CNX-774 is a potent, selective, and orally available small molecule inhibitor of Btk (IC50< 1 nM) that forms a ligand-directed covalent bond with Cys-481, a non-conserved amino acid within the active site of the enzyme.IC50 Value: <1 nM [1]Target: Btk KinaseIn biochemical assays, CNX-774 has demonstrated potent inhibition of Btk with an IC50 of <1nM in a continuous-read assay. The covalent bonding of CNX-774 to Btk was confirmed by incubating recombinant Btk protein with a 10-fold molar excess of CNX-774 for 1 hour at room temperature and analysis by MALDI-TOF MS. A shift of protein mass corresponding to the molecular weight of CNX-774 confirmed the covalent bonding of CNX-774 to Btk. Digestion of the covalently bonded Btk with pepsin followed by MSMS analysis established the bonding of CNX-774 to Cys-481. Cellular potency as well as prolonged duration of action of CNX-774 was demonstrated in Ramos cells by using a biotinylated covalent probe that targets the same Cysteine residue as CNX-774.CNX-774 was found to be >90% extractable after 2 hrs of incubation in both rat and human whole blood. These results demonstrate that CNX-774 has potent inhibitory activity towards the intended target, Btk, while achieving remarkable specificity in a variety of assays designed to assess off-target reactivity towards abundant cellular thiols and blood proteins.
β-Naphthoflavone-CH2-Br (β-NF-CH2-Br) is an arylhydrocarbon receptor (AhR) ligand. β-Naphthoflavone-CH2-Br can be used to synthesize the PROTAC β-NF-JQ1(HY-130256)[1].
Mant-GTPγS, a GTP mimetic, is a potent competitive adenylyl cyclase (AC) inhibitor. Mant-GTPγS is a potent YdeH inhibitor[1][2][3].
A2764 dihydrochloride is a highly selective inhibitor of TRESK (TWIK-related spinal cord K+ channel, K2P18.1), which has moderate inhibitory effects on TREK-1 and TALK-1. A2764 dihydrochloride is more sensitive to the activated mTRESK channels (IC50=6.8 μM) than the basal current. A2764 dihydrochloride can lead to cell depolarization and increased excitability in native cells, it has the potential for probing the role of TRESK channel in migraine and nociception[1].
Chlorpyrifos-oxon, an active metabolite of Chlorpyrifos, is a potent phosphorylating agent that potently inhibits AChE. Chlorpyrifos-oxon can induce cross-linking between subunits of tubulin and disrupt microtubule function[1][2][3][4].
6-Hydroxycoumarin is a coumarin which has anti-inflammatory, anti-pyretic, anti-oxidant, vasodilator, anti-amoebic, anti-bacterial, anti-fungal, bacteriostatic and antitumor activity[1].
Efipladib is a potent, selective and orally active cPLA2α inhibitor with an IC50 of 0.04 μM and a Kd of 0.067 μM[1].
b-AP15 is a specific inhibitor of the deubiquitinating enzymes UCHL5 and Usp14.
EP3 antagonist 3 (compound 2) is an orally active, potent and selective EP3 antagonist, with a pKi of 8.3. EP3 antagonist 3 shows excellent pharmacokinetic properties. EP3 antagonist 3 can be used for overactive bladder (OAB) research[1].
Dehydrocurdione, a zedoary-derived sesquiterpene, induces heme oxygenase (HO)-1, an antioxidative enzyme, in RAW 264.7 macrophages. Dehydrocurdione interacts with Keap1, resulting in Nrf2 translocation followed by activation of the HO-1 E2 enhancer. Dehydrocurdione suppresses lipopolysaccharide-induced NO release, a marker of inflammation. Anti-inflammatory activity[1][2].
Mimosine, a tyrosine analog , can act as an antioxidant by its potent iron-binding activity[1]. Mimosine is a known chelator of Fe(III)[2]. Mimosine induces apoptosis through metal ion chelation, mitochondrial activation and ROS production in human leukemic cells[3]. Anti-cancer, antiinflammation.
