ArticleBritish journal of pharmacology2015
Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 120 citations in OpenAlex.
- Urotensin II Receptor Deletion Mitigates Kidney Injury and Renal Lipid Remodeling in Mice Fed a Long-Term High-Fat Diet.FASEB bioAdvances · 2026Article
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- The photoswitchable cannabinoid azo-HU308 enables optical control of CaFEBS open bio · 2026Article
- TRPC Channels as Mediators of Hypoxia-Induced Pulmonary Hypertension in Obstructive Sleep Apnea.International journal of molecular sciences · 2026Review
- TRPC6 Inhibition Attenuates Renal Tubulointerstitial Fibrosis via the Reactive Oxygen Species/TXNIP/NLRP3 Signaling Pathway.Kidney & blood pressure research · 2026Article
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- TRPC6 effects on albumin permeation, nephrin shedding, and apoptosis in podocytes: Role of calcineurin and metalloproteases.Physiological reports · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Non-Ser36 phosphorylated p66Shc inhibits TRPC-dependent and TRPC-independent calcium influx in vascular smooth muscle cells.Biochemical and biophysical research communications · 2025Article
- GsMTx-4 inhibits the exercise pressor reflex and the muscle mechanoreflex primarily through TRPC inhibition.The Journal of physiology · 2025Article
- Calcium Oscillations Within Juxtaglomerular Cell Clusters Control Renin Release.Circulation research · 2025Article
- Inhibition and potentiation of the exercise pressor reflex by pharmacological modulation of TRPC6 in male rats.The Journal of physiology · 2025Article
- Engineered 3D Kidney Glomerular Microtissues to Model Podocyte-Centric Diseases for the Validation of New Drug Targets.Advanced healthcare materials · 2025Article
- Inhibition of Renin Release, a Crucial Event in Homeostasis, is Mediated by Coordinated Calcium Oscillations within Juxtaglomerular Cell Clusters.bioRxiv : the preprint server for biology · 2025Article
- Unlocking the potential of cardiac TRP channels using knockout mice models.Frontiers in physiology · 2025Article
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- Article
- Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.Medicinal research reviews · 2024Review
- Non-voltage-gated CaAmerican journal of physiology. Renal physiology · 2024Review
- Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats.Respiratory research · 2024Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe cation channel transient receptor potential canonical (TRPC) 6 has been associated with several pathologies including focal segmental glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate the therapeutic potential of these agents. EXPERIMENTAL APPROACH: A library of potential TRPC channel inhibitors was designed and synthesized. Activity of the compounds was assessed by measuring intracellular Ca(2+) levels. The lead compound SAR7334 was further characterized by whole-cell patch-clamp techniques. The effects of SAR7334 on acute hypoxic pulmonary vasoconstriction (HPV) and systemic BP were investigated. KEY
resultsSAR7334 inhibited TRPC6, TRPC3 and TRPC7-mediated Ca(2+) influx into cells with IC50 s of 9.5, 282 and 226 nM, whereas TRPC4 and TRPC5-mediated Ca(2+) entry was not affected. Patch-clamp experiments confirmed that the compound blocked TRPC6 currents with an IC50 of 7.9 nM. Furthermore, SAR7334 suppressed TRPC6-dependent acute HPV in isolated perfused lungs from mice. Pharmacokinetic studies of SAR7334 demonstrated that the compound was suitable for chronic oral administration. In an initial short-term study, SAR7334 did not change mean arterial pressure in spontaneously hypertensive rats (SHR). CONCLUSIONS AND IMPLICATIONS: Our results confirm the role of TRPC6 channels in hypoxic pulmonary vasoregulation and indicate that these channels are unlikely to play a major role in BP regulation in SHR. SAR7334 is a novel, highly potent and bioavailable inhibitor of TRPC6 channels that opens new opportunities for the investigation of TRPC channel function in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.