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  • A calcium (Ca2+) release-activated channel (CRAC) inhibitor, with potential anti-inflammatory and protective activities. Upon administration, CM4620 targets, binds to and inhibits the calcium release-activated calcium channel protein 1 (Orai1), which forms the pore of CRAC, and is expressed on both parenchymal cells and immune cells. This prevents the transport of extracellular Ca2+ into the cell and inhibits the subsequent activation of Ca2+-mediated signaling and transcription of target genes. This may prevent Ca2+ entry-mediated cell death. It may also inhibit the proliferation of immune cells and prevents the release of various inflammatory cytokines in immune cells, such as interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-a). This may lead to a reduction of inflammatory responses in inflammatory-mediated diseases. CRACs, specialized plasma membrane Ca2+ ion channels composed of the plasma membrane based Orai channels and the endoplasmic reticulum (ER) stromal interaction molecules (STIMs), mediate store operated Ca2+ entry (SOCE) and play a key role in calcium homeostasis. CRACs are overactivated in a variety of cell types, especially certain immune cells during inflammation, including T-lymphocytes, neutrophils and macrophages.
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