subunit-selective

Ro 25-6981 is a potent and selective activity-dependent NMDA receptors blocker containing the NR2B subunit with IC50s of 0.009 and 52 μM for cloned receptor subunit combinations NR1C/NR2B and NR1C/NR2A respectively. Ro 25-6981 can be used in studies about Parkinson's disease.

BMS 195614 (BMS614) is a selective RARα antagonist. BMS 195614 can bind to the RARα subunit.

Rp-8-CPT-cAMP is a structural combination of the lipophilic and non-hydrolyzable cAMP analogs, 8-CPT-cyclic AMP and Rp-cyclic AMPS .[1] It functions as a site-selective inhibitor of protein kinase A (PKA) type I and II, with preference towards site A of type I and site B of type II.2 By occupying cAMP binding sites at the regulatory subunit of PKA, Rp-8-CPT-cAMP prevents the kinase holoenzyme from dissociative activation.[2],[3]

Loreclezole is a selective GABAA receptor modulator and acts as a positive allosteric modulator of β2 or β3-subunit-containing receptors.

pdTp is a highly selective, small-molecule miRNA regulatory complex RISC subunit SND1 inhibitor.

CIQ is a subunit-selective potentiator of NMDA receptors containing the NR2C or NR2D subunit. EC50 value: 2.7 μM for NR2C and 2.8 μM for NR2D.

α-Conotoxin MII is a highly potent and selective competitive antagonist for α3β2 subunit-containing nicotinic receptors (IC50 = 0.5 - 3.5 nM at α3β2 expressed in Xenopus oocytes). Also potently blocks β3-containing neuronal nicotinic receptors. Displays >

Br-PBTC is a highly potent, 2/4 subtype-selective positive allosteric modulator of nicotinic acetylcholine receptors (nAChRs). It specifically targets α2β2, α2β4, α4β2, α4β4, (α4β2)2α4, and (α4β2)2β2 subtypes of nAChRs, with EC50 values ranging from 0.1 to 0.6 μM. Br-PBTC exerts its activity by binding to the c-tail region of an α subunit.

AZD-4573 is a selective and short-acting inhibitor of the serine/threonine cyclin-dependent kinase 9, the catalytic subunit of the RNA polymerase II elongation factor positive transcription elongation factor b. It also has a potential antineoplastic activ

Ipomoeassin F, a selective and potent inhibitor of endoplasmic reticulum (ER) protein translocation, targets the Sec61 complex's pore-forming subunit (Sec61α) at the ER membrane. It inhibits the ER membrane translocation of SARS-CoV-2 proteins and blocks the ER translocation of secretory and type I transmembrane proteins (TMPs), without affecting type III TMPs [1] [2] [3].

Selective antagonist of α3β4 nicotinic acetylcholine receptors. Displays > 100-fold selectivity over other receptor subunit combinations including α2β2, α2β4, α3β2, α4β2, α4β4 and α1β1γδ.

α-Conotoxin ImI is a conotoxin that has been found inC. imperialisand has receptor antagonist and anticancer activities.1It is a peptide antagonist of homomeric α7 nicotinic acetylcholine receptors (nAChRs; IC50= 220 nM). α-Conotoxin ImI is selective for α7 nAChRs over α2β2, α3β2, α4β2, α2β4, α3β4, α4β4, and α1β1γδ subunit-containing nAChRs at 5 μM but does inhibit homomeric α9 nAChRs (IC50= 1,800 nM). Administration of paclitaxel in micelles containing α-conotoxin ImI decreases tumor growth in an MCF-7 mouse xenograft model.2Intracerebroventricular, but not intraperitoneal, administration of α-conotoxin ImI (20 nmol/animal) induces seizures in rats.3 1.Johnson, D.S., Martinez, J., Elgoyhen, A.B., et al.α-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: Preferential inhibition of homomeric α7 and α9 receptorsMol. Pharmacol.48(2)194-199(1995) 2.Mei, D., Lin, Z., Fu, J., et al.The use of α-conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to α7 nAChR-overexpressing breast cancerBiomaterials4252-65(2015) 3.McIntosh, J.M., Yoshikami, D., Mahe, E., et al.A nicotinic acetylcholine receptor ligand of unique specificity, α-conotoxin ImIJ. Biol. Chem.269(24)16733-16739(1994)

Helenalin is a selective inhibitor of transcription factor NF-κB by direct targeting of p65. It is an anti-inflammatory sesquiterpene lactone compound with alkylating activity. Through its ability to target the cysteine sulfhydryl groups in the p65 subunit of NF-κB, helenalin effectively inhibits its DNA binding.

