allosteric agonist

Cinacalcet (AMG 073) 是口服有活性的Ca receptor (CaR)激动剂，用于研究心血管疾病。

ATI-2341 acetate(1337878-62-2 free base) 是一种有效的 CXCR4 变构激动剂，它激活 Gα1 而不是 Gα13。 ATI-2341 acetate 激活抑制性异源三聚体 G 蛋白 (GI) 以促进对 cAMP 产生的抑制并诱导钙动员。

Cinacalcet metabolite M4 (Rarechem AL BW 1078) 是 Cinacalcet 的代谢物。Cinacalcet 是具有活性的 Ca receptor 激动剂，可用于心血管疾病。

RVD-Hpα acetate(1193362-76-3 free base) 是人血加压素的 N 末端延伸形式，可作为选择性 CB1 受体激动剂。增加体外表达 CB1 受体的细胞中的细胞内 Ca2+ 水平。也是高亲和力 CB2 正变构调节剂 (Ki = 50 nM)。

LUF6096 (CF-602) 是一种有效的腺苷 A3 受体 (adenosine A3 receptor) 变构增强剂。LUF6096 对任何腺苷受体显示出低正构亲和力。LUF6096 在心肌缺血 再灌注损伤中显示出保护作用。

BMT-145027 是一种 mGluR5 的正变构调节剂，没有内在的激动剂活性 (EC50 = 47 nM)。

4-CMTB 是选择性的游离脂肪酸受体 2(FFA2 GPR43)的激动剂以及正变构调节剂 (pEC50=6.38)。

VU0155041 是一种选择性的mGluR4正变构调节剂，有用于帕金森病的研究潜力，对人和大鼠 mGluR4 的EC50值分别为 798 和 693 nM。

Fenobam 是可口服的、可穿过血脑屏障的 mGluR5拮抗剂，具有抗焦虑活性，在大鼠和人重组 mGlu5 受体上的 Kd 值分别 54 和 31 nM。它有反向激动剂活性，可阻断 mGlu5 受体活性，IC50为 84 nM。

VU0119498 是泛 GqmAChR M1、M3和M5的正变构调节剂，具有抗糖尿病活性，EC50值分别为 6.04、6.38 和 4.08 µM。

GPR40/FFAR1 modulator 1是一种针对Gq偶联的游离脂肪酸受体1 (GPR40/FFAR1) 的激动剂以及异构调节剂。

Ogerin 是选择性 GPR68正向别构调节剂(pEC50:6.83)。它能够抑制小鼠对恐惧记忆的回忆。它对 A2A 受体具有适中的拮抗作用(Ki:220 nM)。对 5-HT2B 受体的拮抗作用较弱(Ki:736 nM)。

nAChR agonist 1 (DUN71755) 是一种脑渗透性和口服有效的正变构 α7 烟碱乙酰胆碱受体 (α7 nAChR) 调节剂。它在 Ca2+中，对内源性表达 α7 nAChR 的人 IMR-32 神经母细胞瘤细胞的EC50为 0.32 μM。它可用于阿尔茨海默病的研究。

TBPB 是变构 M1 mAChR 激动剂，EC50值为289nM，可在大鼠中调节淀粉样蛋白加工并产生抗精神病样活性。

L-838417 D9 (C-21191) 是 L-838417 的氘代物。其中L-838417 是亚型选择性GABAA 正变构调节剂，在 α2, α3 和 α5 亚型中作为部分激动剂。

NCGC00229600 是促甲状腺激素受体 (TSHR) 的变构反向激动剂。 NCGC00229600 抑制 TSH 和刺激 TSHR 的内源性激活抗体，可用于格雷夫斯病的研究。

4BP-TQS 是 α7nAChR 变构激动剂。它利用变构跨膜位点激活 nAChRs。

FzM1.8 是变构 FZD4 激动剂，pEC50 为 6.4。 FzM1.8 与 FZD4 结合，在没有任何 WNT 配体的情况下促进 TCF/LEF 转录活性，并激活 WNT/β-catenin 通路[1]。

DFPQ是一种有效且选择性偏向β-arrestin的负向变构调节剂（NAM），作用于β2-adrenergic receptor。DFPQ能够选择性抑制β-arrestin与β2AR的相互作用，而不影响由β-agonist促进的cAMP产生。DFPQ在气道平滑肌中减弱β2AR的功能性脱敏，增强β-agonist在慢性β-agonist治疗条件下维持支气管舒张和抑制细胞迁移的能力。

GAT100 is a potent and covalent negative allosteric modulator (NAM). GAT-100 behaved as a robust positive allosteric modulator of binding of orthosteric agonist CP55,940. This novel covalent probe can serve as a useful tool for characterizing CB1R allosteric ligand-binding motifs.

