9-ING-41 is a glycogen synthase kinase-3 (GSK-3) inhibitor that induces apoptosis and cell cycle arrest at prophase by targeting centrosomes and microtubule-bound GSK-3β. 9-ING-41 has anticancer activity.
Physicochemical Properties
| Molecular Formula | C22H13FN2O5 |
| Molecular Weight | 404.347429037094 |
| Exact Mass | 404.081 |
| Elemental Analysis | C, 65.35; H, 3.24; F, 4.70; N, 6.93; O, 19.78 |
| CAS # | 1034895-42-5 |
| Related CAS # | 1034895-42-5 |
| PubChem CID | 44582816 |
| Appearance | Pink to red solid powder |
| LogP | 3.688 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 30 |
| Complexity | 802 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC1C=CC2=C(C=1)C(=CO2)C1C(NC(C=1C1=CN(C)C2C=C3C(=CC1=2)OCO3)=O)=O |
| 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) |
| 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 |
| Synonyms | 9-ING-41; 9 ING 41; 9ING41 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | GSK-3β (IC50 = 0.71 μM) |
| ln Vitro | 9-ING-41, a clinically relevant small molecule GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity, suppresses the growth of neuroblastoma cells.[1] 9-ING-41 induces apoptosis and cell cycle arrest at prophase by targeting centrosomes and microtubule-bound GSK3β.[2] |
| ln Vivo | In a mouse model of MCL, 9-ING-41 has antitumor activity as a single agent.[2] The combination of clinically relevant doses of CPT-11 and 9-ING-41 results in a greater antitumor effect than either agent alone, according to mouse xenograft studies. [1] |
| Cell Assay | Measurement of cell viability. Relative number of viable cancer cells is determined by measuring the optical density using CellTiter 96 Aqueous One Solution Cell Proliferation Assay kit according to the manufacturer’s instructions. GraphPad Prism 6.0 software is used to determine a GI50 value for each compound using a non-linear regression model with standard slope. |
| Animal Protocol |
6–8 week-old female athymic nude mice 70 mg/kg IP |
| References |
[1]. Anticancer Drugs . 2018 Sep;29(8):717-724. [2]. Blood . 2019 Jul 25;134(4):363-373. |
| Additional Infomation |
Elraglusib is under investigation in clinical trial NCT04218071 (Actuate 1901: 9-ING-41 in Myelofibrosis). Elraglusib is a maleimide-based, small molecule inhibitor of glycogen synthase kinase-3 (GSK-3; serine/threonine-protein kinase GSK3) with potential antineoplastic activity. Upon intravenous administration, elraglusib binds to and competitively inhibits GSK-3, which may lead to downregulation of nuclear factor kappa B (NF-kappaB) and decreased expression of NF-kappaB target genes including cyclin D1, B-cell lymphoma 2 (Bcl-2), anti-apoptotic protein XIAP, and B-cell lymphoma extra-large (Bcl-XL). This may inhibit NF-kappaB-mediated survival and chemoresistance in certain tumor types. GSK-3, a constitutively active serine/threonine kinase that plays a role in numerous pathways involved in protein synthesis, cellular proliferation, differentiation, and metabolism, is aberrantly overexpressed in certain tumor types and may promote tumor cell survival and resistance to chemotherapy and radiotherapy. |
Solubility Data
| Solubility (In Vitro) | DMSO: 50~81 mg/mL (123.7~200.3 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.18 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4731 mL | 12.3655 mL | 24.7310 mL | |
| 5 mM | 0.4946 mL | 2.4731 mL | 4.9462 mL | |
| 10 mM | 0.2473 mL | 1.2366 mL | 2.4731 mL |