GPR52激动剂HTL0041178的鉴定：一种治疗精神分裂症及相关精神障碍的潜在疗法
The Identification of GPR52 Agonist HTL0041178, a Potential Therapy for Schizophrenia and Related Psychiatric Disorders.
作者信息
Poulter Simon, Austin Nigel, Armstrong Rachel, Barnes Matt, Bucknell Sarah Joanne, Higueruelo Alicia, Banerjee Joydeep, Mead Andy, Mould Richard, MacSweeney Cliona, O'Brien M Alistair, Stott Lisa Alice, Watson Stephen P
机构信息
Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge CB21 6DG, United Kingdom.
Syngene International, Biocon Park, Bommasandra, Bangalore 560099, India.
出版信息
ACS Med Chem Lett. 2023 Mar 14;14(4):499-505. doi: 10.1021/acsmedchemlett.3c00052. eCollection 2023 Apr 13.
Abstract
HTL0041178 (), a potent GPR52 agonist with a promising pharmacokinetic profile and exhibiting oral activity in preclinical models, has been identified. This molecule was the outcome of a judicious molecular property-based optimization approach, focusing on balancing potency against metabolic stability, solubility, permeability, and P-gp efflux.
摘要
HTL0041178（）是一种强效的GPR52激动剂，具有良好的药代动力学特征，且在临床前模型中表现出口服活性。该分子是基于明智的分子特性优化方法的成果，重点在于平衡效力与代谢稳定性、溶解度、渗透性和P-糖蛋白外排。
相似文献
1
The Identification of GPR52 Agonist HTL0041178, a Potential Therapy for Schizophrenia and Related Psychiatric Disorders.GPR52激动剂HTL0041178的鉴定：一种治疗精神分裂症及相关精神障碍的潜在疗法
ACS Med Chem Lett. 2023 Mar 14;14(4):499-505. doi: 10.1021/acsmedchemlett.3c00052. eCollection 2023 Apr 13.
2
Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior.发现强效且可穿透血脑屏障的 GPR52 激动剂，可抑制精神兴奋剂行为。
J Med Chem. 2020 Nov 25;63(22):13951-13972. doi: 10.1021/acs.jmedchem.0c01498. Epub 2020 Nov 16.
3
Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide derivatives as novel GPR52 agonists.新型GPR52激动剂4-唑基-苯甲酰胺衍生物的设计、合成及药理评价
Bioorg Med Chem. 2017 Jun 15;25(12):3098-3115. doi: 10.1016/j.bmc.2017.03.064. Epub 2017 Apr 1.
4
Design and synthesis of 1-(1-benzothiophen-7-yl)-1H-pyrazole, a novel series of G protein-coupled receptor 52 (GPR52) agonists.1-(1-苯并噻吩-7-基)-1H-吡唑的设计与合成，一种新型的 G 蛋白偶联受体 52（GPR52）激动剂系列。
Bioorg Med Chem. 2018 May 1;26(8):1598-1608. doi: 10.1016/j.bmc.2018.02.005. Epub 2018 Feb 10.
5
In the Loop: Extrastriatal Regulation of Spiny Projection Neurons by GPR52.在回路中：GPR52 对棘突投射神经元的纹状体外调节。
ACS Chem Neurosci. 2020 Jul 15;11(14):2066-2076. doi: 10.1021/acschemneuro.0c00197. Epub 2020 Jul 7.
6
β-Arrestin-2-Dependent Mechanism of GPR52 Signaling in Frontal Cortical Neurons.β-arrestin-2 依赖的 GPR52 信号转导在额皮质神经元中的机制
ACS Chem Neurosci. 2020 Jul 15;11(14):2077-2084. doi: 10.1021/acschemneuro.0c00199. Epub 2020 Jul 7.
7
High-throughput virtual screening of potential inhibitors of GPR52 using docking and biased sampling method for Huntington's disease therapy.使用对接和偏向采样方法对亨廷顿舞蹈病治疗中GPR52潜在抑制剂进行高通量虚拟筛选。
Mol Divers. 2024 Oct;28(5):3331-3347. doi: 10.1007/s11030-023-10763-y. Epub 2023 Dec 1.
8
Structural basis of ligand recognition and self-activation of orphan GPR52.孤儿 GPR52 配体识别和自身激活的结构基础。
Nature. 2020 Mar;579(7797):152-157. doi: 10.1038/s41586-020-2019-0. Epub 2020 Feb 19.
9
Anatomical transcriptome of G protein-coupled receptors leads to the identification of a novel therapeutic candidate GPR52 for psychiatric disorders.G蛋白偶联受体的解剖转录组学有助于鉴定一种用于治疗精神疾病的新型候选药物GPR52。
PLoS One. 2014 Feb 28;9(2):e90134. doi: 10.1371/journal.pone.0090134. eCollection 2014.