GAT229 is a positive allosteric modulator of cannabinoid receptor 1 (CB1) and the S-(-) enantiomer of the CB1 modulator GAT211. It does not activate the receptor on its own but enhances the binding and activity of CB agonists. GAT229 (1 μM) enhances the binding of the CB1 full agonist CP 55,940 to CHO cells expressing human recombinant CB1 (hCB1), as well as the activity of 2-arachidonoyl glycerol , arachidonoyl ethanolamide , and CP 55,940 in arrestin2 recruitment assays and increases ERK1/2 and PLCβ3 phosphorylation in HEK293 cells expressing hCB1. GAT229 (1 μM) enhances depolarization-induced suppression of excitation but does not inhibit excitatory postsynaptic currents (EPSCs) in murine autaptic hippocampal neurons. GAT229 (0.2%, topical) reduces intraocular pressure by 5.8 and 7.7 mm Hg after 6 and 12 hours, respectively, in a transgenic mouse model of ocular hypertension using nose, ear, eye mutation (nee) mice.

mGlu4 receptor agonist 1 (compound 62) is a highly effective positive allosteric modulator of mGlu4 receptors, displaying an EC 50 of 308 nM. Additionally, it exhibits noteworthy anxiolytic and antipsychotic properties [1].

AP5 sodium 是选择性的、有效的、口服具有活力的 GPR40 受体激动剂，对内源性配体 (AgoPAM) 表现出正向变构调节效果。AP5 sodium 在大鼠和人肌醇一磷酸 (IP1) 实验中作用于 GPR40 受体，他们的 EC50值分别为 0.49 nM 和 0.8 nM。AP5 sodium 表现出研究 II 型糖尿病的潜能。

N-terminally extended form of human hemopressin that acts as a selective CB1 receptor agonist. Increases intracellular Ca2+ levels in cells expressing CB1 receptors in vitro. Also high affinity CB2 positive allosteric modulator (Ki = 50 nM).

ATI-2341 is an effective functionally selective allosteric agonist for the c-x-c chemokine receptor type 4 (CXCR4), which ACTS as a biased ligand in favor of G G G G G 1 activation instead of G G G G G 13.ATI-2341 activates the inhibitory heterotrimer G p

CVN636，作为口服有效的选择性mGluR7变构激动剂，其对humGluR7的EC50为7 nM，并显示出良好的中枢神经系统（CNS）通透性。

AZ7976 (Compound 42) 是一种针对 Relaxin Family Peptide Receptor 1（RXFP1）的高选择性激动剂 (pEC50 > 10.5)。该化合物通过别构机制增强 RXFP1 的 cAMP 信号传导，从而增加心率。可用于心血管疾病研究领域。

Milbemectin is composed of 30% milbemycin A3 and 70% milbemycin A4, exhibiting acaricidal and nematocidal properties effective against adult spider mites, their eggs, and C. elegans, with IC50 values of 5.3, 41.1, and 9.5 µg ml, respectively. It functions as an allosteric agonist of the Drosophila RDL GABA receptor, and demonstrates efficacy against the pinewood nematode, B. xylophilus, with an LC20 of 0.0781 mg liter.

Mevidalen, also known as LY3154207, is a novel, potent, and subtype selective human D1 positive allosteric modulator (PAM) with minimal allosteric agonist activity (EC50 = 3 nM). In contrast to orthosteric agonists, LY3154207 showed a distinct pharmacological profile without a bell-shaped dose-response relationship or tachyphylaxis in preclinical models. Identification of a crystalline form of free LY3154207 from the discovery lots was not successful. Instead, a novel cocrystal form with superior solubility was discovered and determined to be suitable for development. LY3154207 is now in clinical development as a potential first-in-class D1 PAM for Lewy body dementia..

RVD-Hpα TFA is the N-terminally extended form of human hemopressin that acts as a selectiveCB1receptoragonist. RVD-Hpα TFA increases intracellular Ca2+levels in cells expressingCB1receptors in vitro. RVD-Hpα TFA also high affinityCB2positive allosteric modulator (Ki=50 nM).

Smoothened (SMO) is a GPCR-like receptor which, with Patched, mediates hedgehog signaling to regulate gene expression through the Gli transcription factors. 20(S)-hydroxy Cholesterol (20(S)-OHC) is an oxysterol which binds SMO and activates hedgehog signaling (EC50 = 3 μM), and this activation is selective for the nat-20(S)-OHC enantiomer. Nat-20(S)-OHC synergizes with the SMO agonist SAG, suggesting an allosteric effect. Nat-20(S)-yne is a form of nat-20(S)-OHC with a terminal alkyne group, which can be used in linking reactions known as click chemistry. Click chemistry involves highly dependable and specific azide-alkyne bioconjugation reactions and can be used to capture or immobilize bioactive molecules. Thus, nat-20(S)-yne has been conjugated with magnetic beads to demonstrate that nat-20(S)-OHC directly binds SMO.