MM-401 is a potent inhibitor for the MLL1-WDR5 interaction with the IC50 of 0.9 nM in disrupting WDR5-MLL1 interaction. MM-401 maintains high binding affinity to WDR5 (Ki<1 nM). MM-401 specifically inhibits MLL1 H3 lysine (K) 4 methyltransferase activity but does not affect other MLL family histone methyltransferases (HMTs). MM-401 can be used for the research of MLL leukemia[1].
PI3K/mTOR Inhibitor-6 (Compound 19c) is a potent and dual inhibitor of PI3K/mTOR. PI3K/mTOR Inhibitor-6 displays better stability in artificial gastric fluids than gedatolisib. PI3K/mTOR Inhibitor-6 significantly suppresses the PI3K/Akt/mTOR signaling pathway at 10 μM. PI3K/mTOR Inhibitor-6 has the potential for the research of cancer diseases[1].
4-Fluoro-DL-glutamic acid is a glutamic acid derivative[1].
Halo PROTAC 1 is a PROTAC, which is a ligand having activity to bind to an intracellular proteins fused with HaloTag and a structure having activity to induce autophagy of an intracellular molecule are linked via a PEG linker[1].
Epristeride is a novel 5α-reductase inhibor.
Bromo-PEG2-C2-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].
Cavα2δ1&NET-IN-2 (Compound 45CS) is a dual inhibitor of the α2δ‑1 subunit of voltage-gated calcium channels (Cavα2δ-1) and the norepinephrine transporter (NET). Cavα2δ1&NET-IN-2 inhibits Cavα2δ-1 with a Ki of 454 nM. Cavα2δ1&NET-IN-2 inhibits NET with a Ki of 59 nM and IC50 of 7 nM. Cavα2δ1&NET-IN-2 can be used for research of pain[1].
6''-Acetylhyperin is a natural phenolic compounds that could be found in Nymphaea odorata[1].
Leriglitazone-d4 is deuterium labeled Leriglitazone. Leriglitazone (Hydroxypioglitazone), a metabolite of pioglitazone.Leriglitazone (Hydroxypioglitazone) PioOH is a PPARγ agonist, stabilizes the PPARγ activation function-2 (AF-2) co-activator binding surface and enhances co-activator binding, affording slightly better transcriptional efficacy.Leriglitazone (Hydroxypioglitazone) binds to the PPARγ C-terminal ligand-binding domain (LBD) with Ki of 1.2 μM，induces transcriptional efficacy of the PPARγ (LBD) with EC50 of 680 nM[1].
Ibotenic acid has agonist activity at both the N-methyl-D-aspartate (NMDA) and trans-ACPD or metabolotropic quisqualate (Qm) receptor sites.
Triamterene blocks epithelial Na+ channel (ENaC) in a voltage-dependent manner, which used as a mild diuretic.Target: Sodium ChannelTriamterene blocked rENaC in a voltage-dependent manner, and was 100-fold less potent than amiloride at pH 7.5. At -90 mV and -40 mV, the IC50 values were 5 microM and 10 microM, respectively. The blockage by triamterene, which is a weak base with a pKa of 6.2, was dependent on the extracellular pH. The IC50 was 1 microM at pH 6.5 and only 17 microM at pH 8.5 [1]. Triamterene (TA) is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active [2].
Nilotinib (AMN107) hydrochlorid is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity[1][2][3].
Ethylparaben-d4 is the deuterium labeled Ethylparaben[1].
Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of HIV.
Neuropeptide Y (29-64), amide, human is a biologically active 36-amino acid peptide.
Methyl L-pyroglutamate ((S)-Methyl 5-oxopyrrolidine-2-carboxylate;L-Pyroglutamic acid methyl ester) is isolated from P. oleracea and has anti-inflammatory activity[1].
Propan-2-amine-d6 (hydrochloride) is the deuterium labeled H-Lys-OH.2HCl[1].
Eriocalyxin B is an ent-Kaurene diterpenoid isolated from Chinese herb Isodon eriocalyx. Eriocalyxin B has anti-cancer and anti-infammatory activities. Eriocalyxin B induces cell apoptosis[1].
Protein kinase inhibitor 4 (Compound 3) is a protein kinase inhibitor that inhibits TRK-A and ROS1 (IC50=3.0 nM and 104 nM respectively)[1].