15):3876. doi: 10.3390/cancers13153876. PMID: 34359777; PMCID: PMC8345393. 2. Chen Z, Wang L, Yao D, Yang T, Cao WM, Dou J, Pang JC, Guan S, Zhang H, Yu Y, Zhao Y, Wang Y, Xu X, Shi Y, Patel R, Zhang H, Vasudevan SA, Liu S, Yang J, Nuchtern JG. Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis. Sci Rep. 2016 Dec 19;6:38011. doi: 10.1038/srep38011. PMID: 27991505; PMCID: PMC5171816. 3. Gilmartin AG, Faitg TH, Richter M, Groy A, Seefeld MA, Darcy MG, Peng X, Federowicz K, Yang J, Zhang SY, Minthorn E, Jaworski JP, Schaber M, Martens S, McNulty DE, Sinnamon RH, Zhang H, Kirkpatrick RB, Nevins N, Cui G, Pietrak B, Diaz E, Jones A, Brandt M, Schwartz B, Heerding DA, Kumar R. Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat Chem Biol. 2014 Mar;10(3):181-7. doi: 10.1038/nchembio.1427. Epub 2014 Jan 5. PMID: 24390428. |
| In vitro protocol: | 1. Wu CE, Huang CY, Chen CP, Pan YR, Chang JW, Chen JS, Yeh CN, Lunec J. WIP1 Inhibition by GSK2830371 Potentiates HDM201 through Enhanced p53 Phosphorylation and Activation in Liver Adenocarcinoma Cells. Cancers (Basel). 2021 Jul 31;13(15):3876. doi: 10.3390/cancers13153876. PMID: 34359777; PMCID: PMC8345393. 2. Chen Z, Wang L, Yao D, Yang T, Cao WM, Dou J, Pang JC, Guan S, Zhang H, Yu Y, Zhao Y, Wang Y, Xu X, Shi Y, Patel R, Zhang H, Vasudevan SA, Liu S, Yang J, Nuchtern JG. Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis. Sci Rep. 2016 Dec 19;6:38011. doi: 10.1038/srep38011. PMID: 27991505; PMCID: PMC5171816. |
| In vivo protocol: | 1. Gilmartin AG, Faitg TH, Richter M, Groy A, Seefeld MA, Darcy MG, Peng X, Federowicz K, Yang J, Zhang SY, Minthorn E, Jaworski JP, Schaber M, Martens S, McNulty DE, Sinnamon RH, Zhang H, Kirkpatrick RB, Nevins N, Cui G, Pietrak B, Diaz E, Jones A, Brandt M, Schwartz B, Heerding DA, Kumar R. Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat Chem Biol. 2014 Mar;10(3):181-7. doi: 10.1038/nchembio.1427. Epub 2014 Jan 5. PMID: 24390428. |
1: Richter M, Dayaram T, Gilmartin AG, Ganji G, Pemmasani SK, Van Der Key H, Shohet JM, Donehower LA, Kumar R. WIP1 phosphatase as a potential therapeutic target in neuroblastoma. PLoS One. 2015 Feb 6;10(2):e0115635. doi: 10.1371/journal.pone.0115635. eCollection 2015. PubMed PMID: 25658463; PubMed Central PMCID: PMC4319922.
2: Sriraman A, Radovanovic M, Wienken M, Najafova Z, Li Y, Dobbelstein M. Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity. Oncotarget. 2016 May 31;7(22):31623-38. doi: 10.18632/oncotarget.9302. PubMed PMID: 27183917; PubMed Central PMCID: PMC5077964.
3: Kojima K, Maeda A, Yoshimura M, Nishida Y, Kimura S. The pathophysiological significance of PPM1D and therapeutic targeting of PPM1D-mediated signaling by GSK2830371 in mantle cell lymphoma. Oncotarget. 2016 Oct 25;7(43):69625-69637. doi: 10.18632/oncotarget.11904. PubMed PMID: 27626308; PubMed Central PMCID: PMC5342503.
4: Esfandiari A, Hawthorne TA, Nakjang S, Lunec J. Chemical Inhibition of Wild-Type p53-Induced Phosphatase 1 (WIP1/PPM1D) by GSK2830371 Potentiates the Sensitivity to MDM2 Inhibitors in a p53-Dependent Manner. Mol Cancer Ther. 2016 Mar;15(3):379-91. doi: 10.1158/1535-7163.MCT-15-0651. Epub 2016 Feb 1. PubMed PMID: 26832796; PubMed Central PMCID: PMC4785723.
5: Chen Z, Wang L, Yao D, Yang T, Cao WM, Dou J, Pang JC, Guan S, Zhang H, Yu Y, Zhao Y, Wang Y, Xu X, Shi Y, Patel R, Zhang H, Vasudevan SA, Liu S, Yang J, Nuchtern JG. Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis. Sci Rep. 2016 Dec 19;6:38011. doi: 10.1038/srep38011. PubMed PMID: 27991505; PubMed Central PMCID: PMC5171816.
6: Gilmartin AG, Faitg TH, Richter M, Groy A, Seefeld MA, Darcy MG, Peng X, Federowicz K, Yang J, Zhang SY, Minthorn E, Jaworski JP, Schaber M, Martens S, McNulty DE, Sinnamon RH, Zhang H, Kirkpatrick RB, Nevins N, Cui G, Pietrak B, Diaz E, Jones A, Brandt M, Schwartz B, Heerding DA, Kumar R. Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat Chem Biol. 2014 Mar;10(3):181-7. doi: 10.1038/nchembio.1427. Epub 2014 Jan 5. PubMed PMID: 24390428.
7: Pechackova S, Burdova K, Benada J, Kleiblova P, Jenikova G, Macurek L. Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3. Oncotarget. 2016 Mar 22;7(12):14458-75. doi: 10.18632/oncotarget.7363. PubMed PMID: 26883108; PubMed Central PMCID: PMC4924728.
