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

• ChemBase ID: 73177
• Molecular Formular: C26H29N3O3
• Molecular Mass: 431.52676
• Monoisotopic Mass: 431.2208918
• SMILES: c1c(ccc(c1)c1ccc(nc1)CC(=O)NCc1ccccc1)OCCN1CCOCC1
• Canonical SMILES: O=C(Cc1ccc(cn1)c1ccc(cc1)OCCN1CCOCC1)NCc1ccccc1
• InChI: InChI=1S/C26H29N3O3/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29/h1-11,20H,12-19H2,(H,28,30)
• InChIKey: HUNGUWOZPQBXGX-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-benzyl-2-(5-{4-[2-(morpholin-4-yl)ethoxy]phenyl}pyridin-2-yl)acetamide
• IUPAC Traditional name: N-benzyl-2-(5-{4-[2-(morpholin-4-yl)ethoxy]phenyl}pyridin-2-yl)acetamide
• Synonyms: KX2-391

Database IDs

• CAS Number: 897016-82-9
• PubChem SID: 162038097
• PubChem CID: 23635314

CALCULATED PROPERTIES

• Acid pKa: 15.356042
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 2.0425603
• LogD (pH = 7.4): 3.1422613
• Log P: 3.2100768
• Molar Refractivity: 124.8612 cm^3
• Polarizability: 49.939484 Å^3
• Polar Surface Area: 63.69 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Src-bcr-Abl

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2700

Biological Activity

• Description: KX2-391 (KX01) is a highly selective non ATP-competitive Src inhibitor with GI50 of 9-60 nM in cancer cell lines .
• Targets:

  HuH7

  ;

  PLC/PRF/5

  ;

  Hep 3B

  ;

  Hep G2

• IC50:

  9 nM (GI50)

  ;

  13 nM (GI50)

  ;

  26 nM (GI50)

  ;

  60 nM (GI50) ^[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 (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. ^[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: In pre-clinical animal models of cancer, orally administered KX2-391 is shown to inhibit primary tumor growth and to suppress metastasis. ^[2]
• Clinical Trials: KX2-391 is in Phase 1 clinical trial for evaluation of it in elderly subjects with acute myeloid leukemia (AML).

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: Huh7, PLC/PRF/5, Hep3B, and HepG2 cell lines
• Concentrations: 6,564 to 0.012 nM
• Incubation Time: 3 days
• Methods:

  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 × 10^3/190 μL and 8.0 × 10^3/190 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.

References

• References: [1] Lau GM, et al, Dig Dis Sci, 2009, 54(7), 1465-1474.
• References: [2] Fallah-Tafti A, et al, Eur J Med Chem, 2011, 46(10), 4853-4858.

REFERENCES

• Lau GM, et al, Dig Dis Sci, 2009, 54(7), 1465-1474.
• Fallah-Tafti A, et al, Eur J Med Chem, 2011, 46(10), 4853-4858.