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Searching for the seed round of GPCR Unicorn

2023/09/06

GPCR is a promising drug target

GPCRs, or G protein-coupled receptors, are the largest family of membrane proteins in the mammalian genome. There are more than 800 members of the GPCR protein family in the human genome, which are widely distributed in the central nervous system, immune system, cardiovascular, retinal and other tissues and organs, and participate in the regulation of many different biological functions. As a transmembrane protein, GPCR has seven transmembrane (7TM) domains, so it is also called seven transmembrane receptors (7TMR). And the C terminus of its peptide chain and the intracellular loop connecting the 5th and 6th transmembrane helix have G protein (guanylate-binding protein) binding sites. GPCRs, after being stimulated by extracellular signaling molecules, mediate signaling through binding to intracellular G proteins, and play a key role in physiological activities such as cell proliferation, growth and migration.

GPCRs are widely distributed and complex, related to the occurrence and progression of a variety of diseases, and are highly potential drug targets.

GPCR regulates diseases including oncology, metabolic diseases, inflammation, fibrosis, pain, nephropathy, etc., and in recent years, it has been shown to be involved in the research of respiratory diseases, ophthalmology, cardiovascular diseases and infectious diseases. In the existing research, about 270 GPCR targets have a strong theoretical basis for disease and have the potential to develop antibody-targeted drugs. According to statistics, drugs targeting GPCRs account for more than 30% of all approved drugs.

Honor of Horst Vogel

Professor Horst Vogel, a Swiss national, is the founding scientist of Shenzhen Alpha Molecular Technology Co., Ltd., a seed round project invested by New Value Capital, and the chief scientist (full-time) of the Computer Aided Drug Design Research Center of Shenzhen Advanced Institute of Medicine. He was elected a member of the Swiss Academy of Sciences in 2004, a member of the American Academy of Inventions in 2014, and an honorary professor of lifetime achievement at the Swiss Federal Institute of Technology (EPFL, 14th in the world) in the same year.

Academician Horst Vogel is mainly engaged in biological frontier technological innovation represented by the study of membrane protein structure and function, and is committed to the research and development of innovative drugs. As one of the most important drug targets, about 60% of drugs currently act on membrane proteins. In view of the difficulties and key bottlenecks in the development of membrane protein drugs, Academician Vogel invented a series of world-first biochip technologies, which systematically solved the core problems in drug development, and a number of cutting-edge patented technologies were licensed to international large pharmaceutical companies.

Professor Horst Vogel has made some of his academic achievements in the field of GPCR

Horst Vogel - Publications (1976 – June 2021)

(Google Scholar >20000 citations; h=76)

Due to space limitations, more than 1976 papers by Professor Vogel from 2005 to 100 are not listed here, please request them

149. C Danelon C Sanchi, J Brugger and H Vogel: Fabrication and functionalization of nanochannels by electron-beam-induced silicon dioxide deposition.

Langmuir 22, 10711-10715 (2006).

150. C Danelon, MG Jenke, C. Schreiter, GM Kim, JB Perez, C Santschi, J Brugger and H Vogel: Micro- and nanostructured devices for the investigation of biomolecular interactions. Chimia 60, A754-A760 (2006).

151. C Danelon, J Grandl, R Hovius and H Vogel: Modulation of proton-induced current fluctuations in human nicotinic acetylcholine receptor channel.

Biochim. Biophys. Acta 1768, 76-89 (2007).

152. MG Jenke, C Schreiter, GM Kim. H Vogel and J Brugger: Micropositioning and microscopic observation of individual picoliter-sized containers within SU-8 microchannels. Microfluid. Nanofluid. 3, 189-194 (2007).

153. J Grandl, E Sakr, F Kotzyba-Hibert, S Bertrand, D Bertrand, H Vogel, M Goeldner and R Hovius: Fluorescent epibatidine agonists for neuronal and muscle-type nicotinic acetylcholine receptors. Angew. Chem. Int. Ed. 46, 3505-3508 (2007).

154. EG Guignet, J-M Segura, R Hovius and H Vogel: Repetetive reversible labeling of proteins at polyhistidine sequences improves substantially single-molecule imaging in live cells: Agonist-induced mobility modulation of ionotropic serotonin receptors. ChemPhysChem 8, 1221-1227 (2007).

