t-200

4’-hydroxy Trazodone is a metabolite of the antidepressant and sedative trazodone.1It is an inhibitor of organic anion transporter 3 (OAT3; Ki= 16.9 μM) and is selective for OAT3 over OAT1 (Ki= >200 μM).2 1.Yamato, C., Takahashi, T., Fujita, T., et al.Studies on metabolism of trazodone, II. Metabolic fate after intravenous administration and effects on liver microsomal drug-metabolizing enzymes in ratsXenobiotica4(12)765-777(1974) 2.Zou, L., Matsson, P., Stecula, A., et al.Drug metabolites potently inhibit renal organic anion transporters, OAT1 and OAT3J. Pharm. Sci.110(1)347-353(2021)

Tyrosinase (192-200), a human mouse nonapeptide, is recognizable by cytolytic T cells (CTL) on the HLA-B44 molecule and is utilized in the research of melanoma-associated cancers [1].

Ganglioside GD3 is synthesized by the addition of two sialic acid residues to lactosylceramide and can serve as a precursor to the formation of more complex gangliosides by the action of glycosyl- and sialyltransferases. It induces apoptosis in HuT-78 cutaneous T cell lymphoma cells in a concentration-dependent manner and disrupts the mitochondrial membrane potential when used at a concentration of 200 μM. Expression of ganglioside GD3 in GD3-negative SK-MEL-28-N1 malignant melanoma cells increases both cell proliferation and invasion in vitro. Ganglioside GD3-deficient adult mice exhibit progressive loss of the neural stem cell (NSC) pool and impaired neurogenesis. Ganglioside GD3 mixture contains ganglioside GD3 molecular species with C18:1 and C20:1 sphingoid backbones.

AMK is an active metabolite of the neurohormone melatonin .1,2,3,4It is formed from melatoninviathe metabolic intermediate AFMK that is then deformylated by catalase or formamidase.5,6AMK scavenges singlet oxygenin vitrowhen used at a concentration of 200 μM.1It inhibits the epinephrine- and arachidonic acid-induced production of prostaglandin E2and PGD2in ovine seminal vesicle microsomes in a concentration- and time-dependent manner, as well as LPS-induced increases in COX-2 levels in RAW 264.7 macrophages when used at a concentration of 500 μM.2,3AMK (20 mg/kg) decreases MPTP-induced increases in lipid peroxidation in the cytosol and mitochondria from substantia nigra and striatum in a mouse model of MPTP-induced Parkinson’s disease.4 1.Schaefer, M., and Hardeland, R.The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavengerJ. Pineal Res.46(1)49-52(2009) 2.Kelly, R.W., Amato, F., and Seamark, R.F.N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesisBiochem. Biophys. Res. Commun.121(1)372-379(1984) 3.Mayo, J.C., Sainz, R.M., Tan, D.-X., et al.Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophagesJ. Neuroimmunol.165(1-2)139-149(2005) 4.Tapias, V., Escames, G., López, L.C., et al.Melatonin and its brain metabolite N1-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian miceJ. Neurosci. Res.87(13)3002-3010(2009) 5.Tan, D.-X., Manchester, L.C., Reiter, R.J., et al.Melatonin directly scavenges hydrogen peroxide: A potentially new metabolic pathway of melatonin biotransformationFree Radic. Biol. Med.29(11)1177-1185(2000) 6.Hirata, F., Hayaishi, O., Tokuyama, T., et al.In vitro and in vivo formation of two new metabolites of melatoninJ. Biol. Chem.249(4)1311-1313(1974)

CXCR3 antagonist 6c is an antagonist of chemokine (C-X-C motif) receptor 3 (CXCR3).1It inhibits calcium mobilization induced by chemokine (C-X-C motif) ligand 11 (CXCL11) in HEK293 cells expressing the human receptor (IC50= 0.06 μM). It is selective for CXCR3 over a panel of 14 human G protein-coupled receptors at 10 μM. CXCR3 antagonist 6c inhibits CXCR3-mediated migration of isolated human T cells (IC50= ~100 nM). 1.Cole, A.G., Stroke, I.L., Brescia, M.-R., et al.Identification and initial evaluation of 4-N-aryl-[1,4]diazepane ureas as potent CXCR3 antagonistsBioorg. Med. Chem. Lett.16(1)200-203(2006)

CGP60474 is an inhibitor of VEGFR-2 (IC50 = 84 nM) and an inhibitor of ATP-competitive PKC. CGP60474 is also a highly potent anti-endotoxemic agent and inhibits cyclin-dependent kinase (CDK) potently.

