Cabotegravir is a potent HIV integrase inhibitor as an oral lead-in tablet and long-acting injectable for the treatment and prevention of HIV infection. Cabotegravir is an inhibitor of OAT1 (IC50 0.81 μM) and OAT3 (IC50 0.41 μM).IC50 value: 0.81 μM (OAT1), 0.41 μM (OAT3) [1]Target: OAT1, OAT3Cabotegravir is a potent HIV integrase inhibitor in clinical development as an oral lead-in tablet and long-acting injectable for the treatment and prevention of HIV infection.[2] Cabotegravir is an HIV-1 integrase inhibitor under development as a tablet for both oral lead-in therapy and long-acting (LA) injectable for intramuscular dosing.[3]
12-Hydroxy-2,3-dihydroeuparin (compound 7) is a natural product that can be isolated from the aerial parts of Ophryosporus axilliflorus. 12-Hydroxy-2,3-dihydroeuparin shows extremely anti-inflammatory activity[1].
Pimethixene maleate is antihistamine and antiserotonergic compound, acts as an antimigraine agent.Pimethixene maleate is a highly potent antagonist of 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, histamine H1, dopamine D2 and D4.4 as well as muscarinic M1 and M2 receptors, with pKis of 7.63, 10.22, 10.44, 8.42, 10.14, 8.19, 7.54, 8.61 and 9.38, respectively[1].
Cardamonin (Cardamomin), a natural flavone isolated from Alpinia katsumadai Hayata, acts as an aryl hydrocarbon receptor (AhR) activator. Cardamonin alleviates inflammatory bowel disease by the inhibition of NLRP3 inflammasome activation via an AhR/Nrf2/NQO1 pathway[1].
Flunisolide is a corticosteroid often used to treat allergic rhinitis.The principal mechanism of action of Flunisolide is to activate glucocorticoid receptors, meaning it has an anti-inflammatory action.
Boc-Aminooxy-PEG3-bromide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].
A 419259 is a broad-spectrum pyrrolo-pyrimidine inhibitor, designed to enhance selectivity towards the Src family with IC50 of 9 nM, <3 nM and <3 nM for Src, Lck and Lyn, respectively.
Akt1&PKA-IN-1 is a potent dual Akt/PKA inhibitor with IC50 values of 0.03 , 0.11 μM, and 9.8 μM for PKAa, Akt, and CDK2, respectively. Akt1&PKA-IN-1 is selective for cyclin-dependent kinase 2 (CDK2)[1].
[MePhe7]-Neurokinin B is an neurokinin NK-3 receptor (NK3R) agonist with an IC50 value of 3 nM. [MePhe7]-Neurokinin B is a potential regulator of pulsatile gonadotropin-releasing hormone (GnRH) secretion via activation of the neurokinin-3 receptor (NK3R)[1].
OYYF-175, an antimicrobial antifolate, is a dihydrofolate reductase (DHFR) inhibitor with an IC50 of 2.36 nM for Escherichia coli DHFR. OYYF-175 exhibits potent broad-
GW433908 is a phosphate ester prodrug of the antiretroviral protease inhibitor amprenavir, with improved solubility over the parent molecule and a potential for reduced pill burden on current dosing regimens; GW433908G is the calcium salt of the prodrug.IC50 Value:Target: HIV Proteasein vitro: There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine[1].in vivo: Fosamprenavir-ritonavir administered with methadone did not alter plasma amprenavir pharmacokinetics compared with historical control data; nor did it alter the unbound R-methadone at 2 and 6 hours after methadone dosing. Pharmacodynamic indexes remained essentially unchanged after adding fosamprenavir-ritonavir to methadone [2]. After a high-fat meal compared with fasting, (1) the bioavailability of GW433908G suspension was decreased by 20% and Cmax by 41%, and (2) for GW433908G tablets, there was no influence on AUC(12% lower Cmax). After a low-fat meal compared with fasting, (1) there was bioequivalence for GW433908G tablets, but (2) bioavailability was decreased by 23% for amprenavir capsules (Cmax was also lower, by 46%) [3].Clinical trial: Study of an Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects. Phase 2
2-Amino-1-β-D-arabinofuranosyl-5-methyl-4(1H)-pyrimidinone is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].
Mal-Ala-Ala-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].
Gomisin E, a dibenzocyclooctadiene lignan isolated from the fruits of Schizandra chinensis, inhibits NFAT transcription with an IC50 of 4.73 μM[1][2].
Birinapant, a bivalent Smac mimetic, is a potent antagonist for XIAP and cIAP1 with Kds of 45 nM and less than 1 nM, respectively.
(-)-β-Peltatin is an organic heterotetracyclic compound with antitumor activity and phytometabolite effects that are functionally related to α-peltatin[1].
DSLET ([D-Ser2, Leu5, Thr6]-enkephalin) is a highly specific agonist of the δ-receptor. DSLET is an enkephalin-related peptide selectively bound to the δ opioid receptor[1][2].
Metolazone-d7 is deuterium labeled Metolazone. Metolazone (SR-720-22) is primarily used to treat congestive heart failure and high blood pressure.
