at-56

AT56, a specific inhibitor of prostaglandin D2 synthase enzymatic activity, blunted adipogenic aldosterone effects.

GAT564 (Compound 15d) is a highly effective allosteric modulator of the cannabinoid 1 receptor (CB1R), with EC50 values of 87 nM for cAMP and 320 nM for β-arrestin2. It significantly enhances the binding of orthosteric ligands to hCB1R and exhibits remarkable efficacy as a topical agent, significantly reducing intraocular pressure (IOP) in an ocular normotensive murine model of glaucoma [1].

Org 25543 hydrochloride is a potent and selective glycine transporter type 2 (GlyT2) inhibitor (IC50 = 16 nM for hGlyT2). Displays no activity at GlyT1 or 56 other common biological targets (≥ 100 μM), in a glycine uptake assay in CHO cells.

Unifiram is a nootropic agent.1It increases acetylcholine (ACh) release in the rat cerebral cortexin vivoand induces a long-lasting increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) in the rat hippocampal CA1 region (EC50= 27 nM). It does not bind to serotonin (5-HT), dopamine, muscarinic, nicotinic, adrenergic, glutamate, histamine, opioid, or GABA receptors at 1 μM. Unifiram (0.1 mg/kg) improves memory in non-memory-impaired rats in a social learning test.2It also prevents memory deficits induced by the anticholinergic agent scopolamine, nicotinic receptor antagonist mecamylamine, GABABreceptor agonist baclofen, or α2-adrenergic receptor agonist clonidine in the passive avoidance test in mice when administered at a dose of 0.01 mg/kg and prevents memory deficits induced by the AMPA/kainate glutamate receptor antagonist NBQX at 0.1 mg/kg.1 1.Romanelli, M.N., Galeotti, N., Ghelardini, C., et al.Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancersCNS Drug Rev.12(1)39-52(2006) 2.Ghelardini, C., Galeotti, N., Gualtieri, F., et al.The novel nootropic compound DM232 (unifiram) ameliorates memory impairment in mice and ratsDrug Develop. Res.56(1)23-32(2002)

CYM50308 is a high affinity agonist of sphingosine-1-phosphate receptor 4 (S1P4-R) (EC50: 56 nM). CYM50308 has no activity at S1P1-R, S1P2-R and S1P3-R subtypes at concentrations up to 25 μM and it shows 37-fold more selective for S1P4-R than S1P5-R.

PROTAC CDK9 degrader-11 (Compound C3) is an orally active PROTAC CDK9 degrader with a DC50 of 1.09 nM. This compound exhibits cytotoxicity in small cell lung cancer (SCLC) cells, with IC50 values in the nanomolar range. It induces cell cycle arrest at the G0/G1 phase and inhibits cell invasion in DMS114 and DMS53 cells. In addition, PROTAC CDK9 degrader-11 shows antitumor activity in an NCI-H446 xenograft mouse model. (Pink: ligand for target protein CDK9 ligand 3; Black: linker; Blue: ligand for E3 ligase Cereblon E3 ligase Ligand 56)

YW3-56 is a potent peptidylarginine deiminase (PAD) inhibitor, with an IC50 of 1-5 μM for PAD4. Compared with Cl-amidine, YW3-56 shows >60-fold increase in cell growth inhibition efficacy (IC50 about 2.5 μM) but only 5-fold increase in PAD4 inhibition (IC sub>50 about 1-5 μM). At 2-4 μM concentrations, YW3-56 displays mainly cytostatic effects by slowing cell division, whereas at higher concentrations, it exerts cytotoxic effects by altering cell morphology and killing cells[1]. [1]. Wang Y, et al. Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and t he mammalian target of rapamycin complex 1 activity. J Biol Chem. 2012 Jul 27;287(31):25941-53.

11β-PGE2 is the C-11 epimer of PGE2. It is a moderate inhibitor of PGE2 binding to rat hypothalamic membranes with a Ki value of 53 nM.[1] 11β-PGE2 also stimulates bone resorption in rats at concentrations of 10-8 to 10-6 M which is similar to PGE2.2 11β-PGE2 inhibits PGE2 binding to the prostaglandin transporter protein with a Ki of 56 nM.[3] .

AN3661, a potent antimalarial lead compound, targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue subunit 3 (PfCPSF3) and inhibits Plasmodium falciparum laboratory-adapted strains, Ugandan field isolates, and murine P. berghei and P. falciparum infections[1].

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide (T0267) is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg/ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg/ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide (T0267) inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg/kg, respectively). Zonisamide (T0267) (40 mg/kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy.

