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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 Experiment | |
|---|---|
| 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. |
| Concentrations | 1 μM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | 6-week-old athymic nude mice |
| Formulation | |
| Dosages | 15, 30 mg/kg, twice daily |
| Administration | Intraperitoneal injection |
| Molecular Weight | 607.69 |
| Formula | C32H32F3N5O2S |
| CAS Number | 1186206-79-0 |
| Solubility (25°C) | DMSO: ≥ 30 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Ephrin Receptor Products |
|---|
| NVP-BHG712 isomer
NVP-BHG712 isomer, a regioisomer of NVP-BHG712, shows conserved non-bonded binding to EPHA2 and EPHB4. |
| ALW-II-49-7
ALW-II-49-7 is a selective EphB2 kinase inhibitor with an EC50 value of 40 nM in cell. |
| 123C4
123C4 is a potent, selective and competitive agonist of the receptor tyrosine kinase EPHA4, with a Ki value of 0.65 μM. |
| Urolithin D
Urolithin D is competitive and reversible antagonist of EphA receptors. |
| Eph inhibitor 1
Eph inhibitor 1 is a potent Eph inhibitor. |
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