product name KX2-391
Description: KX2-391, also known as KXO1, is the first clinical peptidomimetic Src inhibitor that targets the peptide substrate site of Src, with GI50 of 9-60 nM in cancer cell lines. KX2-391 is an orally bioavailable small molecule with potential antineoplastic activity. Unlike other Src kinase inhibitors which bind to the ATP-binding site, Src kinase inhibitor KX2-391 specifically binds to the peptide substrate binding site of Src kinase; inhibition of kinase activity may result in the inhibition of primary tumor growth and the suppression of metastasis. Src tyrosine kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis.
References: Dig Dis Sci. 2009 Jul;54(7):1465-74; Eur J Med Chem. 2011 Oct;46(10):4853-8.
431.53
Formula
C26H29N3O3
CAS No.
897016-82-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 86 mg/mL (199.3 mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL (3.8 mM)
Solubility (In vivo)
4% DMSO+30% PEG 300+ddH2O: 5 mg/mL
Synonyms
KXO1
other peoduct :
| In Vitro |
In vitro activity: KX2-391 is a Src inhibitor that is directed to the Src substrate pocket. KX2-391 shows steep dose-response curves against Huh7 (GI 50 = 9 nM), PLC/PRF/5 (GI 50 = 13 nM), Hep3B (GI 50 = 26 nM), and HepG2 (GI 50 = 60 nM), four hepatic cell cancer (HCC) cell lines. KX2-391 is found to inhibit certain leukemia cells that are resistant to current commercially available drugs, such as those derived from chronic leukemia cells with the T3151 mutation. KX2-391 is evaluated in engineered Src driven cell growth assays inNIH3T3/c-Src527F and SYF/c-Src527F cells and exhibits GI50 with 23 nM and 39 nM, respectively. Kinase Assay: Cell Assay: Liver cell lines including Huh7, PLC/PRF/5, Hep3B, and HepG2 (NutriCyte, Buffalo, NY) are routinely cultured and maintained in basal medium containing 2% fetal bovine serum (FBS) at 37 °C and 5% CO2. Cells are seeded at 4.0 × 103/190 μL and 8.0 × 103/190 μL per well of 96-well plate in basal medium containing 1.5% FBS. These are cultured overnight at 37 °C and 5% CO2 prior to the addition of KX2-391, at concentrations ranging from 6,564 to 0.012 nM in triplicates. Treated cells are incubated for 3 days. Ten microliters of 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution (5 mg/mL) is then added to each well on day 3 and cells incubated for 4 hours. The formazan product is dissolved with 10% SDS in dilute HCl. Optical density at 570 nm is measured by using BioTek Synergy HT multiplatform microplate reader. For comparison of activity and potency, parallel experiments are performed using KX2-391. Growth inhibition curves, 50% inhibition concentration (GI50), and 80% inhibition concentration (GI80) are determined using GraphPad Prism 5 statistical software. Data are normalized to represent percentage of maximum response as well as reported in optical density at wavelength of 570 nm (OD570) signal format. |
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| In Vivo | In pre-clinical animal models of cancer, orally administered KX2-391 is shown to inhibit primary tumor growth and to suppress metastasis. |
| Animal model | |
| Formulation & Dosage | |
| References | Dig Dis Sci. 2009 Jul;54(7):1465-74; Eur J Med Chem. 2011 Oct;46(10):4853-8. |
