The Synthesis and Effects of a Novel TRPC6 inhibitor, BP3112, on Hepatocellular Carcinoma

References

• Sung H , FerlayJ, SiegelRLet al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.71(3), 209–249 (2021).
   PubMed Web of Science ®Google Scholar
• Nault JC , VillanuevaA. Intratumor molecular and phenotypic diversity in hepatocellular carcinoma. Clin. Cancer Res.21(8), 1786–1788 (2015).
   PubMed Web of Science ®Google Scholar
• Llovet JM , MontalR, SiaD, FinnRS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat. Rev. Clin. Oncol.15(10), 599–616 (2018).
   PubMed Web of Science ®Google Scholar
• Jardin I , Diez-BelloR, FalconDet al. Melatonin downregulates TRPC6, impairing store-operated calcium entry in triple-negative breast cancer cells. J. Biol. Chem.296, 100254 (2021).
   PubMed Web of Science ®Google Scholar
• Roderick HL , CookSJ. Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nat. Rev. Cancer8(5), 361–375 (2008).
   PubMed Web of Science ®Google Scholar
• Monteith GR , PrevarskayaN, Roberts-ThomsonSJ. The calcium-cancer signalling nexus. Nat. Rev. Cancer17(6), 367–380 (2017).
   PubMed Web of Science ®Google Scholar
• Karpurapu M , WangD, Van QuyenDet al. Cyclin D1 is a bona fide target gene of NFATc1 and is sufficient in the mediation of injury-induced vascular wall remodeling. J. Biol. Chem.285(5), 3510–3523 (2010).
   PubMed Web of Science ®Google Scholar
• Chigurupati S , VenkataramanR, BarreraDet al. Receptor Channel TRPC6 Is a Key Mediator of Notch-Driven Glioblastoma Growth and Invasiveness. Cancer Res.70(1), 418–427 (2010).
   PubMed Web of Science ®Google Scholar
• Bouron A , ChauvetS, DryerS, RosadoJA. Second messenger-operated calcium entry through TRPC6. Adv. Exp. Med. Biol.898, 201–49 (2016).
   PubMed Web of Science ®Google Scholar
• Kuwahara K , WangY, McAnallyJet al. TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J. Clin. Invest.116(12), 3114–3126 (2006).
   PubMed Web of Science ®Google Scholar
• Zhou L , XieX. RNA-binding protein CELF2 inhibits breast cancer cell invasion and angiogenesis by downregulating NFATc1. Exp. Ther. Med.22(2), 898 (2021).
   PubMed Web of Science ®Google Scholar
• Wang SH , KangXM, CaoSQet al. Calcineurin/NFATc1 pathway contributes to cell proliferation in hepatocellular carcinoma. Digest Dis. Sci.57(12), 3184–3188 (2012).
   PubMed Web of Science ®Google Scholar
• Xu SR , ShuPH, ZouSet al. NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL-mediated extrinsic signaling pathway. Cancer MED-US7(9), 4701–4717 (2018).
   PubMed Web of Science ®Google Scholar
• Bao SX , JiangXP, JinSet al. TGF-beta 1 induces immune escape by enhancing PD-1 and CTLA-4 expression on t lymphocytes in hepatocellular carcinoma. Front. Oncol.11, 694145 (2021).
   PubMed Web of Science ®Google Scholar
• Ding X , HeZ, ZhouKet al. Essential role of TRPC6 channels in G2/M phase transition and development of human glioma. J. Natl. Cancer Inst.102(14), 1052–1068 (2010).
   PubMedGoogle Scholar
• Song J , WangY, LiXet al. Critical role of TRPC6 channels in the development of human renal cell carcinoma. Mol. Biol. Rep.40(8), 5115–5122 (2013).
   PubMed Web of Science ®Google Scholar
• Sanij E , HannanKM, XuanJCet al. CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer. Nat. Commun.11(1), 2641 (2020).
   PubMed Web of Science ®Google Scholar
• Chen XJ , SoochG, DemareeISet al. Transient receptor potential canonical (TRPC) channels: then and now. Cells BASEL9(9), 1983 (2020).
   PubMed Web of Science ®Google Scholar
• Merritt JE , ArmstrongWP, BenhamCDet al. SK&F 96365, a novel inhibitor of receptor-mediated calcium entry. Biochem J.271(2), 515–522 (1990).
   PubMed Web of Science ®Google Scholar
• Lin BL , MateraD, DoernerJFet al. In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease. Proc. Natl. Acad. Sci. USA.116(20), 10156–10161 (2019).
   PubMed Web of Science ®Google Scholar
• Maier T , FollmannM, HesslerGet al. Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels. Brit. J. Pharmacol.172(14), 3650–3660 (2015).
   PubMed Web of Science ®Google Scholar
• Urban N , WangL, KwiekSet al. Identification and validation of larixyl acetate as a potent TRPC6 inhibitor. Mol. Pharmacol.89(1), 197–213 (2016).
   PubMed Web of Science ®Google Scholar
• Chehardoli G , BahmaniA. Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review. Mol. Divers.25(1), 535–550 (2021).
   PubMed Web of Science ®Google Scholar
• Gasteiger J , MarsiliM. Iterative partial equalization of orbital electronegativity – a rapid access to atomic charges. Tetrahedron36(22), 3219–3228 (1980).
   Web of Science ®Google Scholar
• Tang QL , GuoWJ, ZhengLet al. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Cell Res.28(7), 746–755 (2018).