Benzyl selenocyanate is a chemopreventive agent for various chemically induced tumors in animal models at both the initiation and postinitiation stages. Benzyl selenocyanate is an inhibitor of DNA (cytosine-5)-methyltransferase (Mtase), with an with an IC50 of 8.4 µM[1].
Fmoc-D-Ser(tBu)-OH is a serine derivative[1].
M77976 is a specific ATP-competitive inhibitor of PDK4 (pyruvate dehydrogenase kinase isoforms 4), with an IC50 of 648 μM. M77976 is potential for the research of obesity and diabetes[1].
Octopamine Hydrochloride is an endogenous biogenic amine that is closely related to norepinephrine, and has effects on the adrenergic and dopaminergic systems.Target: Dopamine Receptor; Adrenergic ReceptorOctopamine is present in relatively high concentrations in neuronal as well as in non-neuronal tissues of most invertebrate species studied, and modulates almost every physiological process. Octopamine acts as neurohormone including desensitization of sensory inputs, influence on learning and memory, or regulation of the mood of the animal in the central nervous system. Octopamine is the only neuroactive non-peptide transmitter whose physiological role is restricted to invertebrates, and all octopamine receptors belong to the family of G-protein coupled receptors [1].Octopamine (10 μM) injected into the mushroom body (MB) calyces or the antennal lobe but not the lateral protocerebral lobe produces a lasting, pairing-specific enhancement of extension of the proboscis. Octopamine (10 μM) injected into the MB calyces results in an additional pairing-specific effect, because it does not lead to an acquisition but a consolidation after conditioning [2]. Octopamine treatment significantly elevates levels of octopamine in the brain and caused a significant dose-dependent increase in the number of new foragers. Octopamine treatment is effective only when given to bees old enough to forage, i.e., older than 4 days of age. Octopamine influences division of labor in honey bee colonies [3].
Bik BH3 is a biological active peptide. (BH3 domain of BIK)
Amgen-23 (compound 23) is a potent sphingosine kinases (SPHK) inhibitor with IC50 values of 20 nM and 1.6 μM for SPHK1 and SPHK2, respectively. Amgen-23 can be used for researching anticancer[1].
Atazanavir-d6 is deuterium labeled Atazanavir. Atazanavir (BMS-232632), a highly selective HIV-1 protease inhibitor, is the first protease inhibitor approved for once-daily administration[1]. Atazanavir (BMS-232632) is a substrate and inhibitor of CYP3A4, and an inhibitor and inducer of P-glycoprotein (P-gp)[2]. Atazanavir is also a SARS-CoV 3CLpro inhibitor with an IC50 of 3.49 μM[3].
Ro 24-4736 is a potent, selective, p.o.-active platelet-activating factor (PAF) antagonist with a long duration of action.
TAK-632 is a potent pan-RAF inhibitor with IC50 of 1.4, 2.4 and 8.3 nM for CRAF, BRAFV600E, BRAFWT, respectively.
RGD-4C is a arginine-glycine-aspartic acid peptide (ACDCRGDCFC) with integrin binding activity. The Arg-Gly-Asp (RGD) sequence serves as the primary integrin recognition site in extracellular matrix proteins, and peptides containing this sequence can mimic the recognition specificity of the matrix proteins. RGD-4C is a αv-integrin ligand, can conjugate with bioactive molecule to exert antitumor effects in animal models[1][2][3].
Eltoprazine(DU28853) is a serenic or antiaggressive agent which as an agonist at the 5-HT1A and 5-HT1B receptors and as an antagonist at the 5-HT2C receptor.IC50 value:Target: 5-HT1A/1B agonist; 5-HT2C antagonistin vitro: The binding of [3H]eltoprazine to whole tissue sections was saturable and revealed an apparent dissociation constant (Kd) of 11 nM. Specific [3H]eltoprazine binding was completely displaced by 5-HT; conversely, unlabelled eltoprazine reduced [3H]5-HT binding to the levels of non-specific binding [1]. Eltoprazine evoked membrane changes that were similar to but much weaker than those induced by 5HT. Both the 5HT- and eltoprazine-evoked membrane hyperpolarizations were largely suppressed in the presence of spiperone [2].in vivo: eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models [3]. Rats were chronically treated with mianserin (10 mg/kg i.p.) or eltoprazine (1 mg/kg i.p.) and were tested in the elevated plus-maze test for anxiety. Mianserin and eltoprazine displayed opposite effects in the elevated plus-maze: mianserin induced anxiolytic-like effects, while eltoprazine showed anxiogenic-like ones [4].
Ac-KQKLR-AMC (Cathepsin S substrate) is a biological active peptide. (Cathepsins are a class of globular lysosomal proteases, playing a vital role in mammalian cellular turnover. They degrade polypeptides and are distinguished by their substrate specificities. Cathepsin S is a cysteine proteinase involved in the pathogenesis of autoimmune diseases, atherosclerosis, cancer, obesity and related diseases.This peptide is a cathepsin S substrate fluorescently labeled with AMC (Ex/Em=354 nm/442 nm). It can be used to measure cathepsin S activity.)