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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
621 Results for "
Allosteric modulators
" in MedChemExpress (MCE) Product Catalog:
Products (621)
621 Results for "Allosteric modulators" in MCE Product Catalog:
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TRPC6-PAM-C20 is a selective positive allosteric modulator (PAM) of TRPC6 channels. TRPC6-PAM-C20 is a potent enhancer of channel activation, enabling low basal concentrations of DAG to induce activation of the ion channel. TRPC6-PAM-C20 induces increases in intracellular Ca 2+ concentrations ([Ca 2+]i) in TRPC6-expressing HEK293 cells with an EC50 of 2.37 μM. TRPC6-PAM-C20 can be used as a valuable tool to selectively exaggerate TRPC6-dependent signals .
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DQP-997-74 (compound 2i) is a selective negative allosteric modulator of N-methyl-d-aspartate receptor (NMDAR), specifically targeting GluN2C/D (IC50: 0.069 μM and 0.035 μM), with blood-brain barrier penetrability. Where DQP refers to dihydroquinoline-pyrazoline. DQP-997-74 acts synergistically with the agonist glutamate to exhibit time-dependent enhanced potency in inhibiting hypersynchronous activity driven by high-frequency excitatory synaptic transmission. DQP-997-74 reduces the number of epileptogenesis in a murine model of tuberous sclerosis complex (TSC)-induced epilepsy. DQP-997-74 can be used for research on NMDAR-related neurological diseases .
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Delta3,5-cholestadien-7-one is an oxysterol and a negative allosteric modulator of GABAA receptors. Delta3,5-cholestadien-7-one reduces GABA-induced currents in HEK cells expressing α1β1γ2 or α4β3γ2 subunit-containing GABAA receptors with IC50 values of 1.5 and 1 µM, respectively. Delta3,5-cholestadien-7-one reduces GABA-induced depolarization of peptidergic and non-peptidergic nociceptors, C-LTMRs, and cold thermosensors in isolated mouse dorsal root ganglion (DRG) neurons .
Cat. No.: HY-175505
CAS No.: 2894793-37-2
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Dopamine D3 receptor antagonist-3 is a D3 dopamine receptor (D3R)-selective positive allosteric modulator (PAM)-antagonist that can cross the blood-brain barrier. Dopamine D3 receptor antagonist-3 exhibits antagonist activity in the D3R-mediated β-arrestin recruitment assay with an IC50 and a Kd of 2.5 μM and 0.49 μM. amine D3 receptor antagonist-3 is also an antagonist in the D3R-mediated Go-BRET assay with an IC50 of 0.34 μM. Dopamine D3 receptor antagonist-3 can be used for the study of neuropsychiatric disorders, including substance use disorder .
Cat. No.: HY-180400
CAS No.: 1426293-61-9
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PAM-2 is a potent, orally active, CNS-penetrant selective α7 nAChR positive allosteric modulator (human α7 nAChR EC50: 39 μM, rat α7 nAChR EC50: 12 μM) with anti-nociceptive and anti-inflammatory activity. PAM-2 exhibits selectivity over α9α10 nAChR (IC50 = 174 μM) and CaV2.2 channel (IC50 = 89 μM). PAM-2 decreases Streptozotocin (STZ) (HY-13753)- and Oxaliplatin (HY-17371)-inducned nuroparhic pain in mice by α7 nAChR potentiation. PAM-2 can be used for the research of neuropathic pain .
Cat. No.: HY-19888
CAS No.: 1001389-72-5
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GSK-1482160 is an orally active and blood-brain barrier penetrant P2X7 receptor (P2X7R) negative allosteric modulator with pIC50s of 8.5 (human) and 6.5 (rat). GSK-1482160 reduces the efficacy of ATP at the P2X7 receptor without affecting its affinity, thereby inhibiting the release of IL-1β. GSK-1482160 is an effective radioligand and can be labeled with radioactive isotopes like 11C or 18F to image P2X7R. GSK-1482160 can be used for the studies of chronic joint pain and chronic constriction injury (CCI) .
Cat. No.: HY-L943
37030 compounds
MCE-18 stands for Medicinal Chemistry Evolution 2018, which was first published in Journal of Medicinal Chemistry in 2019 for assessing molecular novelty and three-dimensional complexity. Developed based on Clarivate global pharmaceutical patent database, this descriptor was constructed via big-data analysis covering 28,161 patented lead compounds, 1,370 approved drugs and nearly 30,000 preclinical-to-phase III drug candidates from 23 top pharmaceutical companies worldwide between 1950 and 2018, followed by structural clustering and removal of redundant outdated scaffolds for data denoising. Its scoring system integrates five core structural features including aromatic ring (AR), aliphatic heterocycle (NAR), chiral center (CHIRAL), spiro atom (SPIRO), cyclic and acyclic sp³ carbon ratio together with a quadratic topological correction factor. Breaking the limitations of the single Fsp³ parameter, MCE-18 effectively distinguishes conventional flat aromatic scaffolds from modern 3D-enriched novel chemotypes, overcoming typical drawbacks of traditional compound libraries such as scaffold redundancy, low screening hit rates and poor compatibility with allosteric and PPI-related difficult targets.