155. EC Riera, H Vogel, SA Simon and J LeCoutre: Artificial Sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors.

Am. J. Physiol. Regulatory Integrative Comp. Physiol. 293, 626-634 (2007).

156. D Abankwa and H Vogel: FRET reveals subclass and activation state specific lateral segregation of heterotrimeric G proteins in living cells.

J. Cell Sci. 120, 2953-2962 (2007).

157. H Pick, H Jankevics and H Vogel: Distribution plasticity of the human estrogen receptor a in live cells: Distinct imaging of consecutively expressed receptors. J. Mol. Biol. 374, 1213-1223 (2007).

158. M Prummer and H Vogel: Signaling and mobility of single receptor proteins in live cells. In: Single Molecules and Nanotechnology.Springer Series in Biophysics, Vol. 12 (2007).

159. F. Merenda, J. Rohner, P. Pascoal, J. M. Fournier, H. Vogel, R. P. Salathé: Refractive multiple optical tweezers for parallel biochemical analysis in micro-fluidics. Proc. SPIE 6483, 64830A1-9 (2007).

160. P-Y Bolinger, D Stamou and H Vogel: An integrated self-assembled nanofluidic system for controlled biological chemistries. Angew. Chem. Int. Ed. 47, 5544-5549 (2008).

161. J-M Segura, P Guillaume, S Mark, D Dojcinovic, A Johannsen, G Bosshard, G Angelov, DF Legler, H Vogel, and IF Luescher: Increased mobility of major histocompatibility complex+-peptide complexes decreases the sensitivity of antigen recognition. J. Biol. Chem. 283, 2454-2463 (2008)

162. CE Riera, H Vogel, SA Simon, S Damak and J LeCoutre: The capsaicin receptor participates in artificial sweetener aversion. Biochem. Biophys. Res. Comm. 376, 653-657 (2008).

163. C Danelon, S Terrettaz, O Guenant, M Kudelka and H Vogel: Probing the function of ionotropic and G protein-coupled receptors in surface-confined membranes. Methods (invited review) 46, 104-115 (2008).

164. Y. Temiz, F. Gurkaynak, S. Terrettaz, H. Vogel, G. De Micheli, Y. Leblebici, C. Guiducci, and L. Benini: Real-Time High-Sensitivity Impedance Measurement Interface for Tethered BLM Biosensor Arrays. IEEE Sensors 2008, 650-653 (2008).

165. CE Riera, CMenozzi-Smarrito, M Affolter, S Michlig, C Munari, F Robert, H Vogel, SA Simon and J LeCoutre: Covalent and non-covalent ligand interactions in TRPA1 and TRPV1 channels with spicy molecules from Sichuan and Melegueta peppers. J. Neurosci. 29, 2654-2662 (2009).

166. BL Cook, D Steuerwald, L Kaiser, J Graveland-Bikker, M Vanberghem, AP Berke, K Herlihy, H Pick, H Vogel and S Zhang: Large-Scale Production and Study of a Synthetic GPCR: Human Olfactory Receptor 17-4. Proc. Natl. Acad. Sci. USA. 106, 11925-11930 (2009).

167. S Terrettaz, S Follonier, S Makoholiso and H Vogel: A synthetic membrane protein in tethered lipid bilayers for immunosensing in whole blood.

J. Struct. Biol. 168, 177-182 (2009).

168. S Etter, H Pick, L Bordoli, R Schmauder, T Schwede and H Vogel: Dual activities of odorant compounds on olfactory and nuclear hormone receptors. J. Biol. Chem. 284, 30547-30555 (2009).

169. O Zava, SM Zakeeruddin, C Danelon, H Vogel, M Grätzel, PJ Dyson: A cytotoxic Ruthetium tris(bipyridyl) complex that accumulates at plasma membranes.

ChemBioChem 10, 1796-1800 (2009).

170. P Pascoal, D Kosanic, M Gjoni and H Vogel: Membrane nanotubes drawn by optical tweezers transmit electrical signals between mammalian cells over longdistances. LabOnChip 10, 2235-2241 (2010).

