ALW-II-41-27 is a Eph receptor tyrosine kinase inhibitor with an IC50 of 11 nM for EPHA2. In H358 cells, treatment with ALW-II-41-27 at a concentration of 1 μM within 15 minutes impaired the tyrosine phosphorylation of the EPHA2 receptor and continued to inhibit the tyrosine phosphorylation through 6 hours. ALW-II-41-27 also dose-dependently inhibited the EPHA2 phosphorylation induced by ligand.
In mice bearing non–small cell lung cancers (NSCLCs), intraperitoneal injection with ALW-II-41-27 at a dose of 15 mg/kg twice daily for 14 days significantly resulted in an inhibition of the growth of H358 tumors. ALW-II-41-27 significantly increased the apoptosis of tumors compared with the vehicle alone or NG-25. This was similar to the effect of the genetic ablation of EPHA2. Compared with treatments with vehicle alone or NG-25, treatment with ALW-II-41-27 did not result in significant differences in the vessel density or proliferation of tumors.
Acta Pharmacol Sin. 2019 Jul 17.
EPHA2 feedback activation limits the response to PDEδ inhibition in KRAS-dependent cancer cells.
ALW-II-41-27 purchased from AbMole
|Cell lines||Non–small cell lung cancer (NSCLC) PC-9/ER, PC-9/ERC15, PC-9/ERC16 cell lines|
|Preparation method||Treatment with 1 μM ALW-II-41-27 inhibited cell proliferation and increased apoptosis in erlotinib-resistant NSCLC cell lines. Apoptosis induced by ALW-II-41-27 was accompanied by the increase of cleavage of caspase-3 and PARP as well as decreased expression of antiapoptotic proteins BCL-xL and MCL-1.|
|Incubation time||72 h|
|Animal models||6-week-old athymic nude mice|
|Dosages||15, 30 mg/kg, twice daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO: ≥ 30 mg/mL|
Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers.
Song W, et al. Oncogene. 2017 Oct 5;36(40):5620-5630. PMID: 28581527.
Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase.
Moccia M, et al. PLoS One. 2015 Jun 5;10(6):e0128364. PMID: 26046350.
Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC.
Amato KR, et al. J Clin Invest. 2014 May;124(5):2037-49. PMID: 24713656.
cGAMP is an endogenous second messenger in metazoans and triggers interferon production in response to cytosolic DNA.
N6-isopentenyladenosine is a plant hormone.
X-α-Gal is suitable as a substrate for α-galactosidase.
RU320521 (also known as RU521; RU.521) is a potent and selective inhibitor of cGAS, inhibiting cGAS-mediated interferon upregulation.
|Dextran sulfate sodium salt
Dextran sulfate sodium salt is a polyanionic derivative of dextran produced by esterification of Dextran with chlorosulphonic acid.
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