Illuminating the Druggable GPCR-ome

阐明可药物化的 GPCR-ome

• 批准号: 10612133
• 负责人: Bryan L. Roth
• 金额: $ 74.95万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10612133
• 关键词: Arrestins; Award; Cell Line; Chemicals; Chemistry; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communities; Cryoelectron Microscopy; Databases; Development; Docking; Drug Targeting; Electron Microscopy; Engineering; Epinephrine; Funding; G-Protein-Coupled Receptors; G-substrate; Genetic; Genetically Engineered Mouse; Goals; Heart Rate; Human Genome; Individual; Informatics; Infrastructure; Investigation; Learning; Light; Lipids; Memory; Modeling; Molecular Target; Mus; Orphan; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Phase; Physiological; Physiology; Plasmids; Protein Family; Reagent; Reporter; Reporter Genes; Research; Research Personnel; Resource Sharing; Resources; Respiration; Signal Transduction; Specific qualifier value; Structure; Synthesis Chemistry; Technology; Testing; Tissues; Transducers; Viral; Vision; Yeasts; base; cell type; chemical genetics; chemical synthesis; chemokine; computer infrastructure; computerized tools; cryogenics; data resource; data sharing; designer receptors exclusively activated by designer drugs; drug discovery; experimental study; genetic approach; human disease; in vivo Model; large datasets; medical schools; new technology; novel; novel therapeutics; optogenetics; programs; public health relevance; receptor; screening; targeted treatment; therapeutic target; tool

Abstract PROJECT SUMMARY G protein coupled receptors (GPCRs) represent essential molecular targets for a large number of approved as well as investigational medications. Of the 380 or so non-olfactory GPCRs in the human genome around 100 are understudied and/or orphan receptors (oGPCRs). The oGPCRs represent potential therapeutic targets although discovering drugs that modulate them is challenging. Here we will solve the structures of 15-20 oGPCRs using cryogenic electron microscopy (cryo-EM). The solved structures then will serve as templates for structure-guided drug discovery targeting these oGPCRs.

抽象的 项目概要 G 蛋白偶联受体 (GPCR) 代表了大量已批准和研究药物的重要分子靶标。在人类基因组中大约 380 个非嗅觉 GPCR 中，大约有 100 个是待研究和/或孤儿受体 (oGPCR)。 oGPCR 代表了潜在的治疗靶点，尽管发现调节它们的药物具有挑战性。 在这里，我们将使用低温电子显微镜 (cryo-EM) 解析 15-20 个 oGPCR 的结构。 然后，解决的结构将作为针对这些 oGPCR 的结构引导药物发现的模板。

项目成果

Alternative splicing of latrophilin-3 controls synapse formation.

• DOI: 10.1038/s41586-023-06913-9
• 发表时间: 2024-02
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Wang, Shuai;Deleon, Chelsea;Sun, Wenfei;Quake, Stephen R.;Roth, Bryan L.;Suedhof, Thomas C.
• 通讯作者: Suedhof, Thomas C.

In silico design of novel probes for the atypical opioid receptor MRGPRX2.

• DOI: 10.1038/nchembio.2334
• 发表时间: 2017-05
• 期刊: Nature chemical biology
• 影响因子: 14.8
• 作者: Lansu K;Karpiak J;Liu J;Huang XP;McCorvy JD;Kroeze WK;Che T;Nagase H;Carroll FI;Jin J;Shoichet BK;Roth BL
• 通讯作者: Roth BL

How Ligands Illuminate GPCR Molecular Pharmacology.

• DOI: 10.1016/j.cell.2017.07.009
• 发表时间: 2017-07-27
• 期刊: Cell
• 影响因子: 64.5
• 作者: Wacker D;Stevens RC;Roth BL
• 通讯作者: Roth BL

Report and Application of a Tool Compound Data Set.

• DOI: 10.1021/acs.jcim.7b00343
• 发表时间: 2017-11-27
• 期刊: Journal of chemical information and modeling
• 影响因子: 5.6
• 作者: Butler KV;MacDonald IA;Hathaway NA;Jin J
• 通讯作者: Jin J

Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys

• DOI: 10.1038/s41593-020-0661-3
• 发表时间: 2020-07-06
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Nagai, Yuji;Miyakawa, Naohisa;Minamimoto, Takafumi
• 通讯作者: Minamimoto, Takafumi