Synonym
9-ING-41; 9 ING 41; 9ING41; Elraglusib;
IUPAC/Chemical Name
3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-[1,3]dioxolo[4,5-f]indol-7-yl)-1H-pyrrole-2,5-dione
InChi Key
FARXPFGGGGLENU-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H13FN2O5/c1-25-7-13(11-5-17-18(6-15(11)25)30-9-29-17)19-20(22(27)24-21(19)26)14-8-28-16-3-2-10(23)4-12(14)16/h2-8H,9H2,1H3,(H,24,26,27)
SMILES Code
CN(C1=C2C=C3C(OCO3)=C1)C=C2C4=C(C5=COC6=C5C=C(F)C=C6)C(NC4=O)=O
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
Slightly 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
Biological target:
9-ING-41 is a maleimide-based ATP-competitive and selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 0.71 μM.
In vitro activity:
9-ING-41 was tested in T24, HT1376 and RT4 bladder cancer cell lines. 9-ING-41 treatment resulted in a decreased growth of bladder cancer cells at 0.25–1 μM concentrations in a dose-dependent manner with GI50 range of 0.4–0.5 μM (Fig. 1A). Moreover,a cytotoxic effect of 9-ING-41 was found in RT4 bladder cancer cells at >0.5 μM concentrations of 9-ING-41 (Fig. 1A). Cell cycle blockage was found at G2/M after 24 hours of 9-ING-41 treatment (Fig. 1C), suggesting that GSK-3 inactivation by 9-ING-41 halts progression of mitosis in bladder cancer cells. To investigate the mechanistic effect of GSK-3 inhibitor 9-ING-41 in the blockage of cell cycle in bladder cancer cells, the expression of G2/M regulatory proteins Cdk1 and Cyclin B1 was examined in 9-ING-41-treated cells. It was found that expression of Cdk1 and Cyclin B1 proteins was significantly decreased in 9-ING-41-treated bladder cancer cells (Fig. 2A). Moreover, treatment with 9-ING-41 led to a decreased expression of antiapoptotic molecules, Bcl-2 and XIAP, resulted in an increased apoptosis as shown by PARP cleavage in bladder cancer cells (Fig. 2A,B). Furthermore, caspase activation assay was used to demonstrate that 9-ING-41 treatment induces apoptotic cell death in bladder cancer cells (Fig. 2C). These in vitro results suggest that treatment with GSK-3 inhibitor 9-ING-41 suppresses expression of G2/M regulatory proteins and antiapoptotic molecules leading to cell cycle arrest and apoptosis in bladder cancer cells, and identify 9-ING-41 as a candidate for the targeted therapy of human bladder cancer.
Sci Rep. 2019; 9: 19977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934761/
In vivo activity:
In these studies, 9-ING-41 treatment was initiated 7 days after instillation of the adenoviral vectors. 9-ING-41 significantly improved decrements (p < 0.05) in lung compliance and lung volume compared to TGF-β adenoviral treated mice (Fig. 6A). Lung injury by morphometry was next analyzed using a 3-point scale, where 1 = no scarring and 3 = extensive scarring. 9-ING-41 treatment significantly reduced the lung injury score of TGF-β adenovirus induced PF in mice (Fig. 6B, p = 0.02). Collagen deposition (Fig. 6C) was likewise significantly reduced by 9-ING-41 treatment (Fig. 6C, p = 0.03). TGF-β adenovirus treated mice also demonstrated significantly increased numbers of apoptotic cells compared to GFP adenovirus controls. 9-ING-41 treatment significantly reduced the number of apoptotic cells, presumably including alveolar epithelial cells, in TGF-β treated mice compared to GFP adenoviral controls (Fig. 6D). While DMSO treated mice showed pronounced injury and areas of intense collagen deposition, 9-ING-41 treated mice had significantly fewer areas of injury and demonstrated less collagen deposition (Fig. 7B). These findings strongly support the hypothesis that the therapeutic targeting of GSK-3β with the novel inhibitor, 9-ING-41, reduces myofibroblast differentiation, collagen deposition, and subsequent PF in vivo.
Sci Rep. 2019; 9: 18925. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908609/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
5.0 |
0.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
404.35
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. Karmali R, Chukkapalli V, Gordon LI, Borgia JA, Ugolkov A, Mazar AP, Giles FJ. GSK-3β inhibitor, 9-ING-41, reduces cell viability and halts proliferation of B-cell lymphoma cell lines as a single agent and in combination with novel agents. Oncotarget. 2017 Nov 11;8(70):114924-114934. doi: 10.18632/oncotarget.22414. PMID: 29383130; PMCID: PMC5777742. 2. Kuroki H, Anraku T, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar AP, Giles FJ, Ugolkov A, Tomita Y. 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977. doi: 10.1038/s41598-019-56461-4. PMID: 31882719; PMCID: PMC6934761.
