3 results about "Drug resistant mutants" patented technology

The present invention provides arylphosphine oxides with kinase inhibitory activity, which can effectively inhibit the activities of various types of EGFR resistant mutants (such as EGFR del19 , EGFR del19 / T790M , EGFR del19 / C797S , EGFR T790M / L858R , EGFR L858R / C797S , EGFR del19 / T790M / C797S , EGFR L858R / T790M / C797S ), and also has a significant inhibitory effect on the ALK fusion gene and mutants (such as L1196M), and can be used for the treatment, combination therapy or prevention of various cancers.

Provided are a cyclic 2-aminopyrimidine compound having a structure as shown in formula (I), or a pharmaceutically acceptable salt, stereoisomer or prodrug molecule thereof, and a use thereof. The compound can effectively inhibit the activity of EGFR protein kinase drug-resistant mutants (such as EGFRT790M and EGFR19del / T790M / C797S), and can overcome the clinical drug resistance of patients suffering from tumors such as non-small cell lung cancer induced by existing third-generation selective EGFRT790M small molecule inhibitors Osimertinib (AZD9291), Olmutinib (HM6171), Rociletinib (CO-1686) and the like.

The invention belongs to the field of medicine, and provides a PROTAC compound targeting PI3Kalpha and preparation and application thereof. The PROTAC compound is selected from a compound as shown in a formula (I) or pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof. The compound realizes specific degradation of PI3Kalpha protein instead of pure enzyme activity inhibition by combining an allosteric site of PI3Kalpha and E3 ligase at the same time. The compound still keeps efficient degradation activity on clinically common drug-resistant mutants, and the problem that a traditional small-molecule inhibitor is prone to drug resistance is effectively solved. The structure of the formula (I) is shown in the specification.