Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, is a master regulator of neural progenitor homeostasis, integrating multiple proliferation, and differentiation signals, and thus has been focused on as a potential target in neuroblastoma. 9-ING-41, a potent and selective small-molecule GSK-3 inhibitor, is active in neuroblastoma. In cell viability assay, 9-ING-41 inhibited the growth of SK-N-DZ and SK-N-BE(2) neuroblastoma cells with GI50s among 50–100 nM. 9-ING-41 (0.1–1 µM) inhibited GSK-3 leading to a decreased expression of the NF-κB target XIAP and significant apoptosis in neuroblastoma cells[1]. Teretment with low doses of 9-ING-41 for 48 hours specifically induced lymphoma cell apoptosis without affecting normal lymphocytes[2]. In vivo, 9-ING-41 (70 mg/kg) potentiated the effects of CPT-11 (5 mg/kg) in growth inhibition of neuroblastoma xenograft tumors[1].
9-ING-41 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MCF10A
0.5 μM
72 h
No significant effect on the growth of non-tumorigenic mammary epithelial cells
Cancer Lett. 2016 Oct 1;380(2):384-392
MDA-MB-231/LM2-4
2 μM
72 h
Inhibition of GSK-3 activity, reducing breast cancer cell survival
Cancer Lett. 2016 Oct 1;380(2):384-392
SKBR3
0.25 μM
72 h
Inhibition of GSK-3 activity, reducing breast cancer cell survival
Cancer Lett. 2016 Oct 1;380(2):384-392
MDA-MB-468
0.5 μM
72 h
Inhibition of GSK-3 activity, reducing breast cancer cell survival
Cancer Lett. 2016 Oct 1;380(2):384-392
HH cells
1-5 µM
72 h
Assess cell viability and induce apoptosis, results showed Elraglusib reduced cell viability and induced apoptosis
Cell Commun Signal. 2023 Jun 14;21(1):131.
Karpas-299 cells
1-5 µM
72 h
Assess cell viability and induce apoptosis, results showed Elraglusib reduced cell viability and induced apoptosis
Cell Commun Signal. 2023 Jun 14;21(1):131.
HS-Sultan cells
1-5 µM
72 h
Assess cell viability and induce apoptosis, results showed Elraglusib reduced cell viability and induced apoptosis
Cell Commun Signal. 2023 Jun 14;21(1):131.
Renal cancer cell line KU19-20
0.5-50 µM
96 h
9-ING-41 alone induced cell cycle arrest and apoptosis, and inhibited the proliferation of renal cancer cells.
Int J Mol Med. 2020 Feb;45(2):315-323
Renal cancer cell line KRCY
0.5-50 µM
96 h
9-ING-41 alone induced cell cycle arrest and apoptosis, and inhibited the proliferation of renal cancer cells.
Int J Mol Med. 2020 Feb;45(2):315-323
Renal cancer cell line Caki-1
0.5-50 µM
96 h
9-ING-41 alone induced cell cycle arrest and apoptosis, and inhibited the proliferation of renal cancer cells.
Int J Mol Med. 2020 Feb;45(2):315-323
Renal cancer cell line ACHN
0.5-50 µM
96 h
9-ING-41 alone induced cell cycle arrest and apoptosis, and inhibited the proliferation of renal cancer cells.
Int J Mol Med. 2020 Feb;45(2):315-323
SW480 cells
2 μM
3 h
Evaluate the effect of 9-ING-41 on SW480 cell growth; results showed SW480 cells were resistant to pure 9-ING-41, but the growth inhibitory effect of the combination of 5-FU and oxaliplatin was more pronounced in the presence of 9-ING-41
Front Pharmacol. 2021 Dec 9;12:777114
RKO cells
2 μM
3 h
Evaluate the effect of 9-ING-41 on RKO cell growth; results showed RKO cells were sensitive to 9-ING-41, and it significantly enhanced the growth inhibitory effect of 5-FU and oxaliplatin
Front Pharmacol. 2021 Dec 9;12:777114
HT-29 cells
2 μM
3 h
Evaluate the effect of 9-ING-41 on HT-29 cell growth; results showed HT-29 cells were resistant to transient inhibition of GSK-3β by 9-ING-41
Front Pharmacol. 2021 Dec 9;12:777114
CD8+ T cells
1 µM
48 h
To evaluate the effect of 9-ING-41 on cytokine secretion by CD8+ T cells. Results showed increased secretion of IFN-γ, granzyme B, and TRAIL, and decreased concentrations of VEGF, TNF-alpha, and CCL5/RANTES.
Cancer Biol Ther. 2022 Dec 31;23(1):417-423
STS cell lines
0.1 to 0.6 µM
72 h
To examine the antitumor effect of 9-ING-41 on STS, results showed that 9-ING-41 significantly suppressed the viability of all 20 STS cell lines by inhibiting GSK3β
J Hematol Oncol. 2021 Dec 2;14(1):202
9-ING-41 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NSG mice
BC-1 and BC-2 PDX models
Intraperitoneal injection
70 mg/kg
Twice weekly for four weeks
Enhanced the antitumor effect of CPT-11, leading to tumor regression
Cancer Lett. 2016 Oct 1;380(2):384-392
NSG mice
IB115 liposarcoma model
Intraperitoneal injection
70 mg/kg
Two injections, until day 38
To evaluate the in vivo antitumor effect of 9-ING-41 alone or in combination with chemotherapy, results showed that the combination treatment significantly reduced tumor volume
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