VCP-746 is a potent adenosine A2B receptor agonist that stimulates anti-fibrotic signalling. VCP746 reduces hypertrophy in a rat neonatal cardiac myocyte model. VCP746 is a hybrid molecule consisting of an adenosine moiety linked to an adenosine A1 receptor (A1AR) allosteric modulator moiety. At the A1AR, VCP746 mediated cardioprotection in the absence of haemodynamic side effects such as bradycardia.

SS-RJW100 is an enantiomer of RJW100, known as a racemic agonist that targets two nuclear receptors: liver receptor homolog 1 (LRH-1) and steroidogenic factor 1 (SF-1). In vitro experiments reveal that SS-RJW100 promotes the recruitment of coregulator protein fragments and enhances the interaction with the transcriptional intermediary factor 2 (Tif2) coactivator specifically for LRH-1. Additionally, SS-RJW100 disrupts the allosteric activation networks of LRH-1, displaying suboptimal thermal stability [1] [2].

Org-29647, an allosteric modulator of the CB1 receptor, significantly increases the binding of the CB1 receptor agonist.

FFA2 allosteric agonist. Inhibits forskolin-induced cAMP increase and stimulates 35SGTPγS binding in biochemical assays (pEC50 values are 6.9 and 7.23, respectively). Binds at allosteric binding site. In functional assays, displays positive allosteric modulation of FFA-induced Gi signaling and negative allosteric modulation of FFA-induced Gq/G11 signaling. Inhibits lipolytic effect of isoproterenol (pEC50 = 5.03) and induces migration of human neutrophils in vitro. Bolognini et al (2016) A novel allosteric activator of free fatty acid 2 receptor displays unique Gi-functional bias. J.Biol.Chem. 291 18915 PMID:27385588 |Sergeev et al (2017) A single extracellular amino acid in free fatty acid receptor 2 defines antagonist species selectivity and G protein selection bias. Sci.Rep. 7 13741 PMID:29061999

VU0424465 is a mGlu5-selective allosteric agonist.

Basmisanil (RG1662) 是高度选择性GABAAα5负调节剂，用于治疗与唐氏综合症相关的认知障碍。

MmTx1毒素是一种调节变构性GABAA受体活性的化合物，它能够提升GABAA受体对激动剂的反应性。

nAChR agonist CMPI hydrochloride is a potent and selective positive allosteric modulator (PAM) of nAChR containing a α4:α4 subunit interface. nAChR agonist CMPI hydrochloride enhances the response of (α4) 3 (β2) 2 nAChR to ACh (10 μM) with an EC 50 of 0.26 μM. nAChR agonist CMPI hydrochloride has potential for the research of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity.

positive allosteric modulator allosteric agonist of mGlu4 receptor

TASP0433864 is a positive allosteric modulator of metabotropic glutamate 2 receptor with EC50 values of 199 and 206 nM at human and rat mGlu2 receptors, respectively, without exerting agonist activity at rat mGlu2 receptor.

(-)-(S)-B-973B 是一种有效的别构激动剂和 α7 nAChR 的正向别构调节剂，可用于缓解疼痛的研究。

LY2119620 是人 M2 和 M4 毒蕈碱乙酰胆碱受体的特异性变构激动剂。

AMN082 free base 是 mGluR7选择性激动剂，口服有活性，能够透过血脑屏障，可通过跨膜区的变构位点直接激活受体信号。在表达 mGluR7 的转染哺乳动物细胞上，它能够有效抑制 cAMP 积累并刺激 GTPγS 结合。它能够选择性针对 mGluR 的其他亚型及选择性离子型谷氨酸受体。具有抗抑郁活性。

MRGPRX1 agonist 2 (compound 1a) 是有效的Mas 相关 G 蛋白偶联受体 X1 (MRGPRX1)的正变构调节剂（EC50 = 0.48 μM）。MRGPRX1 agonist 2 具有用于神经性疼痛的研究潜力。

ATI-2341 是 C-X-C 趋化因子受体 4 型功能选择性变构激动剂，作为偏向配体有利于 Gα1 激活。它是一种变构激动剂，可激活抑制性异源三聚体 G 蛋白 (Gi) 以促进抑制 cAMP 产生并诱导钙动员。

Org 27569 是一种 CB1 receptor 别构调节剂，可以增加激动剂与 CB1 结合，能够抑制激动剂诱导的 CB1 信号通路。

SOMCL-668 是一种选择性和有效的 sigma-1 受体变构调节剂，对选择性 sigma-1 激动剂 PRE084 诱导的社会缺陷和认知障碍的改善表现出积极调节作用，并具有抗癫痫活性，可用于精神疾病研究。