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Targeted therapy! The Capetin Prize winning "Click Chemistry" can be used like this!Targeted therapy! The Nobel Prize winning "Click Chemistry" can be used like this!2025-02-06
33 Results for "
orthosteric site
" in MedChemExpress (MCE) Product Catalog:
Products (33)
33 Results for "orthosteric site" in MCE Product Catalog:
4
4 Cited Publications
Cat. No.: HY-N1910
CAS No.: 20784-60-5
2
2 Cited Publications
Synonyms: AVL-3288; UCI-4083
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CCMI (AVL-3288) is a potent and selective α7 nAChR-positive allosteric modulator, does not bind to or activate α7 nAChRs via the orthosteric site, and causes significant positive modulation of agonist-induced currents at α7 nAChRs. CCMI has potential in CNS diseases with cognitive dysfunction .
Cat. No.: HY-174801
CAS No.: 3117797-30-2
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XL-3156 is a cGAS inhibitor. XL-3156 occupies both allosteric and orthosteric sites simultaneously, and inhibits the interaction and phase separation between cGAS and DNA by stabilizing the closed conformation of the activation loop. XL-3156 can be used in the research of diseases such as autoimmune diseases and inflammation .
Cat. No.: HY-159829
CAS No.: 1803346-98-6
Synonyms: NBI-1117568; HTL-0016878
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Direclidine (NBI-1117568, HTL-0016878) is a selective orthosteric agonist targeting the muscarinic acetylcholine M4 receptor, exhibiting very low affinity for M1, M2, M3, and M5 receptors. It binds to the orthosteric site of the M4 receptor in a non-covalent, competitive manner. Direclidine specifically activates the M4 receptor, inhibiting the release of acetylcholine from striatal cholinergic interneurons, thereby regulating the balance of the dopaminergic system and reducing psychiatric symptoms associated with excessive dopamine release. Direclidine can improve symptoms associated with neuropsychiatric disorders and is used in research on schizophrenia and other neuropsychiatric disorders .
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SR 16832 is a dual-site covalent, orthosteric and allosteric PPARγ antagonist. SR 16832 activates the TGF-β signaling pathway and upregulates the expression of Vimentin and Fibronectin (Fibronectin). SR 16832 is toxic to bronchial epithelium. SR 16832 can be used in research related to type 2 diabetes and pulmonary fibrosis .
Cat. No.: HY-N7683
CAS No.: 89595-66-4
Category:
Flavonoids Monophenols Rosaceae Metabolic Disease Phenols Plants Prunus avium Disease Research Fields Isoflavones
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Cat. No.: HY-174802
CAS No.: 3117797-77-7
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XL-3158 is a selective and cross-species Cyclic GMP-AMP synthase (cGAS) inhibitor (IC50: 11.1 μM for human cGAS, 2.19 μM for mouse cGAS). XL-3158 simultaneously occupy allosteric and orthosteric sites, stabilizing the activation loop in a closed, inactive conformation and thereby attenuating the cGAS-DNA interactions. XL-3158 inhibits cGAS by targeting phase separation. XL-3158 efficiently penetrates cells by inhibiting aggregate formation, effectively reducing the local concentration of cGAS within cells. XL-3158 can be used for the study of cGAS-dependent inflammatory diseases.
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MOMBA is a selective FFA2 (Free Fatty Acid Receptor 2) orthosteric agonist that activates receptor signaling pathways by binding to the orthosteric site of FFA2 with high specificity. MOMBA holds potential for research on metabolic and inflammatory diseases .
Cat. No.: HY-112874
CAS No.: 847998-92-9
Synonyms: BMS-687681
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BMS-681 is an orthosteric antagonist of CC chemokine receptor 2 (CCR2). BMS-681 restricts the movement of the extracellular end of TM6 by stabilizing TM7. TM7 and TM6 are the main components of the orthosteric binding site. BMS-681 can be used to study inflammatory neurodegenerative diseases and cancer .
Cat. No.: HY-146201
CAS No.: 2511632-25-8
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PDE4B/7A-IN-1 is a dual PDE4B/PDE7A inhibitor. PDE4B/7A-IN-1 shows IC50 values of 69.0 μM for PDE4B and 57.0 μM for PDE7A, as well as Ki values of 539 nM for 5-HT1A and 328 nM for 5-HT7. PDE4B/7A-IN-1 shows favorable membrane permeability. PDE4B/7A-IN-1 can be used for the study of cognitive impairment and depression .
Cat. No.: HY-135698
CAS No.: 117339-76-1
Synonyms: M-CAM
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Methocinnamox (M-CAM) a selective and long-acting μ-opioid receptor (MOR) antagonist with a Ki of 0.6 nM. Methocinnamox binds to the orthosteric site of the MOR in a pseudo-irreversible, non-covalent manner, resulting in prolonged receptor blockade that persists until new receptors are synthesized. Methocinnamox acts as a reversible antagonist at both the kappa-opioid receptor (KOR) (Ki = 4.9 nM) and delta-opioid receptor (DOR) (Ki = 2.2 nM), and it exhibits no intrinsic agonist activity at these receptors. Methocinnamox can be used to reverse and prevent opioid overdose and addiction .
Cat. No.: HY-162659
CAS No.: 3051498-44-0
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β2AR ligand 1 (Compound 4) is a homobivalent bitopic ligand for β2 adrenergic receptor (β2AR) on the orthosteric binding site (OBS) and the metastable binding sites (MBS) .