   PubMed Web of Science ®Google Scholar
• White AW , CarpenterN, LottinJet al. Synthesis and evaluation of novel anti-proliferative pyrroloazepinone and indoloazepinone oximes derived from the marine natural product hymenialdisine. Eur. J. Med. Chem.56, 246–253 (2012).
   PubMed Web of Science ®Google Scholar
• Horinouchi T , TeradaK, HigaTet al. Function and regulation of endothelin type A receptor-operated transient receptor potential canonical channels. J. Pharmacol. Sci117(4), 295–306 (2011).
   PubMed Web of Science ®Google Scholar
• Guo W , TangQ, WeiMet al. Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites. Neuron110(6), 1023 (2022).
   PubMed Web of Science ®Google Scholar
• Ahmad AA , StreiffME, HunterC, SachseFB. Modulation of calcium transients in cardiomyocytes by transient receptor potential canonical 6 channels. Front. Physiol.11, 44 (2020).
   PubMed Web of Science ®Google Scholar
• Su Y , ChenQ, JuYet al. Palmitate induces human glomerular mesangial cells fibrosis through CD36-mediated transient receptor potential canonical channel 6/nuclear factor of activated T cell 2 activation. Biochim. Biophys. Acta Mol. Cell Biol. Lipids1865(12), 158793 (2020).
   PubMed Web of Science ®Google Scholar
• Qie S , DiehlJA. Cyclin D1, cancer progression, and opportunities in cancer treatment. J. Mol. Med.94(12), 1313–1326 (2016).
   PubMed Web of Science ®Google Scholar
• Qi HQ , LuYY, LvJet al. The long noncoding RNA lncPARP1 contributes to progression of hepatocellular carcinoma through up-regulation of PARP1. Biosci. Rep.38(3), BSR20180703 (2018).
   PubMedGoogle Scholar
• El Boustany C , BidauxG, EnfissiAet al. Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation. Hepatology47(6), 2068–2077 (2008).
   PubMed Web of Science ®Google Scholar
• Wen L , LiangC, ChenEJet al. Regulation of multi-drug resistance in hepatocellular carcinoma cells is TRPC6/calcium dependent. Sci. Rep.6, 23269 (2016).
   PubMed Web of Science ®Google Scholar
• Nakuluri K , NishadR, MukhiDet al. Cerebral ischemia induces TRPC6 via HIF1 alpha/ZEB2 axis in the glomerular podocytes and contributes to proteinuria. Sci. Rep.9, 17897 (2019).
   PubMed Web of Science ®Google Scholar
• Marchi S , GiorgiC, GalluzziL, PintonP. Ca2+ fluxes and cancer. Mol. Cell.78(6), 1055–1069 (2020).
   PubMed Web of Science ®Google Scholar
• Ding M , WangH, QuCet al. Pyrazolo[1,5-a]pyrimidine TRPC6 antagonists for the treatment of gastric cancer. Cancer Lett.432, 47–55 (2018).
   PubMed Web of Science ®Google Scholar
• Iyer SC , KannanA, GopalAet al. Receptor channel TRPC6 orchestrate the activation of human hepatic stellate cell under hypoxia condition. Exp. Cell. Res.336(1), 66–75 (2015).
   PubMed Web of Science ®Google Scholar
• Makarewich CA , ZhangHY, DavisJet al. Transient receptor potential channels contribute to pathological structural and functional remodeling after myocardial infarction. Circ. Res.115(6), 567 (2014).
   PubMed Web of Science ®Google Scholar
• Soni H , AdebiyiA. TRPC6 channel activation promotes neonatal glomerular mesangial cell apoptosis via calcineurin/NFAT and FasL/Fas signaling pathways. Sci. Rep.6, 29041 (2016).
   PubMed Web of Science ®Google Scholar
• Im SH , RaoA. Activation and deactivation of gene expression by Ca2+/calcineurin-NFAT-mediated signaling. Mol. Cells18(1), 1–9 (2004).
   PubMed Web of Science ®Google Scholar
• Mueller MR , RaoA. NFAT, immunity and cancer: a transcription factor comes of age. Nat. Rev. Immunol.10(9), 645–656 (2010).
   PubMed Web of Science ®Google Scholar
• Carvalho A , GouveiaL, KannaCRet al. Understanding the structural and dynamic consequences of DNA epigenetic modifications: computational insights into cytosine methylation and hydroxymethylation. Epigenetics9(12), 1604–1612 (2014).
   PubMed Web of Science ®Google Scholar
• Souza W , PiperniSG, LaviolaPet al. The two faces of titanium dioxide nanoparticles bio-camouflage in 3D bone spheroids. Sci. Rep.9(1), 9309 (2019).
   PubMedGoogle Scholar
• Glassford J , SoeiroI, SkarellSMet al. BCR targets cyclin D2 via Btk and the p85 alpha subunit of PI3-K to induce cell cycle progression in primary mouse B cells. Oncogene22(15), 2248–2259 (2003).
   PubMed Web of Science ®Google Scholar
• Patra AK , AvoisA, ZahediRPet al. An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development. Nat. Immunol.14(2), 127–135 (2013).
   PubMed Web of Science ®Google Scholar
• Heit JJ , ApelqvistAA, GuXYet al. Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function. Nature443(7109), 345–349 (2006).
   PubMed Web of Science ®Google Scholar
• Kawamura T , OnoK, MorimotoTet al. Endothelin-1-dependent nuclear factor of activated T lymphocyte signaling associates with transcriptional coactivator p300 in the activation of the B cell leukemia-2 promoter in cardiac myocytes. Circ. Res.94(11), 1492–1499 (2004).
   PubMed Web of Science ®Google Scholar