171. J Piguet, C Schreiter, JM Segura, H Vogel, R Hovius: Acetylcholine receptor organization in membrane domains in muscle cells.

J. Biol. Chem. 286, 363-369 (2011).

172. AW Schmid, E Condemi, G Tuchscherer, D Chappe, M Mutter, H Vogel, M Moniatte, YO Tsybin: Tissue transglutaminase-mediated glutamine deaidation of beta-amyloid peptide increases peptide solubility, whereas enzymatic cross-linking and peptide fragmentation may serve as molecular triggers for rapid peptide aggregation.J. Biol. Chem. 286, 12172-12188 (2011).

173. L Fornelli, AW Schmid, L Grasso, H Vogel, YO Tsybin: Deamidation and transamidation of substance P by tissue transglutaminase revealed by electron-capture dissociation Fourier transform mass spectrometry.

Chemistry Eur. J. 17, 486-497 (2011).

174. O Baud, S Etter, M Spreafico, L Bordoli, T Schwede, H Vogel, H Pick: Mouse eugenol odorant receptor: Structural and functional plasticity of a broadly tuned odorant binding pocket.Biochemistry 50, 843-853 (2011).

175. RM Bill, PJF Henderson, S Iwata, ERS Kunji, H Michel, R Neutze, S Newstead, B Pooman, CG Tate, H Vogel: Overcoming barriers to membrane protein structure determination.Nature Biotechnol. 29, 335-340 (2011).

176. M Werner, F Merenda, J Piguet, RP Salathe, H Vogel: Microfluidic array cytometer based on refractive optical tweezers for parallel trapping, imaging and sorting of individual cells. Lab Chip, 11, 2432-2439 (2011).

177. R Schmauder, D Kosanic, R Hovius, H Vogel: Correlated optical and electrical single-molecule measurements reveal conformational diffusion from ligand binding to channel gating in the nicotinic acetylcholine receptor.

ChemBioChem 12, 2431-2434 (2011).

178. D Thamani, H Vogel, H Pick: High yield recombinant expression and functional characterization of the mouse olfactory receptor mOR256-17 in mammalian cells. Biochemistry 33, 7228-7235 (2011).

179. P Hamel, B Rachet, M Werner, M Grossenbacher, H Vogel, M Forrer, P Ryser, RP Salathé: Individual particle handling in a microfluidic system based on parallel laser trapping.Opt. Lett. 36, 3182-3184 (2011).

180. J Kerschgens, S Renaud, F Schuetz, L Grasso, T Egener-Kuhn, JF Delaloye, HA Lehr, H Vogel, N Mermod: Protein-binding microarray analysis of tumor suppressor AP2a target gene specificity. Plos One 6, e22895 (2011).

181. MA Brun, R Griss, L Reymond, KT Tan, J Piguet, RIRW Peters, H Vogel, K Johnsson: Semisynthesis of fluorescent metabolite sensors on cell surfaces.

J. Am. Chem. Soc. 133, 16325-16242 (2011).

182. S Roizard, C Danelon, G Hassaïne, J Piguet, K Schulze, R Hovius, R Tampe, H Vogel: Activation of G Protein Coupled Receptors in native plasma membranes supported on beads.J. Am. Chem. Soc. 133, 16868-16874 (2011)

183. T Sandén, R Wyss, C Santschi, G Hassaïne, C Deluz, OJF Martin, S Wennmalm, H Vogel: A zeptoliter volume-meter for analysis of single protein molecules.

NanoLetters 12, 370-375 (2012).

184. K Corin, H Pick, P Baaske, BI Cook, S Duhr, CJ Wienken, D Braun, H Vogel, S Zhang: Insertion of T4-lysozyme (T4L) can be a useful tool for studying olfactory-related GPCRs. Mol. Biosystems 8, 1750-1759 (2012)

185. S Yuan, H Vogel, S Filipek: The role of water and sodium ions in the activation of the m-opioid receptor. Angew Chem Int Ed 52, 10112-10115 (2013).

186. Horst Pick, Samuel Terrettaz, Olivia Baud, Ouahiba Laribi, Cathrinn Briken, Horst Vogel: Monitoring proliferative activities of hormone-like odorants in human breast cancer cells by gene transcription profiling and electrical impedance spectroscopy. Biosens Bioel 50, 431-436 (2013).

