TMTC2 Inhibitors

Chemical inhibitors of TMTC2 can employ various strategies to reduce the activity of this protein by influencing the intracellular calcium levels and calcium signaling pathways upon which TMTC2 function depends. Calcium chloride, for example, increases intracellular calcium concentrations, which can lead to the inhibition of TMTC2 when excessive calcium triggers a shutdown of its activity. Similarly, BAPTA acts as a calcium chelator to lower intracellular calcium levels, thus potentially inhibiting TMTC2 if its function requires calcium binding or is regulated by calcium concentrations. Ruthenium Red and 2-Aminoethoxydiphenyl borate (2-APB) target calcium channels and IP3 receptors, respectively, to control calcium influx and release from internal stores, which may inhibit TMTC2 if it is part of a calcium-dependent signaling cascade.

In addition to direct calcium modulation, several chemicals target secondary messengers and enzymes that are critical for calcium-mediated signaling pathways. Bisindolylmaleimide I and U73122 suppress the activity of protein kinase C (PKC) and phospholipase C, respectively, which are both important for the activation of proteins downstream of calcium signaling. If TMTC2's activity is contingent upon PKC-mediated phosphorylation, inhibition of this enzyme will decrease TMTC2 function. Thapsigargin and Cyclopiazonic acid inhibit the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA), leading to ER calcium store depletion, which may inhibit TMTC2 by disrupting its calcium homeostasis. ML-7, by inhibiting myosin light chain kinase (MLCK), could downregulate TMTC2 if its activity is intertwined with cytoskeletal dynamics controlled by MLCK. W-7, a calmodulin inhibitor, can also inhibit TMTC2 by blocking calmodulin-dependent regulatory mechanisms. Lastly, SKF-96365 and Xestospongin C, which inhibit receptor-mediated calcium entry channels and the IP3 receptor, respectively, further demonstrate the potential to inhibit TMTC2 by hampering essential components of the calcium signaling mechanisms that might regulate its function.