KX2-391

Name

N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide

Synonym

Description

KX2-391 is an inhibitor of Src that targets the peptide substrate site of Src, with GI50 of 9-60 nM in cancer cell lines.

Related Catalog

Target

GI50: 9 nM (Src, in HuH7 cells), 13 nM (Src, in PLC/PRF/5 cells), 26 nM (Src, in Hep3B cells), 60 nM (Src, in HepG2 cells)[1]

In Vitro

KX2-391 is a Src inhibitor that is directed to the Src substrate pocket. KX2-391 shows steep dose-response curves against Huh7 (GI50=9 nM), PLC/PRF/5 (GI50=13 nM), Hep3B (GI50=26 nM), and HepG2 (GI50=60 nM), four hepatic cell cancer (HCC) cell lines[1]. 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[2].

In Vivo

Orally administered KX2-391 is shown to inhibit primary tumor growth and to suppress metastasis, in pre-clinical animal models of cancer[2].

Cell Assay

Liver cell lines including Huh7, PLC/PRF/5, Hep3B, and HepG2 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 μLs 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. 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[1].

References

[1]. Lau GM, et al. Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro. Dig Dis Sci, 2009, 54(7), 1465-1474.

[2]. Fallah-Tafti A, et al. Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, Src kinase inhibitory and anticancer activities. Eur J Med Chem, 2011, 46(10), 4853-4858.

Density

1.2±0.1 g/cm3

Boiling Point

680.9±55.0 °C at 760 mmHg

Molecular Formula

C26H29N3O3

Molecular Weight

431.527

Flash Point

365.6±31.5 °C

Exact Mass

431.220886

PSA

67.18000

LogP

1.97

Vapour Pressure

0.0±2.1 mmHg at 25°C

Index of Refraction

1.588

Precursor  2

 

• CAS#:1038395-64-0
  methyl 2-[5-[4-...
• CAS#:100-46-9
  Benzylamine

DownStream  0

 

KX2-391

N-Benzyl-2-(5-{4-[2-(4-morpholinyl)ethoxy]phenyl}-2-pyridinyl)acetamide

N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide

pound not KX2391 pound not KX2 391

UNII-4V9848RS5G

2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide

2-Pyridineacetamide, 5-[4-[2-(4-morpholinyl)ethoxy]phenyl]-N-(phenylmethyl)-

N-benzyl-2-{5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl}acetamide

cc-266