187. Menno B. Tol, Cédric Deluz, Gherici Hassaine, Alexandra Graff, Henning Stahlberg, Horst Vogel: Thermal unfolding of a mammalian pentameric ligand-gated ion channel proceeds at consecutive, distinct steps. J. Biol. Chem., 288, 5756-5769 (2013).

188. Gherici Hassaine, Cedric Deluz, Menno B. Tol, Xiao-Dan Li, Alexandra Graff, Horst Vogel, Hugues Nury: Large scale expression and purification of the mouse 5-HT3 receptor. Biochim Biophys Acta 1828, 2544-2552 (2013).

189. Luigino Grasso, Romain Wyss, Joachim Piguet, Michael Werner, Gherici Hassaine, Ruud Hovius, Horst Vogel: Downscaling the analysis of complex transmembrane signaling cascades to closed attoliter volumes. Plos One 8, e70929 (2013).

190. Michael Werner, Christoph Kuratli, Rainer E Martin, Remo Hochstrasser, David Wechsler, Thilo Enderle, Alexander I Alanine, Horst Vogel: Seamless Integration of Dose‐Response Screening and Flow Chemistry: Efficient Generation of Structure–Activity Relationship Data of β‐Secretase (BACE1) Inhibitors. Angew Chem Int Ed 53, 1704-1708 (2014).

191. Liang Qiao, Elena Tobolkina, Andreas Lesch, Alexandra Bondarenko, Xiaoqin Zhong, Baohong Liu, Horst Pick, Horst Vogel, Hubert H. Girault: Anal Chem 86, 2033-2041 (2014).

192. Romain Wyss, Luigino Grasso, Camille Wolf, Wolfgang Grosse, Davide Demurtas, Horst Vogel: Molecular and dimensional profiling of highly purified extracellular vesicles by fluorescence fluctuation spectroscopy. Anal Chem 86, 7229-7233 (2014).

193. Gherici Hassaine, Cedric Deluz, Luigino Grasso, Menno B. Tol, Ruud Hovius, Alexandra Graff, Henning Stahlberg, Takashi Tomizaki, Aline Desmyter, Christophe Moreau, Xiao-Dan Li, Frédéric Poitevin, Horst Vogel, Hugues Nury: X-ray structure of the mouse serotonin 5-HT3 receptor. Nature 512, 276-281 (2014).

194. Shuguang Yuan, Slawomir Filipek, Krystof Palczewski, Horst Vogel: Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway. Nature Commun 5, 4733 (2014).

195. M Werner, R Palankar, L Arm, R Hovius, H Vogel: Microfluidic single-cell analysis with affinity-beads. Small 11, 2607-2613 (2015).

196. Shuguang Yuan, Zhenquan Hu, Slawomir Filipek, Horst Vogel: W246 opens a gate for a continuous intrinsic water pathway during activation of the adenosine A2A receptor. Angew Chem Int Ed 54, 556-559 (2015).

197. Felipe O Bendezu, Vincent Vincenzetti, Dimitrios Vavylonis, Romain Wyss, Horst Vogel, Sophie G Martin: Spontaneous Cdc42 polarization independent of GDI-mediated extraction and actin-based trafficking. PLOS Biology 13, e1002097 (2015).

198. Shuguang Yuan, Krzystof Palczewski, Qian Peng, Michal Kolinski, Horst Vogel, Slawomir Filipek: The mechanism of ligand-induced activation or inhibition of m- and k-opioid receptors. Angew Chem Int Ed 54, 7560-7563 (2015).

199. Luigino Grasso, Romain Wyss, Lorenz Wedenauer, Ashwin Thampi, Davide Demurtas, Michel Prudent, Niels Lion, Horst Vogel: Molecular screening of cancer-derived exosomes by surface plasmon resonance spectroscopy. Anal Bioanal Chem 407, 5425-5432 (2015).

200. Olivia Baud, Shuguang Yuan, Luc Veya, Slawomir Filipek, Horst Vogel, Horst Pick: Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles. Sci Rep 5, 14948 (2015).

