9-ING-41
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MedKoo CAT#: 562032

CAS#: 1034895-42-5

Description: 9-ING-41 is a glycogen synthase kinase-3 (GSK-3) inhibitor. 9-ING-41 leads to cell cycle arrest, autophagy and apoptosis in bladder cancer cells. 9-ING-41 enhanced the growth inhibitory effects of gemcitabine or cisplatin when used in combination in bladder cancer cells. 9-ING-41 sensitized bladder cancer cells to the cytotoxic effects of human immune effector cells.


Chemical Structure

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9-ING-41
CAS# 1034895-42-5

Theoretical Analysis

MedKoo Cat#: 562032
Name: 9-ING-41
CAS#: 1034895-42-5
Chemical Formula: C22H13FN2O5
Exact Mass: 404.0808
Molecular Weight: 404.35
Elemental Analysis: C, 65.35; H, 3.24; F, 4.70; N, 6.93; O, 19.78

Price and Availability

Size Price Availability Quantity
5.0mg USD 90.0 Ready to ship
10.0mg USD 165.0 Ready to ship
25.0mg USD 350.0 Ready to ship
50.0mg USD 550.0 Ready to ship
100.0mg USD 850.0 Ready to ship
200.0mg USD 1350.0 Ready to ship
500.0mg USD 1950.0 Ready to ship
1.0g USD 3350.0 Ready to ship
2.0g USD 5650.0 2 Weeks
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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

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

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 123.66

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.

Recalculate based on batch purity %
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.

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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.