PR-924 is a selective inhibitor of tripeptide epoxyketone immunoproteasome subunit LMP-7 (IC50: 22 nM). PR-924 inhibits growth and triggers apoptosis in multiple myeloma (MM) cells. PR-924 has antitumor activities. PR-924 covalently modifies proteasomal N-terminal threonine active sites.

NFPS exerts neuroprotection via glyR alpha1 subunit in the rat model of transient focal cerebral ischaemia and reperfusion. NFPS is a selective and non-competitive glycine transporter-1 (GlyT1) inhibitor (IC50s: 2.8 nM and 9.8 nM for hGlyT1 and rGlyT1, respectively).

ONX-0914 (PR-957) TFA is a selective, noncompetitive, irreversible inhibitor targeting the chymotrypsin-like subunit (LMP7) of the immunoproteasome, effectively blocking cytokine production and mitigating the progression of experimental arthritis. With a K_i value of 5.2 μM against the mycobacterial proteasome, ONX-0914 TFA also facilitates the reactivation of latent HIV-1 by inducing p-TEFb activation through HSF-1 mediation [1] [2] [3].

Icerguastat (IFB-088) is a selective inhibitor of holophosphatase. Sephin1 safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo.

Dezapelisib is an orally bioavailable, selective inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinases (PI3K). INCB040093 prevents both the production of the second messenger phosphatidylinositol-3,4,5-trisp

σ receptor agonist and NR2B subunit-selective NMDA receptor antagonist

Thiacloprid is a neonicotinoid insecticide that acts as a selective agonist at insect nicotinic acetylcholine receptors (nAChRs) with IC50values of 2.7 and 860 nM forDrosophilanAChRs and M10 mouse fibroblast cells expressing α4β2 subunit-containing nAChRs, respectively.1It is active against aphids, whiteflies, various species of beetle, andLepidopteraspecies when used at concentrations ranging from 48 to 180 g AI/hectare.2It has anti-estrogenic activity in a yeast estrogen screen and is toxic to adult female houseflies and mice (LD50s = 0.03 and 28 mg/kg, respectively).1,3Formulations containing thiacloprid have been used in the control of insects in agriculture. 1.Tomizawa, M., and Casida, J.E.Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptorsAnnu. Rev. Entomol.48339-364(2003) 2.Elbert, A., Erdelen, C., Kuhnhold, J., et al.Thiacloprid, a novel neonicotinoid insecticide for foliar applicationProc. Brighton Crop. Prot. Conf. - Pests and Diseases121-26(2000) 3.Westlund, P., and Yargeau, V.Investigation of the presence and endocrine activities of pesticides found in wastewater effluent using yeast-based bioassaysSci. Total Environ.607-608744-751(2017)

Besonprodil is a drug that acts as an NMDA antagonist and is selective for the NR2B subunit.

UBP714 is a derivative of the NMDA receptor negative allosteric modulator UBP608. It also enhanced NMDAR mediated field EPSPs in the CA1 region of the hippocampus. UBP714 is a novel template for the development of potent and subunit selective NMDAR potent

GluN2B receptor modulator-1 is a potent and selective allosteric modulator of the GluN2B receptor. It demonstrates negative modulation, inhibiting receptor activity, and exhibits high selectivity towards the GluN2B subunit, with an impressive IC50 value of 31 nM.

DQP 1105 is a NMDA receptor antagonist.

Traxoprodil Mesylate is a potent noncompetitive N-methyl-D-aspartate (NMDA) receptors antagonist and has selective for the NR2B subunit.

NMDA receptor potentiator-1 (Compound 1368) is a subunit-selective NMDA receptor enhancer with IC50 values of 4 μM and 5 μM for NR2C and NR2D expression, respectively.

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.

Compound (S)-10a, a GluN2B subunit-selective NMDA receptor antagonist, exhibits a K i of 93 nM and an IC 50 of 72 nM. It is potentially useful for research into neurodegenerative diseases [1].

KZR-616, a first-in-class inhibitor of the immunoproteasome, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. KZR-616 has the potential for the research of multiple autoimmune diseases[1][2]. KZR-616 also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=688 nM). KZR-616 maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. KZR-616 (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1].KZR-616 is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 and PR-924 [3]. KZR-616 (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model[1]. [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem. 2018 Dec 27;61(24):11127-11143. [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685. [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646.

TCN 201 is a selective antagonist of NMDA receptors containing the NR2A subunit.

EVT-101, also known as ENS-101, is an experimental medication which originated from Roche and is under development by Evotec AG for the treatment of major depressive disorder. It acts as a selective NMDA receptor subunit 2B (NR2B) antagonist.

