Study on Small Molecular Lead Compounds with Selectively Inhibitory Effect on Tumor Cell-Induced Platelet Aggregation

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

The cancer cell metastasis including angiogenesis, migration, invasion, move to the lymph and blood vessels, and translocation to anatomically distant organs, where after extravasation they colonize the tissue to develop secondary metastases. Tumor cells can stimulate platelet activation and form the aggregation complex with platelets in the vascular circulation system. This interaction is termed as tumor cell-induced platelet aggregation (TCIPA). The ability of tumor cells to induce platelet aggregation has been proven to highly correlate with the metastatic capability of malignant tumor. Therefore, inhibiting TCIPA is able to use as the strategies for treatment of tumor metastasis. Podoplanin (PDPN) is a membrane protein found in many tumor cells, and correlates with their capacity to induce platelet aggregation and to metastasise. Furthermore, PDPN also is a ligand of platelet C-type lectin receptor (CLEC-2), and mediates activation of platelet. These indicate inhibiting the interaction between CLEC-2 and PDPN is a therapy target for treatment of tumor metastasis. A previous study enabled us to identify three components (LFH-7, LFH-20, and NB-1), which selectively inhibited PDPN-induced platelet aggregation. Of these, NB-1 is a first small molecular agent directly blocking interaction between CLEC-2 and PDPN. In addition, NB-1 is patent pending now. Therefore, the NB-1 and LFHs derivatives will be designed, synthesized, evaluated, and developed using structural-based design. Finally, the pharmacokinetic analysis of bioactive derivatives will also be determined herein.

Project IDs

Project ID:PC10401-0166
External Project ID:NSC102-2320-B182-008-MY3
StatusFinished
Effective start/end date01/08/1531/07/16

Keywords

  • Tumor cell -induced platelet aggregation
  • Podoplanin
  • Metastasis
  • Platelet C-type

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