This library contains over 37,000 structurally diverse compounds with favorable overall drug-likeness, suitable for high-throughput screening against canonical targets including kinases, GPCRs and proteases as well as challenging allosteric and PPI targets. Compounds comply with the developmental trend of modern novel drug discovery, supporting routine primary screening as well as early hit identification of allosteric modulators and PPI inhibitors, serving as an efficient screening resource for early-stage innovative drug discovery.
Cat. No.: HY-107111R
CAS No.: 932373-87-0
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GSK1034702 (Standard) is the analytical standard of GSK1034702 (HY-107111). This product is intended for research and analytical applications. GSK1034702 is an orally active and allosteric agonist of M1 mAChR (pEC50=8.1) that can cross the blood-brain barrier. GSK1034702 activates the Gq/11 protein-mediated signaling pathway, enhancing neuronal firing and long-term potentiation (LTP) in the CA1 region of the hippocampus. GSK1034702 can modulate hippocampal function, improve memory encoding in the nicotine withdrawal cognitive dysfunction model, and show pro-cognitive effects in rodents. GSK1034702 can be used for the study of the mechanisms of cognitive impairment diseases such as Alzheimer's disease, and has certain peripheral M receptor activation-related side effects (such as gastrointestinal reactions) .
Cat. No.: HY-117106
CAS No.: 200266-76-8
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PNU-107484A is a GABAA receptor ligand that exhibits target activity mechanisms dependent on α isoforms. In the α1β2γ2 subtype, PNU-107484A acts as a positive allosteric modulator, enhancing GABA-induced Cl - currents, while it inhibits the currents in the α3β2γ2 and α6β2γ2 subtypes. The half-maximal concentrations for the α1β2γ2, α3β2γ2, and α6β2γ2 subtypes are 3.1, 4.2, and 3.5 μM, respectively. PNU-107484A can be used as a probe to investigate the physiological roles of different α isoform subtypes .
Synonyms: PF-06372865; CVL-865
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Darigabat (PF-06372865) is an orally active, α2/α3/α5 subtype-selective GABAA positive allosteric modulator (PAM). Darigabat is a high affinity ligand at GABAA receptors containing α1/α2/α3/α5 subunits (Kis of 2.9 nM, 21 nM, 134 nM for α2, α1 PAM, α2 PAM, respectively), with low affinity for α4/α6 subunits. Darigabat can across the blood-brain barrier (BBB). Darigabat has anxiolytic activity and has the potential for epilepsy .
Cat. No.: HY-123382
CAS No.: 1695551-19-9
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GSK-1482160 isomer is the isomer of GSK-1482160 (HY-19888). GSK-1482160 is an orally active and blood-brain barrier penetrant P2X7 receptor (P2X7R) negative allosteric modulator with pIC50s of 8.5 (human) and 6.5 (rat). GSK-1482160 reduces the efficacy of ATP at the P2X7 receptor without affecting its affinity, thereby inhibiting the release of IL-1β. GSK-1482160 is an effective radioligand and can be labeled with radioactive isotopes like 11C or 18F to image P2X7R. GSK-1482160 can be used for the studies of chronic joint pain and chronic constriction injury (CCI).
Cat. No.: HY-131997
CAS No.: 89112-85-6
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2'MeO6MF is a brain-penetrant positive allosteric modulator at α2β1γ2L and all α1-containing GABAA receptors. 2'MeO6MF also can directly activate α2β2/3 and α2β2/3γ2L GABAA receptors. 2'MeO6MF has anxiolytic and psychomotor stabilizing properties. 2'MeO6MF offers neuroprotection and improved functional recovery and dampens the stroke-induced inflammatory response .
Cat. No.: HY-15446R
CAS No.: 802906-73-6
Synonyms: RG7090 (Standard); RO4917523 (Standard)
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Basimglurant (RG7090; RO4917523) (Standard) is the analytical standard of Basimglurant. This product is intended for research and analytical applications. Basimglurant is a selective, orally active, blood-brain barrier permeable negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), with a Ki of 1.4 nM (against [ 3H]-ABP688 (HY-110141)) and 35.6 nM (against [ 3H]-MPEP (HY-14609A)). Basimglurant inhibits mGlu5-mediated signaling pathways and receptor constitutive activity, regulates dopamine levels in the nucleus accumbens, exerts anxiolytic, antidepressant-like, analgesic and arousal-promoting effects, and alters δ-wave power during non-rapid eye movement sleep. Basimglurant can be used in research on depression, fragile X syndrome, anxiety disorders, etc.