3. .Ugolkov AV, Bondarenko GI, Dubrovskyi O, Berbegall AP, Navarro S, Noguera R, O'Halloran TV, Hendrix MJ, Giles FJ, Mazar AP. 9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma. Anticancer Drugs. 2018 Sep;29(8):717-724. doi: 10.1097/CAD.0000000000000652. PMID: 29846250; PMCID: PMC6092218.
4. Jeffers A, Qin W, Owens S, Koenig KB, Komatsu S, Giles FJ, Schmitt DM, Idell S, Tucker TA. Glycogen Synthase Kinase-3β Inhibition with 9-ING-41 Attenuates the Progression of Pulmonary Fibrosis. Sci Rep. 2019 Dec 12;9(1):18925. doi: 10.1038/s41598019-55176-w. PMID: 31831767; PMCID: PMC6908609.
In vitro protocol:
1. Karmali R, Chukkapalli V, Gordon LI, Borgia JA, Ugolkov A, Mazar AP, Giles FJ. GSK-3β inhibitor, 9-ING-41, reduces cell viability and halts proliferation of B-cell lymphoma cell lines as a single agent and in combination with novel agents. Oncotarget. 2017 Nov 11;8(70):114924-114934. doi: 10.18632/oncotarget.22414. PMID: 29383130; PMCID: PMC5777742. 2. Kuroki H, Anraku T, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar AP, Giles FJ, Ugolkov A, Tomita Y. 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977. doi: 10.1038/s41598-019-56461-4. PMID: 31882719; PMCID: PMC6934761.
In vivo protocol:
1. .Ugolkov AV, Bondarenko GI, Dubrovskyi O, Berbegall AP, Navarro S, Noguera R, O'Halloran TV, Hendrix MJ, Giles FJ, Mazar AP. 9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma. Anticancer Drugs. 2018 Sep;29(8):717-724. doi: 10.1097/CAD.0000000000000652. PMID: 29846250; PMCID: PMC6092218.
2. Jeffers A, Qin W, Owens S, Koenig KB, Komatsu S, Giles FJ, Schmitt DM, Idell S, Tucker TA. Glycogen Synthase Kinase-3β Inhibition with 9-ING-41 Attenuates the Progression of Pulmonary Fibrosis. Sci Rep. 2019 Dec 12;9(1):18925. doi: 10.1038/s41598019-55176-w. PMID: 31831767; PMCID: PMC6908609.
1: Karmali R, Chukkapalli V, Gordon LI, Borgia JA, Ugolkov A, Mazar AP, Giles FJ. GSK-3β inhibitor, 9-ING-41, reduces cell viability and halts proliferation of B-cell lymphoma cell lines as a single agent and in combination with novel agents. Oncotarget. 2017 Nov 11;8(70):114924-114934. doi: 10.18632/oncotarget.22414. eCollection 2017 Dec 29. PubMed PMID: 29383130; PubMed Central PMCID: PMC5777742.
2: Ugolkov A, Qiang W, Bondarenko G, Procissi D, Gaisina I, James CD, Chandler J, Kozikowski A, Gunosewoyo H, O'Halloran T, Raizer J, Mazar AP. Combination Treatment with the GSK-3 Inhibitor 9-ING-41 and CCNU Cures Orthotopic Chemoresistant Glioblastoma in Patient-Derived Xenograft Models. Transl Oncol. 2017 Aug;10(4):669-678. doi: 10.1016/j.tranon.2017.06.003. Epub 2017 Jun 30. PubMed PMID: 28672195; PubMed Central PMCID: PMC5496477.
3: Ugolkov A, Gaisina I, Zhang JS, Billadeau DD, White K, Kozikowski A, Jain S, Cristofanilli M, Giles F, O'Halloran T, Cryns VL, Mazar AP. GSK-3 inhibition overcomes chemoresistance in human breast cancer. Cancer Lett. 2016 Oct 1;380(2):384-92. doi: 10.1016/j.canlet.2016.07.006. Epub 2016 Jul 14. PubMed PMID: 27424289; PubMed Central PMCID: PMC5786372.
4: Pal K, Cao Y, Gaisina IN, Bhattacharya S, Dutta SK, Wang E, Gunosewoyo H, Kozikowski AP, Billadeau DD, Mukhopadhyay D. Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer. Mol Cancer Ther. 2014 Feb;13(2):285-96. doi: 10.1158/1535-7163.MCT-13-0681. Epub 2013 Dec 10. PubMed PMID: 24327518; PubMed Central PMCID: PMC3956125.
