LJI308pan-RSK inhibitor CAS# 1627709-94-7 |
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| Cas No. | 1627709-94-7 | SDF | Download SDF |
| PubChem ID | 118704762 | Appearance | Powder |
| Formula | C21H18F2N2O2 | M.Wt | 368.38 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 25 mg/mL (67.86 mM; Need ultrasonic) | ||
| Chemical Name | 2,6-difluoro-4-[4-(4-morpholin-4-ylphenyl)pyridin-3-yl]phenol | ||
| SMILES | C1COCCN1C2=CC=C(C=C2)C3=C(C=NC=C3)C4=CC(=C(C(=C4)F)O)F | ||
| Standard InChIKey | YUYJEQHNWKQNBT-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C21H18F2N2O2/c22-19-11-15(12-20(23)21(19)26)18-13-24-6-5-17(18)14-1-3-16(4-2-14)25-7-9-27-10-8-25/h1-6,11-13,26H,7-10H2 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | LJI308 is a new and potent pan-RSK inhibitor, with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.
IC50 value: 6/4/13 nM
Target: RSK1/2/3
in vitro: LJI308 efficiently inhibits RSK activity. LJI308 inhibites S6K1 with an IC50 of 0.8 μM, representing a 200-fold lower inhibition than that of RSK2. LJI308 inhibits MEK4 less than 50% at 10 μMand HIP kinase 1 less than 50% at 1 μM. [1] LJI308 inhibits the growth and survival of TNBC. LJI308 also suppresses the growth of HTRY-LT cells in 3-dimensional soft agar cultures. LJI308 is one of the first potent and effective targeted therapies for TNBC that, unlike currently utilized drugs, exhibits efficacy in eliminating the CSC population. [2] References: | |||||
LJI308 Dilution Calculator
LJI308 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.7146 mL | 13.5729 mL | 27.1459 mL | 54.2918 mL | 67.8647 mL |
| 5 mM | 0.5429 mL | 2.7146 mL | 5.4292 mL | 10.8584 mL | 13.5729 mL |
| 10 mM | 0.2715 mL | 1.3573 mL | 2.7146 mL | 5.4292 mL | 6.7865 mL |
| 50 mM | 0.0543 mL | 0.2715 mL | 0.5429 mL | 1.0858 mL | 1.3573 mL |
| 100 mM | 0.0271 mL | 0.1357 mL | 0.2715 mL | 0.5429 mL | 0.6786 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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IC50: 0.004 to 0.013 mM for RSK1, 2, and 3.
LJI308 is a potent and selective inhibitor of RSK. The p90 ribosomal S6 kinase (RSK) comprises a family of serine/threonine kinase which is expressed in various human cancers. RSK is the cytosolic substrate for the ERK (extracellular sianal-regulated kinase), involved in direct regulation of cell survival, proliferation, and cell polarity. Previous studies have demonstrated that RSK pathway is important for the growth and proliferation of cancer stem cells [1,2].
The IC50 values of LJI308 against RSK1, 2, and 3 were about 0.004 - 0.013 mmol/L. 10 μM LJI308 could bind to nearly 100% of the RSK2. LJI308 bound the N-termini of RSK1, RSK3, and RSK4 to a similar extent. LJI308 inhibited S6K1 with an IC50 of 0.8 mM. In both MDA-MB-231 and H358 cell lines, 1 μM and 10 μM LJI308 exihibited an inhibitory effect on colony formation and cell growth with a different sensitivity [1]. In HTRY-LT cell lines, treating with LJI308 (1-10 ?M) after 4 or 8 days decreased the cell viability by up to 90%; while little to no effect was observed in the non-tumorigenic HTRZ cells [2].
LJI308, the RSK inhibitor, could be used in combination with conventional chemotherapy to overcome the drug resistance and improve survival in patients with the triple-negative breast cancer (TNBC) [2].
References:
Aronchik I, Appleton B A, Basham S E, et al. Novel potent and selective inhibitors of p90 ribosomal S6 kinase reveal the heterogeneity of RSK function in MAPK-driven cancers[J]. Molecular Cancer Research, 2014, 12(5): 803-812.
Davies A H, Reipas K, Hu K, et al. Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells[J]. Oncotarget, 2015, 6(24): 20570.
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Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells.[Pubmed:26011941]
Oncotarget. 2015 Aug 21;6(24):20570-7.
The triple-negative breast cancer (TNBC) subtype is enriched in cancer stem cells (CSCs) and clinically correlated with the highest rate of recurrence. Several studies implicate the RSK pathway as being pivotal for the growth and proliferation of CSCs, which are postulated to drive tumor relapse. We now address the potential for the newly developed RSK inhibitor LJI308 to target the CSC population and repress TNBC growth and dissemination. Overexpression of the Y-box binding protein-1 (YB-1) oncogene in human mammary epithelial cells (HMECs) drove TNBC tumor formation characterized by a multi-drug resistance phenotype, yet these cells were sensitive to LJI308 in addition to the classic RSK inhibitors BI-D1870 and luteolin. Notably, LJI308 specifically targeted transformed cells as it had little effect on the non-tumorigenic parental HMECs. Loss of cell growth, both in 2D and 3D culture, was attributed to LJI308-induced apoptosis. We discovered CD44+/CD49f+ TNBC cells to be less sensitive to chemotherapy compared to the isogenic CD44-/CD49f- cells. However, inhibition of RSK using LJI308, BI-D1870, or luteolin was sufficient to eradicate the CSC population. We conclude that targeting RSK using specific and potent inhibitors, such as LJI308, delivers the promise of inhibiting the growth of TNBC.
