Protein tyrosine kinases (PTKs) play a pivotal role in the signal transduction pathways, and their deregulation is highly related with the oncology including bladder, breast, colon, and lung cancers. Com-pounds that inhibit the kinase activity of PTKs are potential chemotherapeutics to treat tumors. With the emergence of the multiple drug resistance of tumor cells against the existing PTK inhibitors, new mechanism PTK inhibitors are designed and developed. This review is focused on the recent advance of the discovery and development of the small molecular PTK inhibitors, categorized according to the mode of ac-tion. Furthermore, the synthesis of the typical structures is described.

Key words: tyrosine kinases, inhibitors, cancer, DFG motif, molecular targeted therapy