201. Luc Veya, Joachim Piguet, Horst Vogel: Single molecule imaging deciphers the relation between mobility and signalling of a prototypical G protein-coupled receptor in living cells. J Biol Chem 290, 27723-27735 (2015).

202. Mikhail Kudryashev, Daniel Castano-Diez, Cedric Deluz, Gherici Hassaine, Luigino Grasso, Alexandra Graf-Meyer, Horst Vogel, Henning Stahlberg: The structure of the mouse serotonin 5-HT3 receptor in lipid vesicles. Structure 24, 165-170 (2016).

203. C Grandclement, H Pick, H Vogel, W Held: NK cells respond to haptens by the activation of calcium permeable plasma membrane channels. PLOS One 11, e0151031 (2016).

204. Shuguang Yuan, Slawomir Filipek, Horst Vogel: A gating mechanism of the serotonin 5-HT3 receptor. Structure 24, 816-825 (2016).

205. S Yuan, Q Peng, K Palczewski, H Vogel, S Filipek: Mechanistic studies on the stereoselectivity of the serotonin 5-HT1A receptor. Angew Chem Int Ed 55, 8661-8665 (2016).

206. S Yuan, SHC Chan, H Vogel, S Filipek, RC Stevens, K Palczewski: The molecular mechanism of P2Y1 receptor activation. Angew Chem Int Ed 55, 10331-10335 (2016).

207. Shuguang Yuan, Stephen HC Chan, Slawomir Filipek, Horst Vogel: PyMol and Inkscape bridge the data and the data visualization. Structure 24, 2041-2042 (2016).

208. J Rheinberger, G Hassaine, M Chami, H Stahlberg, H Vogel, X Li: Two-dimensional crystallization of the mouse serotonin 5-HT3A receptor. Micron 92, 19-24 (2017).

209. G Hassaïne, … , H Vogel, H Nury: Expression, biochemistry, and stabilization with camel antibodies of membrane proteins: case study of the mouse 5-HT3 receptor. Membrane Protein Structure and Function Characterization, 139-168. Humana Press (2017).

210. HC Stephen Chen, J Wang, K Palczewski, S Filipek, H Vogel, ZJ Liu, S Yuan: Exploring a new ligand binding site of G protein-coupled receptors. Chemical Science 9, 6480 (2018).

211. H Pick, AC Alves, H Vogel: Single-vesicle assays using liposomes and cell-derived vesicles: From modelling complex membrane processes to synthetic biology and biomedical applications. Chemical Reviews 118, 8598-8654 (2018). (Invited review).

212. HC Stephen Chan, Y Li, T Dahoun, H Vogel, S Yuan: New binding sites, new opportunities for GPCR drug discovery. Trends Biochem Sci 44, 312-330 (2019).

213. S Yuan, T Dahoun, M Brugarolas, H Pick, S Filipek, H Vogel: Computational modeling of the olfactory receptor Olfr73 suggests a molecular basis for low potency of olfactory receptor-activating compounds. Commun Biol 2,141 (2019).

214. HCS Chan, Y Li, T Dahoun, H Vogel, S Yuan: Advancing drug discovery via artificial intelligence. Trends Pharmacol Sci 40, 592-604 (2019). doi:10.1016/j.tips.2019.06.004

215. HCS Chan, Y Xu, L Tan, H Vogel, J Cheng, D Wu, S Yuan: Enhancing the Signaling of GPCRs via Orthosteric Ions. ACS Central Science 6, 274-282 (2020).

216. NM Barnes, …, H Vogel, SW Watts, D Hoyer: International Union of Pharmacology classification of receptors for 5-hydroxytryptamine; pharmacology and function. Pharmacol Rev, 73 (1), 310-520 (2021)

217. Y Zhang, PM Dijkman, R Zou, M Zandl-Lang, RM Sanchez, L Eckhardt-Strelau, H Köfeler, H Vogel, S Yuan, M Kudryashev: Asymmetric opening of the homopentameric 5-HT_3A serotonin receptor in lipid bilayers. Nature Commun. 12 (1), 1-15 ( 2021).

218. M Brugarolas, T Dahoun, G Navarro, H Vogel, H Pick: A novel functional role of mouse Olfr15 in skeletal muscle differentiation. (Ready for submission. Waiting for patent application).

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