Cat. No.: HY-174147
CAS No.: 91981-93-0
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GABAB receptor antagonist 4 (Compound 28) is a GABAB receptor antagonist. GABAB receptor antagonist 4 can inhibit GABA-induced G protein activation. GABAB receptor antagonist 4 competitively binds to the orthosteric site of GABAB receptor. GABAB receptor antagonist 4 can be used to study GABAB receptor-related neurological diseases .
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VUF-6884 (Compound 7j) is a histamine receptor (Histamine Receptor) ligand with activity toward human H4R and H1R. Its pEC50 and pKi values against human H4R are 7.70 and 7.55, respectively, while those against human H1R are 8.17 and 8.11, respectively. VUF-6884 competitively binds to the orthosteric binding site of human H4R to displace histamine, and exhibits inverse agonist activity at human H1R .
Cat. No.: HY-189243
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P2Y2R antagonist-2 is an antagonist of the P2Y2 receptor (P2Y2R), with a pKi value of 6.53 for human P2Y2R. P2Y2R antagonist-2 blocks UTPγS (HY-137603)-induced calcium mobilization, binds to the orthosteric site of P2Y2R to displace fluorescent antagonist ligands, and forms unique binding interactions. P2Y2R antagonist-2 has no structural alerts, exhibiting low lipophilicity and high lipophilic efficiency. P2Y2R antagonist-2 can be used in studies related to astrocytoma and inflammation .
Cat. No.: HY-180554
CAS No.: 300587-89-7
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UCB1244283 is a synaptic vesicle glycoprotein 2A (SV2A) allosteric modulator. UCB1244283 binds to a secondary ligand-binding site in SV2A and enhances orthosteric ligand engagement when the orthosteric site is occupied, by stabilizing the occluded state and slowing ligand dissociation. UCB1244283 shows a clear protective effect against both tonic and clonic convulsions in sound-sensitive mice. UCB1244283 can be used for epilepsy research .
Cat. No.: HY-L170
258 compounds
An emerging drug design method is based on the secondary binding site effect, where small molecule drugs are designed to bind to secondary binding sites on target biomolecules rather than primary orthomorphic sites. Successful potential drugs (known as allosteric modulators) will be able to bind to allosteric sites and remotely alter (or modify) the conformation of the main orthosteric binding sites of biological targets. Allosteric modulators (AMs) are ligands of proteins that act through binding sites different from natural (orthosteric) ligand sites. AMs are relatively small, more lipophilic, and more rigid compounds. The binding efficacy of AMs with their targets is often slightly lower. AMs are divided into positive AMs (PAMs) and negative AMs (NAMs). AMs are ideal drug targets because they can fine-tune receptor activity while preserving the spatial and temporal signal transduction characteristics of endogenous ligands, resulting in fewer targeted side effects, improved subtype selectivity, and better promotion of biased signal transduction than normal ligands.
MCE designs a unique collection of 258 small allosteric modulators. It is a good tool to be used for research on metabolize, cancer and other diseases.
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Cat. No.: HY-184268
Pim-1 kinase-IN-17 is a non-orthosteric inhibitor of PIM-1 onco-protein. Pim-1 kinase-IN-17 physically interacts with PIM-1 via a non-orthosteric binding site (Kd of 1.38 μM), does not inhibit PIM-1 kinase function, and decreases PIM-1 concentration under cellular conditions. Pim-1 kinase-IN-17 reduces tumor burden. Pim-1 kinase-IN-17 can be used for the research of triple-negative breast cancer .
Cat. No.: HY-L928
7,106 compounds
G protein-coupled receptors (GPCRs) are membrane proteins in humans and one of the most important targets in drug discovery. Approximately 35% of launched drugs are targeted GPCRs, making them a crucial class of targets in drug discovery.
The orthosteric site of a GPCR is its endogenous ligand’s (such as neurotransmitters or hormones) binding site. This site plays a central role in signal transduction. Small molecules binding to this site typically contain a protonatable amino group, enabling the formation of salt bridges or hydrogen bonds with acidic residues in the binding pocket. In contrast, the allosteric site does not directly initiate signaling but modulates the signal intensity of the GPCR by altering or stabilizing the conformation of the orthosteric site. Small molecules binding to the allosteric site often contain multiple aromatic rings to occupy hydrophobic pockets and achieve their functional effects.
MCE has collected over 7,106 reported bioactive molecules targeting GPCRs, covering Class A, B, and C GPCRs. These small molecules were subjected to AI representation to extract 2D and 3D features. Subsequently, we do screening by AI score based on similarity to identify molecules in diversity library highly similar to the reported bioactive molecules in both 2D and 3D, with a threshold greater than 0.7. Further screening based on cLogP was applied to select molecules with good lipophilicity, which facilitates the binding of small molecules to GPCRs. This diversity library can be widely applied to the discovery of compounds targeting GPCR proteins.
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Protocols
Targeted therapy! The Capetin Prize winning "Click Chemistry" can be used like this!Targeted therapy! The Nobel Prize winning "Click Chemistry" can be used like this!A suitable model is crucial in drug screening experiments. Organs can mimic the three-dimensional functional structure of internal organs, have similar spatial organization to corresponding organs, maintain some key characteristics, and reproduce some physiological functions. They are widely used for modeling and personalized drug screening physiological functions.2025-02-06
