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Chemical Structure| 1404456-53-6 Chemical Structure| 1404456-53-6

Structure of GSK 2830371
CAS No.: 1404456-53-6

Chemical Structure| 1404456-53-6

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GSK 2830371 is a highly selective Wip1 phosphatase inhibitor with an IC50 of 6 nM.

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Product Details of GSK 2830371

CAS No. :1404456-53-6
Formula : C23H29ClN4O2S
M.W : 461.02
SMILES Code : ClC1=CN=C(C)C(NCC2=CC=C(C(N[C@@H](CC3CCCC3)C(NC4CC4)=O)=O)S2)=C1
MDL No. :MFCD28009442
InChI Key :IVDUVEGCMXCMSO-FQEVSTJZSA-N
Pubchem ID :70983932

Safety of GSK 2830371

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
IMR-32 50 μM 0–8 hours GSK2830371 increased p53 activity and induced Chk2/p53-mediated apoptosis in p53 wild-type NB cells, but not in the p53 mutant SK-N-AS cell line. PMC5171816
SH-SY5Y 50 μM 0–8 hours GSK2830371 increased p53 activity and induced Chk2/p53-mediated apoptosis in p53 wild-type NB cells, but not in the p53 mutant SK-N-AS cell line. PMC5171816
SK-N-AS 50 μM 0–8 hours GSK2830371 did not significantly increase p53 activity in the p53 mutant SK-N-AS cell line. PMC5171816
MV-4-11 5, 10, 20 µM 24, 48, 72 h WIP1i significantly reduced MV-4-11 cell viability, with a 78.2% reduction at 20 μM after 72 h PMC8067413
MOLM-13 5, 10, 20 µM 24, 48, 72 h WIP1i did not significantly affect MOLM-13 cell viability PMC8067413
OCI-AML3 5, 10, 20 µM 24, 48, 72 h WIP1i significantly reduced OCI-AML3 cell viability, with a 57.6% reduction at 20 μM after 72 h PMC8067413
NOMO-1 5, 10, 20 µM 24, 48, 72 h WIP1i did not significantly affect NOMO-1 cell viability PMC8067413
HEL 5, 10, 20 µM 24, 48, 72 h WIP1i did not significantly affect HEL cell viability PMC8067413
KASUMI-1 5, 10, 20 µM 24, 48, 72 h WIP1i did not significantly affect KASUMI-1 cell viability PMC8067413
HCT116+/+ 2.5μM 4 hours GSK2830371 induced degradation of full-length and truncated WIP1 PMC4785723
U2OS 2.5μM 4 hours GSK2830371 induced degradation of full-length and truncated WIP1 PMC4785723
DIPG7 cells 5 μM 48 hours GSK2830371 significantly reduced proliferation of DIPG7 cells. PMC6556861
DIPG VI-PPM1D-L513* cells 5 μM 48 hours GSK2830371 significantly reduced proliferation of DIPG VI-PPM1D-L513* cells. PMC6556861
secondary follicles 0, 0.1, 1.0, 5.0, 10.0 μM 6 days Inhibition of WIP1 phosphatase activity impairs follicular development and oocyte quality. PMC9736686
RBE 2.5 µM 72 and 96 hours GSK2830371 significantly enhanced the growth inhibitory activity of RG7388, evidenced by increased growth inhibition and cytotoxicity. PMC9548005
SK-Hep-1 2.5 µM 72 and 96 hours GSK2830371 significantly enhanced the growth inhibitory activity of RG7388, evidenced by increased growth inhibition and cytotoxicity. PMC9548005
A375 2.5 µM 72 hours GSK2830371 potentiated the growth-inhibitory and clonogenic cell killing effects of MDM2 inhibitors in p53WT but not p53MUT melanoma cells, indicating the potentiation worked in a p53-dependent manner. PMC5830592
WM35 2.5 µM 72 hours GSK2830371 potentiated the growth-inhibitory and clonogenic cell killing effects of MDM2 inhibitors in p53WT but not p53MUT melanoma cells, indicating the potentiation worked in a p53-dependent manner. PMC5830592
C8161 2.5 µM 72 hours GSK2830371 potentiated the growth-inhibitory and clonogenic cell killing effects of MDM2 inhibitors in p53WT but not p53MUT melanoma cells, indicating the potentiation worked in a p53-dependent manner. PMC5830592
MES-SA 2.5 µM 72 hours GSK2830371 significantly potentiated the growth inhibitory effects of RG7388 and HDM201, significantly reducing GI50 values. PMC8750798
SK-UT-1 2.5 µM 72 hours GSK2830371 did not show significant growth inhibitory effects in p53-mutant SK-UT-1 cells. PMC8750798
MCF-7 2.5μM 8 hours GSK2830371 induced WIP1 degradation, p53 stabilization, and increased p53Ser15 phosphorylation PMC4785723
MCF-10A cells 0.5μM GSK2830371 induced p38 and Hsp27 phosphorylation in MCF-10A cells and reversed Her2-induced disseminating phenotypes and activation and nuclear translocation of β-catenin. PMC7541706
MMTV-Her2 cells 0.5μM GSK2830371 upregulated phosphorylation of p38, MK2 and Hsp27-Ser86 and downregulated the levels of the Src phosphorylated and the active forms of β-catenin, increased E-cadherin junctions in organoids, and reduced percentage of invasive organoids in MMTV-Her2 cells. PMC7541706

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NSG mice DIPG7 cells orthotopic xenograft model brainstem injection 5 μM single dose, observed until symptomatic GSK2830371 significantly extended the survival of NSG mice xenografted with DIPG7 cells, suppressed tumor proliferation, and increased apoptosis. PMC6556861
Mice C57BL/6j Oral 7.5 mg/kg, 15 mg/kg twice daily for 14 days Inhibition of WIP1 phosphatase activity induces irregular estrous cycles, fertility declines, and decreased ovarian reserve through triggering excessive follicular atresia and primordial follicle activation. PMC9736686
NOD/SCID mice SK-Hep-1 xenograft model Oral gavage 75 mg/kg twice daily for two weeks The combination of GSK2830371 and RG7388 significantly inhibited tumor growth, with the combination treatment group showing a significant reduction in tumor volume and weight compared to the monotherapy groups. PMC9548005
Nude mice Orthotopic xenograft NB mouse model Intraperitoneal injection 25 mg/kg Once daily for 21 days GSK2830371 significantly inhibited neuroblastoma growth and induced Chk2/p53-mediated apoptosis in vivo. PMC5171816

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.17mL

0.43mL

0.22mL

10.85mL

2.17mL

1.08mL

21.69mL

4.34mL

2.17mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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