Cat. No.: HY-175504
CAS No.: 932544-59-7
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MLS6357 is a D3 dopamine receptor (D3R)-selective positive allosteric modulator (PAM)-antagonist. MLS6357 exhibits antagonist activity in the D3R-mediated and the BRET-based β-arrestin recruitment assay with IC50s of 13 and 14 μM, and no activity for other DAR subtypes (D1R/D2R/D4R/D5R) (IC50 > 100 μM). MLS6357 is also an antagonist in the D3R-mediated Go-BRET assay with an IC50 of 17 μM. MLS6357 can be used for the study of neuropsychiatric disorders, including substance use disorder .
Cat. No.: HY-181102
CAS No.: 3081614-92-5
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TGR5 agonist 10 is a selective, allosteric and orally active Takeda G protein coupled receptor 5 (TGR5) agonist with EC50s of 0.8 μM and 0.6 μM for human TGR5 and mouse TGR5, respectively. TGR5 agonist 10 demonstrates selectivity for TGR5 over FXR. TGR5 agonist 10 activates hTGR5 and mTGR5 to induce cAMP accumulation, and positively modulates lithocholic acid functional activity and potency at hTGR5, with higher selectivity for cAMP formation over β-arrestin2 recruitment. TGR5 agonist 10 exerts glucose-lowering effects in Mus musculus oral glucose tolerance tests. TGR5 agonist 10 can be used for the research of diabetes .
Cat. No.: HY-185978
CAS No.: 2133456-91-2
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GL-II-73 is a selective, orally active and blood-brain barrier permeable positive allosteric modulator of α5GABAA receptor, acting on the benzodiazepine-binding site of GABAA receptors. The binding selectivity of GL-II-73 for the α5 subtype is 6-, 11- and 12.5-fold higher than that for the α2, α1 and α3 subtypes, respectively . GL-II-73 reverses pilocarpine-induced hyperactivation of dopamine neurons in the ventral tegmental area, improves working memory and pyramidal neuron dendritic morphology in 5xFAD mice, but does not reduce β-amyloid load . GL-II-73 can be used in research related to Alzheimer's disease and temporal lobe epilepsy with comorbid psychosis .
Cat. No.: HY-182707
CAS No.: 2055045-42-4
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JWX-A0108 is a selective human α7 nAChR positive allosteric modulator with an EC50 of 4.35 μM. JWX-A0108 potentiates α7 nAChR currents only in the presence of acetylcholine, with no direct activating effect or alteration of desensitization. JWX-A0108 enhances hippocampal GABAergic synaptic transmission by increasing spontaneous inhibitory postsynaptic currents. JWX-A0108 reduces the brain expression levels of IL-1β, TNF-α, and IL-6 by blocking the NF-κB signaling pathway, and reduces microglial activation by downregulating Iba1. JWX-A0108 effectively improves cognitive deficits, neuroinflammation, and hippocampal neuronal damage in mouse models of schizophrenia and Alzheimer's disease. JWX-A0108 can be used for research related to schizophrenia and Alzheimer's disease .
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.
Synonyms: RG-7816; RO-7017773
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Alogabat is a positive allosteric modulator (PAM) and agonist (Ki <100 nM) of the GABAA α5 receptor, targeting the α5β3γ2 subunit with a Ki of 8.7 nM. Alogabat increases the expression level of α5β3γ2 in oocytes (1.97-fold). GABAA has been implicated in cognitive impairment associated with central nervous system (CNS) disorders, brain cancer (including brain tumors such as medulloblastoma), and can be used in the study of mild cognitive impairment (MCI), amnestic MCI (aMCI), age-associated memory impairment (AAMI), age-related cognitive decline (ARCD), dementia, Alzheimer's disease (AD), prodromal AD, post-traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cognitive impairment associated with cancer treatment, mental retardation, Parkinson's disease (PD), autism spectrum disorder, fragile X, Rett syndrome, obsessive-compulsive behavior, and substance addiction .
Cat. No.: HY-187088
CAS No.: 1198309-73-7
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AZD-8418 is an orally active positive allosteric modulator of metabotropic glutamate receptor 2 (mGluR2), with an EC50 of 0.86 μM for rat mGlu2 receptors. AZD-8418 reduces the in vitro binding level of [ 3H]AZ12559322 in prefrontal cortex brain tissues of non-human primates. AZD8418 enhances the inhibitory effect of the mGlu2/3 agonist DCG-IV (HY-101335) on field excitatory postsynaptic potentials (fEPSP) in rat hippocampal brain slices. AZD-8418 reduces nicotine self-administration behavior in rats, and blocks cue-induced reinstatement of nicotine-seeking and food-seeking behaviors. The attenuating effect on nicotine self-administration behavior develops rapid tolerance, while inhibition of food self-administration behavior requires chronic administration. AZD-8418 can be used in research related to nicotine dependence and neuropsychiatric disorders .
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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