10
FTBMT, a Novel and Selective GPR52 Agonist, Demonstrates Antipsychotic-Like and Procognitive Effects in Rodents, Revealing a Potential Therapeutic Agent for Schizophrenia.FTBMT，一种新型选择性GPR52激动剂，在啮齿动物中表现出抗精神病样和促认知作用，揭示了一种治疗精神分裂症的潜在治疗药物。
J Pharmacol Exp Ther. 2017 Nov;363(2):253-264. doi: 10.1124/jpet.117.242925. Epub 2017 Aug 29.
引用本文的文献
1
Discovery of 3-((4-Benzylpyridin-2-yl)amino)benzamides as Potent GPR52 G Protein-Biased Agonists.发现3-((4-苄基吡啶-2-基)氨基)苯甲酰胺作为有效的GPR52 G蛋白偏向性激动剂。
J Med Chem. 2024 Jun 13;67(11):9709-9730. doi: 10.1021/acs.jmedchem.4c00856. Epub 2024 May 24.
2
Orphan GPR52 as an emerging neurotherapeutic target.孤儿 GPR52 作为一个新兴的神经治疗靶点。
Drug Discov Today. 2024 Apr;29(4):103922. doi: 10.1016/j.drudis.2024.103922. Epub 2024 Feb 20.
本文引用的文献
1
Characterisation of inverse agonism of the orphan-G protein-coupled receptor GPR52 by cannabinoid ligands Cannabidiol and O-1918.大麻素配体大麻二酚和O-1918对孤儿G蛋白偶联受体GPR52反向激动作用的表征
Heliyon. 2021 Jun 1;7(6):e07201. doi: 10.1016/j.heliyon.2021.e07201. eCollection 2021 Jun.
2
Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior.发现强效且可穿透血脑屏障的 GPR52 激动剂，可抑制精神兴奋剂行为。
J Med Chem. 2020 Nov 25;63(22):13951-13972. doi: 10.1021/acs.jmedchem.0c01498. Epub 2020 Nov 16.
3
Structural basis of ligand recognition and self-activation of orphan GPR52.孤儿 GPR52 配体识别和自身激活的结构基础。
Nature. 2020 Mar;579(7797):152-157. doi: 10.1038/s41586-020-2019-0. Epub 2020 Feb 19.
4
Design and synthesis of 1-(1-benzothiophen-7-yl)-1H-pyrazole, a novel series of G protein-coupled receptor 52 (GPR52) agonists.1-(1-苯并噻吩-7-基)-1H-吡唑的设计与合成，一种新型的 G 蛋白偶联受体 52（GPR52）激动剂系列。
Bioorg Med Chem. 2018 May 1;26(8):1598-1608. doi: 10.1016/j.bmc.2018.02.005. Epub 2018 Feb 10.
5
FTBMT, a Novel and Selective GPR52 Agonist, Demonstrates Antipsychotic-Like and Procognitive Effects in Rodents, Revealing a Potential Therapeutic Agent for Schizophrenia.FTBMT，一种新型选择性GPR52激动剂，在啮齿动物中表现出抗精神病样和促认知作用，揭示了一种治疗精神分裂症的潜在治疗药物。
J Pharmacol Exp Ther. 2017 Nov;363(2):253-264. doi: 10.1124/jpet.117.242925. Epub 2017 Aug 29.
6
Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide derivatives as novel GPR52 agonists.新型GPR52激动剂4-唑基-苯甲酰胺衍生物的设计、合成及药理评价
Bioorg Med Chem. 2017 Jun 15;25(12):3098-3115. doi: 10.1016/j.bmc.2017.03.064. Epub 2017 Apr 1.
7
Lipophilicity and biomimetic properties measured by HPLC to support drug discovery.通过高效液相色谱法测定亲脂性和仿生特性以支持药物研发。
J Pharm Biomed Anal. 2016 Oct 25;130:35-54. doi: 10.1016/j.jpba.2016.04.009. Epub 2016 Apr 8.
8
Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52.发现首个强效、可口服的孤儿 G 蛋白偶联受体 52 的激动剂。
J Med Chem. 2014 Jun 26;57(12):5226-37. doi: 10.1021/jm5002919. Epub 2014 Jun 12.
9
Anatomical transcriptome of G protein-coupled receptors leads to the identification of a novel therapeutic candidate GPR52 for psychiatric disorders.G蛋白偶联受体的解剖转录组学有助于鉴定一种用于治疗精神疾病的新型候选药物GPR52。
PLoS One. 2014 Feb 28;9(2):e90134. doi: 10.1371/journal.pone.0090134. eCollection 2014.
10
Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters.在分子优化中设定预期：常用综合参数的优缺点。
Bioorg Med Chem Lett. 2013 Nov 1;23(21):5980-91. doi: 10.1016/j.bmcl.2013.08.029. Epub 2013 Aug 13.
Zotero 插件