TRPC6 (Transient Receptor Potential Cation Channel Subfamily C Member 6)

P3, N=105, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

P3, N=286, Recruiting, Boehringer Ingelheim | N=103 --> 286

P3, N=103, Recruiting, Boehringer Ingelheim | N=76 --> 103

P3, N=61, Recruiting, Boehringer Ingelheim | N=38 --> 61

P2/3, N=38, Not yet recruiting, Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A.

BI-749327 directly binds TRPC6, inhibiting its channel activity and expression, thereby reducing [Ca2+]i and downstream Ca2+-related PI3K/AKT/mTOR signaling to suppress HCC progression. This study elucidates the BI-749327-TRPC6 interaction, provides a molecular basis for developing novel anti-HCC drugs, and establishes a research paradigm for other TRPC6 inhibitors.

P3, N=286, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

The TRPC6 A404V is a gain-of-function variant that exhibits enhanced activity in the presence of doxorubicin. Therefore, the TRPC6 A404V variant represents a risk factor for anthracycline-induced cardiotoxicity in patients with cancer.

Gain-of-function mutations in the transient receptor potential 6 (TRPC6) channel have recently been recognized as risk factors for both doxorubicin (DOX)-induced cardiomyopathy...Importantly, the results obtained from molecular docking and patch clamp recordings were strongly correlated, showing an 82% concordance, higher than the predictions from AlphaMissense. These findings indicate that our computational analysis provides a rapid and reliable method for predicting the functional impact of TRPC6 missense variants, which may aid clinical decision-making in cancer patients receiving chemotherapy.

In this study, a CIPN mouse model with emotional disorders was established through the intervention of cisplatin for 21 d, which was validated by the von Frey test, adhesive removal test, open-field test and elevated plus-maze test...Mechanically, EA treatment significantly inhibited TRPC6 activation, reducing the Ca2+ influx and attenuating p-PKC level, thereby decreasing the release of excitatory neurotransmitter glutamate in the PVT. Our findings revealed a novel mechanism through which calcium influx-mediated glutamatergic neuron activation in PVT participated in the CIPN and provided evidence that TRPC6/PKC may be potent targets for the EA effect.

Importantly, treatment of TNBC cells with a TRPC6 inhibitor reduces metastasis significantly, an effect that is mitigated by a ferroptosis inhibitor. These results indicate that a sub-population of TNBC cells characterized by TRPC6 expression has the potential to form metastases by evading ferroptosis.

In contrast to published researches, we found that TRPC6 expression was negatively correlated with breast cancer cell proliferation and metastasis abilities, suggesting TRPC6 as a promising prognostic biomarker for breast cancer, where low expression of TRPC6 was related to worse prognoses. This research raises the necessity of rethinking the mechanism perspective and targetability of TRPC6 in breast cancer, which warrants further investigation.