Paraherquamide A is a mycotoxin anthelmintic originally isolated from P. paraherquei. It binds to acetylcholine receptors (IC50 = 0.5 nM for head homogenates of M. domestica) and acts as an antagonist. Paraherquamide A is toxic to C. elegans (LD50 = 2.5 μg/ml) and effective against T. colubriformis infection in gerbils when used at doses ranging from 0.39 to 200 mg/kg. It is toxic to mice (LD50 = 14.9 mg/kg).

Terpendole I is a fungal metabolite that has been found in A. yamanashiensis.1 It is a weak inhibitor of acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 145 μM) and is active against the bacteria B. cereus and B. subtilis (MICs = 100 μg/ml for both) but not S. aureus, P. aeruginosa, or K. pneumoniae (MICs = >200 μg/ml for all) or the fungus C. albicans (MIC = 200 μg/ml).1,2 It is cytotoxic to HeLa cells with an IC50 value of 52.6 μM.3 |1. Tomoda, H., Tabata, N., Yang, D.-J., et al. Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. III. Production, isolation and structure elucidation of new components. J. Antibiot. (Tokyo) 48(8), 793-804 (1995).|2. Zhao, J.-C., Wang, Y.-L., Zhang, T.-Y., et al. Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents. Phytochemistry 148, 21-28 (2018).|3. Nagumo, Y., Motoyama, T., Hayashi, T., et al. Structure-activity relationships of terpendole E and its natural derivatives. ChemistrySelect 2(4), 1533-1536 (2017).

Oosporein is a mycotoxin that has been found inBeauveriaand has diverse biological activities.1,2It is cytotoxic to Sf9 and Sf21 insect cells with 50% cytotoxic concentration (CC50) values of 4.23 and 10.43 μM, respectively.3Oosporin induces lethality in day-old cockerels (LD50= 6.12 mg/kg).4It inhibits Na+/K+-, Ca2+-, and Mg2+-ATPase activities by 27, 52, and 100%, respectively, in equine erythrocyte ghosts when used at a concentration of 200 μg/ml.2Oosporein inhibits herpes simplex 1 (HSV-1), but not HeLa cell orE. coli, DNA polymerase (IC50s = 75, 610, and >700 μM, respectively).5It is active against the bacteriumS. pneumoniae(MIC = 32 μg/ml) and the plant pathogenic fungusP. infestans(MIC = 16 μM).1,6 1.Wainwright, M., Betts, R.P., and Teale, D.M.Antibiotic activity of oosporein from Verticillium psalliotaeTrans. Br. Mycol. Soc.86(1)168-170(1986) 2.Jeffs, L.B., and Khachatourians, G.G.Toxic properties of Beauveria pigments on erythrocyte membranesToxicon. 35(8)1351-1356(1997) 3.Arboleda Valencia, J.W., Gaitán Bustamante, A.L., Jiménez, A.V., et al.Cytotoxic activity of fungal metabolites from the pathogenic fungus Beauveria bassiana: An intraspecific evaluation of beauvericin productionCurr. Microbiol.63(3)306-312(2011) 4.Cole, R.J., Kirksey, J.W., Cutler, H.G., et al.Toxic effects of oosporein from Chaetomium trilateraleJ. Agric. Food Chem.22(3)517-520(1974) 5.Terry, B.J., Liu, W.C., Cianci, C.W., et al.Inhibition of herpes simplex virus type 1 DNA polymerase by the natural product oosporeinJ. Antibiot. (Tokyo)45(2)286-288(1992) 6.Nagaoka, T., Nakata, K., Kouno, K., et al.Antifungal activity of oosporein from an antagonistic fungus against Phytophthora infestansZ. Naturforsch. C. J. Biosci.59(3-4)302-304(2004)

Pyridaben is a METI acaricide that inhibits mitochondrial electron transport at complex I (METI; Ki = 0.36 nmol/mg protein in rat brain mitochondria).

AGN 195183 is a potent and selective agonist of RARα(Kd=3 nM) with improved binding selectivity relative to AGN 193836; no activity on RARβ/γ. IC50 value: 3 nM (Kd); 200 nM (EC80, RAR Trans.) Target: RARα agonist Compound 4(AGN-195183) inhibited the growt