allosteric agonist

Cinacalcet (AMG 073) is an orally active, allosteric Ca receptor (CaR) agonist used in the treatment of cardiovascular disease.

ATI-2341 acetate is an effective allosteric agonist of CXCR4, it activates Gα1 instead of Gα13. ATI-2341 acetate activates inhibitory heterotrimeric G protein (GI) to promote the inhibition of cAMP production and induce calcium mobilization.

Cinacalcet metabolite M4 (Rarechem AL BW 1078) is a metabolite of Cinacalcet. Cinacalcet is an allosteric agonist of Ca receptor.

RVD-Hpα acetate is the 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

LUF6096 (CF-602) is a potent allosteric enhancer of the adenosine A3 receptor, exhibiting the capability to enhance agonist binding allosterically while demonstrating low orthosteric affinity across adenosine receptors. It displays protective effects in myocardial ischemia reperfusion injury.

BMT-145027 is a positive allosteric modulator of mGluR5 without inherent agonist activity (EC50 = 47 nM).

4-CMTB is a selective agonist of FFA2 and GPR43.It also is a positive allosteric modulator (pEC50=6.38).

VU0155041 is an effective and positive allosteric modulator/allosteric agonist at mGlu4 receptors (EC50: 798/693 nM, at human/rat).

Fenobam shows inverse agonist activity which blocks the mGlu5 receptor basal activity(IC50: 84 nM). Fenobam has anxiolytic activity. Fenobam is a selective and non-competitive mGluR5 antagonist acting at an allosteric modulatory site (Kd values are 54 and 31 nM for rat and human recombinant mGlu5 receptors, respectively).

VU0119498 is a M1 muscarinic receptor agonist (EC50 = 3.1 μM) and pan mAChR M3, M5 positive allosteric modulator (PAM),and is a neuroprotective agent.

Basmisanil (RG1662) is a negative allosteric modulator/inverse agonist of GABAAα5 receptors.Formulations containing basmisanil are in clinical trials for the treatment of cognitive impairments associated with Down syndrome.

Ogerin is a selective GPR68 positive allosteric modulator (pEC50: 6.83) that blocks recall in fear conditioning in mice. It exhibits inverse agonist and antagonist activity (Ki, 220 nM) at the A2A receptor and weak antagonist activity (Ki, 736 nM) at the 5-HT2B receptor.

LY2119620 is a specific, and allosteric agonist of human M2 and M4 muscarinic acetylcholine receptors.

(-)-(S)-B-973B is an effective allosteric agonist and positive allosteric modulator of α7 nAChR.

AMN082 free base is a metabotropic glutamate receptor 7 allosteric agonist.

TBPB, an allosteric M1 mAChR agonist, is an [iso]propyl (2-{4-methoxy-3-[3-(4-methylpiperidin-1-yl)propoxy]phenyl}ethyl)carbamate exhibiting a molar mass of 430.6 g mol.

CYM-5520 is a noncompetitive allosteric agonist of S1P2

L-838417 D9 (C-21191) is a novel deuterated subtype-selective GABAA positive allosteric modulator, acting as a partial agonist at α2, α3 and α5 subtypes[1].

4BP-TQS is an allosteric agonist of α7 nAChRs.

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.

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, a potent and selective allosteric agonist for the mGluR7 receptor, exhibits oral activity and CNS permeability [1], with an EC50 of 7 nM for human mGluR7.

mGlu4 receptor agonist 1 (compound 62) is a potent positive allosteric modulator of mGlu4 receptors, with an EC50 of 308 nM, and exhibits significant anxiolytic and antipsychotic properties [1].

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).

AP5 sodium is a selective, potent, orally active GPR40 receptor agonist that exhibits positive allosteric modulation of endogenous ligands (AgoPAM). sodium exhibits potential for the study of type II diabetes.

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 selective CB1 receptor agonist. RVD-Hpα TFA increases intracellular Ca 2+ levels in cells expressing CB1 receptors in vitro. RVD-Hpα TFA also high affinity CB2 positive allosteric modulator (K i =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].

Micrurotoxin 1 (MmTx1 toxin) acts as an allosteric modulator of GABA A receptors, enhancing the receptor's sensitivity to its agonist [1].

GPR40/FFAR1 modulator 1 is a Gq-coupled free fatty acid receptor 1 (GPR40/FFAR1) agonist and allosteric modulator.

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.

CMPI hydrochloride, a potent and selective nAChR agonist, functions as a positive allosteric modulator (PAM) specifically targeting the α4:α4 subunit interface of the nAChR. It enhances the response of the (α4)3(β2)2 nAChR to acetylcholine (ACh) (10 μM) with an EC 50 of 0.26 μM. With its potential for researching nicotine dependence and various neuropsychiatric conditions linked to reduced brain cholinergic activity, CMPI hydrochloride stands as a significant compound in neurological research.

positive allosteric modulator/allosteric agonist of mGlu4 receptor

Org 27569, an allosteric modulator of cannabinoid CB1 receptor, can induce a CB1 receptor state that is characterized by decreased inverse agonist affinity and enhanced agonist affinity.

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.

MRGPRX1 agonist 2 (compound 1a) is a potent positive allosteric modulator of Mas-related G protein-coupled receptor X1 (MRGPRX1) with an EC50 value of 0.48 μM, and has potential for use in neuropathic pain research [1].

ATI-2341, pepducin targeting the C-X-C chemokine receptor type 4 (CXCR4), is an allosteric agonist activating the inhibitory heterotrimeric G protein (Gi) to promote inhibition of cAMP production and induce calcium mobilization.

GSK-1034702 HCl is a potent M1 receptor allosteric agonist.

NCGC00229600 is an allosteric inverse thyrotropin receptor (TSHR) agonist. NCGC00229600 inhibits both TSH and stimulating antibody activation of TSHRs endogenously and can be used in Graves' disease studies.

AC260584 is an allosteric agonist of the M1 muscarinic receptor with a pEC50 of 7.6.

MRGPRX1 agonist 3 (compound 1f) is a potent positive allosteric modulator of Mas-related G protein-coupled receptor X1 (MRGPRX1) with an EC50 of 0.22 μM, and it can be used for neuropathic pain research[1].

nAChR agonist 1 (DUN71755) is a brain-permeable and orally efficacious positive allosteric α7 nicotinic acetylcholine receptor (α7 nAChR)modulator.

(Z)-Leukadherin-1 (ADH-503 free base) is an allosteric agonist of CD11b.

α-Conotoxin MrIC is a biased agonist selective for the α7 nicotinic acetylcholine receptor (nAChR), with activation contingent upon the presence of type II positive allosteric modulators, such as PNU120596. It is utilized to investigate neurological disorders and delineate the pharmacological characteristics of the α7nAChR [1].

ATI-2341 is a potent, functionally selective allosteric agonist of the C-X-C chemokine receptor type 4 (CXCR4), acting as a biased ligand that prefers Gαi activation over Gα13. This compound activates the inhibitory heterotrimeric G protein (Gi), leading to reduced cAMP production and enhanced calcium mobilization. ATI-2341 effectively mobilizes bone marrow polymorphonuclear neutrophils (PMNs) and hematopoietic stem and progenitor cells (HSPCs) [1] [2].

L838417 is a modulator of the GABAA receptor.