Resistant to selumetinib

Selumetinib is an oral non-adenosine-5-triphosphate (ATP) competitive inhibitor that is highly specific for MEK1/2. It is a potent, tight-binding, non-competitive MEK inhibitor with a median inhibitory concentration (IC50) of 14.1 nmol L-1 against purified MEK1 and no inhibition of over 40 other serine/threonine kinases at 10 μMol/L-1.

In mouse xenograft studies, a dose of 10 mg/kg-1 per day achieved sustained inhibition of ERK activity in tumors. The safety and tolerability of selumetinib was evaluated in a two-part, multicenter, dose-escalation Phase I clinical study, which demonstrated the tolerability of selumetinib, with the most common associated toxicities being rash, diarrhea, nausea, and fatigue. In the current study, we have shown that treatment with 8-Cl-cAMP, a cAMP analog that specifically inhibits PKAI, is able to overcome resistance to MEK inhibition in selumetinib-resistant cancer cell lines in vitro and in vivo. These results demonstrate that the PKA pathway can be activated in human cancer cells that are intrinsically resistant to selective MEK inhibitors and represent a rationale for studies combining MEK and PKA inhibitors in cancer therapy.

SelumetinibThe original drug has been launched in China, but it has not yet entered the scope of medical insurance. SpecificationThe price of 10mg*60 tablets per box may be more than 20,000 yuan, which is relatively expensive. Selumetiniboriginal drug marketed overseas, specifications10mg*60 capsules per box may cost more than RMB 50,000 (the price may fluctuate due to exchange rates). The ingredients of the original selumetinib sold domestically and abroad are basically the same. There is currently no generic version of selumetinib produced and marketed. For more drug information and specific prices, please consult the medical consultant of Yaode.