Purfalcamine is an orally active, selective Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) inhibitor with an IC50 of 17 nM and an EC50 of 230 nM, exhibiting antimalarial activity by inducing developmental arrest of malaria parasites at the schizont stage[1][2].

Cambinol (SIRT1/2 Inhibitor IV) is a cell-permeable b-naphthol compound that inhibits the NAD-dependent deacetylase activity of SIRT1/2 (IC50: 56/59 μM, respectively) in a substrate-, but not NAD-, competitive manner. Cambinol inhibits SIRT5 deacetylase activity only at much higher concentrations (IC50 >300 μM) and no inhibitory for the class I and II HDACs. In BCL6-expressing Burkitt lymphoma cell lines, Cambinol-induced apoptosis has been attributed to the hyperacetylation of p53 and BCL6.Cambinol is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor)

Anticancer agent 56 (compound 4d) is a powerful anti-cancer compound with favorable drug-like properties, showing significant anticancer activity against multiple cancer cell lines with an IC50 value of less than 3 μM. It exerts its effects by causing cell cycle arrest at the G2/M phase and activating the mitochondrial apoptosis pathway, inducing the accumulation of reactive oxygen species (ROS), upregulating BAX, downregulating Bcl-2, and triggering the activation of caspases 3, 7, and 9 [1].

Tofacitinib maleate, also known as tasocitinib, CP-690550, is a Janus kinase (JAK) inhibitor. Tofacitinib maleate modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. JAK enzymes transmit cytokine signaling through pairing of JAKs (e.g., JAK1/JAK3, JAK1/JAK2, JAK1/TyK2, JAK2/JAK2). Tofacitinib maleate inhibited the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC50 of 406, 56, and 1377 nM, respectively.

Tofacitinib HCl, also known as tasocitinib, CP-690550, is a Janus kinase (JAK) inhibitor. Tofacitinib HCl modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. JAK enzymes transmit cytokine signaling through pairing of JAKs (e.g., JAK1/JAK3, JAK1/JAK2, JAK1/TyK2, JAK2/JAK2). Tofacitinib HCl inhibited the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC50 of 406, 56, and 1377 nM, respectively.

PD-85639 is a voltage-gated sodium (Na+) channel blocker (75% in 10 min & >95% in 25 min blockage of Na+ current by 25 μM PD85,639; whole-cell patch clamp using primary rat brain neurons) that is shown to target rat brain Nav1.2 with simultaneous high- and low-affinity modes of binding (EC50 = 56 nM/40% & 20 μM/60% at pH 9.0, 5 nM/28% & 3 μM/72% at pH 7.4, against 2 nM [3H]-PD85,639 for binding rat brain synaptosomes; EC50 = 17 nM/39% & 10 μM/61% using at pH 9.0 using rat brain synaptosome membranes) and a fast kinetic (t1/2 = 1.2 at 4°C, <0.5 min at 25°C), competitive against the local anesthetic Na+ channel blockers tetracaine, bupivacaine, and mepivacaine, as well as Na+ channel activators veratridine and batrachotoxin (K1 = 0.26 μM against 5 nM [3H]-BTX for binding rat neocrotical membranes).

3-Acetyl-6-bromocoumarin is a coumarin derivative exhibiting potent antioxidant activity, demonstrated at a rate of 56% [1].

Klotho-derived Peptide 1 (56-87) (human) TFA, a peptide derived from the human Klotho protein, disrupts TGF-β signaling through binding interactions with TGF-β receptor type 1 (TGFBR1) and TGF-β receptor type 2 (TGFBR2), with Kd values of 1.41 and 14.6 µM, respectively. Preincubation with Klotho-derived Peptide 1 (56-87) (human) TFA at 10 µg/mL inhibits TGF-β-induced increases in fibronectin and α-smooth muscle actin (α-SMA) expression in NRK-49F rat fibroblasts. In vivo investigations demonstrate that Klotho-derived Peptide 1 (56-87) (human) TFA, administered at 1 mg/kg per day, preferentially accumulates in damaged kidneys and significantly reduces serum creatinine and blood urea nitrogen levels while decreasing renal fibrosis in mouse models of unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury-induced renal fibrosis. Klotho-derived Peptide 1 (56-87) (human) TFA is therefore valuable for investigations involving renal fibrosis, TGF-β signaling modulation, and kidney injury-associated molecular pathways.

Poloxamer 122 L42 is a block copolymer of polyethylene oxide and polypropylene oxide, with an average molecular weight of 1630. It exhibits antibacterial activity, inhibiting 56% of Mycobacterium avium at a concentration of 1 mg/mL. Poloxamer 122 L42 can form thermoreversible hydrogels and is employed as a food additive, and serves as a drug delivery carrier in cosmetics, pharmaceuticals, and tissue engineering.