agonism

SB 258719 是高亲和力的、选择性的5-HT7受体拮抗剂，pKi 为7.5。SB 258719在癌症和神经系统疾病领域有研究价值。

KN-62 是一种选择性的、可逆的钙调蛋白依赖性蛋白激酶 II (CaMK-II) 抑制剂，直接与 CaMK-II 酶的钙调蛋白结合位点结合，对大鼠脑 CaMK-II 的IC50值为 0.9 μM。它是非竞争性的P2X7受体拮抗剂，IC50约为 15 nM。

AZD9496 maleate is a highly potent and selective antagonist of the estrogen receptor alpha (ERα), exhibiting an IC50 value of 0.28 nM. This compound, AZD9496 maleate, is an orally bioavailable selective estrogen receptor degrader (SERD).

Tirzepatide (LY3298176) Acetate(2023788-19-2 free base) 是一种新分子，能够通过结合葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1）受体的双重激动作用来控制血糖水平。[3]

OP-3633 is an effective and selective steroidal glucocorticoid receptor (GR) antagonist (IC50: 29 nM). OP-3633 shows low progesterone receptor (PR) agonism and androgen receptor (AR) antagonism. It also has an inhibition of GR transcriptional activity.

Romergoline 是一种新合成的麦角碱衍生物，具有独特的药理作用，在正常动物中表现出完全的多巴胺(DA)拮抗作用，而在“去神经”动物模型中表现出完全的DA 拮抗作用。

GSK-7227是一种代表过氧化物酶体增殖物激活受体δ（PPARδ）的新型部分激动剂，通过上调骨骼肌细胞中PPARδ靶基因——特别是肉碱棕榈酰转移酶1a（CPT1a）和丙酮酸脱氢酶激酶4（PDK4）的表达，表现出强效的部分激动活性。GSK-7227在调节骨骼肌代谢与能量稳态方面具有潜在作用。

Org GC 94是一种具有精神活性的小分子化合物，隶属于四环类抗抑郁药（tetracyclic antidepressant, TeCA）治疗家族，被广泛表征为去甲肾上腺素能和特异性5-羟色胺能抗抑郁药（noradrenergic and specific serotonergic antidepressant, NaSSA），并在临床上证实具有抗抑郁、抗焦虑、催眠、止吐、促食欲及抗组胺等多种药理作用。Org GC 94在作用机制上表现为H1、5-HT1D、5-HT2A、5-HT2B、5-HT2C、5-HT3、5-HT6、5-HT7、α1-肾上腺素能及α2-肾上腺素能受体的拮抗剂或反向激动剂，同时抑制去甲肾上腺素再摄取；其对H1受体具有高亲和力的反向激动活性，与镇静和体重增加相关；对毒蕈碱型乙酰胆碱受体几乎无亲和力，因此不表现出抗胆碱能不良反应。

COR659 是一种有效的 GABAB 的阳性变构调节剂。COR659具有缓解大鼠对酒精和巧克力成瘾的作用。

NXN-188 是一种一流的、双重作用的小分子化合物，结合了神经型一氧化氮合酶 (nNOS) 抑制和 5-HT 受体激动剂，目前正处于急性偏头痛治疗的开发阶段。

SC-17599 在乙酸诱导的扭体实验和热水尾部抽回试验中显示出剂量依赖性的镇痛效果。此化合物还以剂量依赖和纳曲酮敏感的方式诱导Straub尾反应，与吗啡的效果类似。与吗啡不同的是，高剂量的SC-17599并不影响运动活动。总体而言，SC-17599表现出选择性的μ阿片受体激动作用，其行为效应与吗啡相似，尽管存在一些差异。

5-Iodowillardiine 是一种针对特定 kainate 受体亚基的选择性激动剂，可强效激活含 GluK1（GluR5）和 GluK5（KA2）的受体，同时对 AMPA 受体活性极低，且对 GluK2（GluR6）亚基无可测激动作用。尽管其在体内具有兴奋毒性神经毒性，5-Iodowillardiine 仍是解析 kainate 受体亚型分布、突触功能及脑和脊髓兴奋性神经传递的重要实验工具。

Aganodine is a guanidine that activates presynaptic imidazoline receptors. Aganodine inhibits the presynaptic release of norepinephrine through its agonism at imidazoline receptors.

