| abstract |
The present invention provides a protein degradation targeting BCR-ABL compound represented by formula (I) and an antitumor application thereof. The compound represented by formula (I) has the effects of degrading and inhibiting BCR-ABL target proteins, and mainly consists of four parts; the first part, BCR-ABL-TKIs, is a compound having BCR-ABL tyrosine kinase inhibitory activity; the second part, LIN, is a link unit; the third part, ULM, is a small molecular ligand of VHL or CRBN proteases having a ubiquitination function; and the fourth part, group A, is a carbonyl group, which covalently binds BCR-ABL-TKIs and LIN, and covalently binds LIN and ULM. A series of compounds designed and synthesized in the present invention have extensive pharmacological activities, have the functions of degrading BCR-ABL proteins and inhibiting BCR-ABL activity, and can thus be used in related tumor treatment. |