Ac-PAL-AMC is a fluorogenic substrate for the β1i/LMP2 subunit of the 20S immunoproteasome. Upon cleavage, 7-amino-4-methylcoumarin (AMC) is released and its fluorescence can be used to quantify the activity of the β1i/LMP2 subunit of the 20S immunoproteasome. Ac-PAL-AMC is selective for the immunoproteasome over the constitutive proteasome. AMC displays excitation/emission maxima of 351/430 nm, respectively.

UBP 302 is an effective and selective GLUK5-subunit-containing kainate receptor antagonist (apparent Kd=402 nM) and displays very little affinity on GluK2 kainate receptors.

TC-1698 dihydrochloride is a selective nicotinic α7 receptor agonist that also displays weak partial agonist/antagonist activity at β-subunit-containing receptors. This product is a neuroprotectant.

VU0466551 is a selective activator of homomeric G protein gated, inwardly rectifying, potassium subunit 1 (GIRK1) channels.

Etrolizumab (rhuMAb Beta7), a gut-selective anti-β7 integrin monoclonal antibody, targets the β7 subunit of α4β7 and αEβ7 integrins specifically, demonstrating affinity with K i values of 18 nM for Human α4β7 and 1800 pM for Human αEβ7-293. It is utilized in the research of inflammatory bowel disease (IBD) [1] [2].

Ro 25-6981 Maleate is a selective NR2B subunit-specific NMDA receptor antagonist with anticonvulsant and antidepressant activity, which can be used in the study of neurological disorders such as Parkinson's and epilepsy.

Thymidine 3',5'-diphosphate tetrasodium (Deoxythymidine 3′,5′-diphosphate tetrasodium) acts as a selective inhibitor targeting staphylococcal nuclease, tudor domain-containing 1 (SND1, a MicroRNA regulatory complex RISC subunit), and [3,5-2H2] tyrosyl nuclease. It possesses anti-tumor properties and serves as a catalyst in various biochemical reactions [1] [2].

Rpn11-IN-1 is an effective and selective inhibitor of proteasome subunit Rpn11 (IC50: 390 nM).

Sephin1 (IFB-088) is reportedly a selective inhibitor of GADD34 (PPP1R15A), which is a stress-induced regulatory subunit of protein phosphatase 1 complex that dephosphorylates eIF2α

PKA-IN-1 is a selective and potent cyclic AMP-dependent protein kinase (PKA) catalytic subunit (cAK) inhibitor (IC50: 0.03 μM).PKA-IN-1 can be used to study diseases of the immune system.

NS11394 is a effective and subtype-selective GABA(A) receptor-positive modulator; possesses a functional efficacy selectivity profile of α(5) > α(3) > α(2) > α(1) at GABA(A) alpha subunit-containing receptors.

ZK93423 is a potent agonist of benzodiazepine receptor (IC50 = 1 nM) with non-selective between α1-, α2-, α3- and α5-subunit containing GABAA receptors, Ki values are 4.1, 4.2, 6 and 4.5 nM for inhibition of [3H]Ro15-1788 binding to human recombinant α1β3

Phosphatidylinositol 3-kinase (PI3K) catalyzes the phosphorylation of the 3' hydroxyl position of PIs to produce the second messengers PtdIns-(3,4)-P2 and PtdIns-(3,4,5)-P3. PI3Kα, β, and δ are class 1A enzymes composed of p110 and p85 subunits, whereas PI3Kγ is a class 1B PI3K composed of a p110 catalytic subunit and a p101 or p84 regulatory subunit. PI3Kα inhibitor 2 is a selective inhibitor of PI3Kα with IC50 values of 2, 16, 660, and 220 nM for the α, β, γ, and 2Cβ isoforms, respectively. It inhibits PKA, KDR, PKCα, and cyclin E/Cdk2 significantly less effectively (IC50 = 91, 3.4, 466, and 28 μM, respectively). PI3Kα inhibitor 2 inhibits A375 melanoma cell proliferation with an IC50 value of 580 nM.

ILS-920 is a Rapamycin analog characterized by diminished immunosuppressive effects but remarkable neuroprotective properties. It exhibits selective binding affinity towards the immunophilin FKBP52 as well as the β1-subunit of L-type voltage-gated calcium channels (VGCC). ILS-920 displays a notable 200-fold preference for FKBP52 over FKBP12.

Ro 25-6981 HCl is an effective and selective NMDA glutamate receptors containing the NR2B subunit antagonist.

Sephin1 hydrochloride is a selective inhibitor of the phosphatase regulatory subunit PPP1R15A (R15A), which prolongs the benefit of eIF2α phosphorylation, thereby protecting cells from proteostatic defects.