T-type calcium channel inhibitors for treatment of cancer

Abstract

Presented herein are compounds that inhibit T-type Ca2+ channel activity in a cell when the cell membrane potential is about -90 mV. Preferred compounds inhibit T-type Ca2+ channel activity with an IC50 of 10 [mu]M or less at a membrane potential of about -90 mV. Preferred compounds show selectivity for inhibiting T-type Ca2+ channel activity at about -90 mV, relative to inhibition of T-type Ca2+ channel activity at about -30 mV to -60 mV, of 10: 1 or less. Also provided are methods for identifying compounds that inhibit T-type Ca2+ channel activity in a cell when the cell membrane potential is about -90 mV, and compounds identified by such methods.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application No. 61 / 751,038, filed January 10, 2013, the entire disclosure of which is incorporated herein by reference. technical field [0003] The present disclosure relates to therapeutically useful compounds, methods of treatment and methods of identifying therapeutically useful compounds. Background technique [0004] Ca at different points in the cell cycle 2+ Influx is critical for progression, although Ca 2+ The precise roles and pathways through which it functions remain largely elusive. More recently, it has been possible to integrate a pathway 1，2 , that is, Ca 2+ Role of influx in achieving crossing of the G1 / S transition or checkpoint, a growth factor-driven unidirectional step in cell cycle progression. The G1 / S transition functions to integrate information from many fundamental cellular inputs, including growth factor signaling and nutrient avai...

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Problems solved by technology

There is also evidence depicting Ca 2+ Regulation of input in electrically non-excitable cells, but this is unlikely to account for the Ca requirement for cell division 2+ input and across the G1 / S boundary

Then, expression of T-type Ca in cancer cells and stem cells 2+ channel, but it is a voltage-gated

Because most types of cancer cells and stem cells do not possess the action potentials thought to be necessary to regulate such voltage-gated channels, little is known about the function or regulation of these channels

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