Drug inhibitor against migration and invasion of cancer cells and methods of treating against metastasis of cancer cells

Inventors

Ullah, Hemayet • Dakshanamurthy, Sivanesan

Assignees

Howard University • Georgetown University

Abstract

A method for treating against, or at least inhibiting or suppressing, the proliferation of a cancer involves administering a compound, a tautomer, or a pharmaceutically acceptable salt thereof, in an amount effective for inhibiting metastasis of cancer cells, wherein the compound is represented by the formula (1):wherein each R1 independent of the other and represents a halogen atom selected from the group consisting of bromo, chloro, fluoro and iodo.

Core Innovation

The patent describes RACK1 (Receptor of Activated Protein Kinase C 1) functional inhibitors for inhibiting metastasis in cancers. It centers on administering a compound, a tautomer of the compound, or a pharmaceutically acceptable salt of the compound or of the tautomer in an amount effective for inhibiting metastasis. The compounds are represented by a specific formula having a tricyclic/azole-thiol scaffold in which each R1 is a halogen atom selected from bromine, chlorine, fluorine and iodine.

The patent states that the cancer is breast cancer or glioblastoma in which RACK1 functions as a positive regulator for cancer cell migration and metastasis. Functional inactivation of RACK1 in such cancers is proposed to impair key tyrosine phosphorylation events associated with RACK1, including human Y246 and plant Y248, and thereby disrupt RACK1-associated signaling complexes. These complexes are described as involving Src, FAK, integrins, and EMT markers, including N-cadherin.

The disclosed functional inactivation is also described to affect actin-based structures and vimentin-related processes associated with metastasis. The patent describes impacts on filopodia, lamellipodia, and stress fibers, and on vimentin-related processes. It further describes changes in RACK1-associated localization and extracellular matrix-related factors, including LamB1, and altered phosphorylation of FAK at Y397. Example compounds include SD-29-14 as a dichloro derivative, and comparative efficacy is discussed.

Claims Coverage

The partial content provides two independent claims. Each independent claim focuses on administering a defined RACK1-targeting compound family, including tautomers and pharmaceutically acceptable salts, characterized by a halogen-substituted formula, for treating breast cancer or glioblastoma where RACK1 is a positive regulator of migration and metastasis.

Across the independent claims, the main inventive elements are administration of a compound, tautomer, or pharmaceutically acceptable salt from a defined R1 halogen-substituted formula, and selection of breast cancer or glioblastoma where RACK1 is a positive regulator of cancer cell migration and metastasis to inhibit metastasis.

Stated Advantages

Documented Applications