BIO592 is a modulator of RORγt. BIO592 triggers inverse agonism of RORγ.

Navafenterol saccharinate (AZD-887 saccharinate) 是一种吸入给药的双重作用分子，兼具高效、选择性且持久的 M3 受体拮抗和 β2 受体激动活性。其对人 M3 受体的 pIC50 为 9.5，对 β2 肾上腺素能受体的 pEC50 亦为 9.5。Navafenterol 可提供持续的支气管保护和抑制唾液分泌作用，并具有良好的心血管安全性，是慢性阻塞性肺疾病研究中的重要候选研究化合物。

(±)-WIN 55,212-2 is a potent aminoalkylindole cannabinoid (CB) receptor agonist with a Ki value of 62.3 and 3.3 nM for human recombinant central cannabinoid (CB1) and peripheral cannabinoid (CB2) receptors, respectively. In contrast, the enantiomer (-)-WIN 55,212-3 acts a partial inverse agonist at CB1 (pIC50 = 5.5) and as a competitive neutral antagonist of CB2, reversing the inverse agonism evoked by SR 144528 (pEC50 = 5.3). (+)-WIN 55,212 (mesylate) is a mixture of the two enantiomers, (+)-WIN 55,212-2 and (-)-WIN 55,212-3.

Fabomotizole hydrochloride (CM346 hydrochloride) 是一种具有抗焦虑和神经保护作用的化合物。

PPARγ phosphorylation inhibitor 1(Compound 10)是一种有效的PPARγ结合剂(IC50=24 nM),能够抑制CDK5介导的PPARγ Ser273磷酸化（IC50=160 nM），具有抗糖尿病活性。

SC13 是一种新型的 mitragynine 类似物，具有低效Muopioid receptor 激动作用，具有麻醉作用和较轻的不良反应。

PPARγ agonist 1 是 PPARγ 的有效激动剂，能够高效的激活 hPPARγ ，并不引起完全激动，进而能够避免不良反应。PPARγ agonist 1 对代谢紊乱相关心血管疾病表现出研究潜力。

OL-135 is a CNS penetrant, highly potent and selective reversible inhibitor of FAAH. OL-135 exhibits analgesic pharmacology in various animal models without the motor impairment associated with direct CB1 agonism.

Fabomotizole, also known as Afobazole, Obenoxazine and CM346, is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions. Its mechanism of action remains poorly defined however, with GABAergic, NGF- and BDNF-release-promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism suggested as potential mechanisms. Fabomotizole was shown to inhibit MAO-A reversibly and there might be also some involvement with serotonin receptors.

Fadolmidine, also known as MPV-2426, is a novel and potent alpha2 -adrenoceptor (alpha2) -AR) agonist developed for spinal analgesia. Fadolmidine displayed high affinity and full agonist efficacy at all three human alpha2-adrenoceptor subtypes (A, B and C) in transfected CHO cells with EC50 values (nM) of 0.4, 4.9 and 0.5, respectively. Fadolmidine inhibited also electrically evoked contractions in rat vas deferens demonstrating the activation of rodent presynaptic alpha2D-adrenoceptors with an EC50 value of 6.4 nM. Moreover, fadolmidine was a full agonist at human alpha1A-adrenoreceptor (EC50 value 22 nM) and alpha1B-adrenoreceptor (EC50 value 3.4 nM) in human LNCaP cells and transfected HEK cells, respectively. Agonism at the alpha1-adrenoceptor was also observed in rat vas deferens preparations although at lower potency (EC50 value 5.6 microM). Fadolmidine demonstrated potent alpha2-adrenoceptor agonist activity also in vivo by inhibiting electrically induced tachycardia i......

PF-04479745, also known as PF-4479745, is a potent and selective 5-HT2C agonist (EC50 = 10 nM). PF-4479745 displayed robust pharmacology in a preclinical canine model of stress urinary incontinence (SUI) and no measurable functional agonism at the key selectivity targets 5-HT2A and 5-HT2B in relevant tissue-based assay systems.