k-13

K-13 is used as an ACE inhibitor produced by Micromonospora halophytics subsp. exilisia K-13.

K 13-004 is a lipid-lowering agent.

2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005). 2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2 References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005).

Novel oxylipins, referred to as docosanoids, have been derived from C22polyunsaturated fatty acids 7(S),17(S)-dihydroxy-8(E),10(Z),13(Z),15(E),19(Z)-Docosapentaenoic acid (7(S),17(S)-hydroxy DPA) is a DPA-derived analog of the 17(S)-dihydroxy series of docosanoids known as protectins. Protectin D1, a DHA-derived dihydroxy fatty acid, exhibits potent anti-inflammatory activities.1,2,3Potentially, 7(S),17(S)-hydroxy DPA demonstrates similar properties; however, its biological activity has yet to be determined. 1.Serhan, C.N., Gotlinger, K., Hong, S., et al.Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: Assignments of dihydroxy-containing docosatrienesJ. Immunol.176(3)1848-1859(2006) 2.Ariel, A., and Serhan, C.N.Resolvins and protectins in the termination program of acute inflammationTRENDS in Immunology28(4)176-183(2007) 3.Schwab, J.M., Chiang, N., Arita, M., et al.Resolvin E1 and protectin D1 activate inflammation-resolution programmesNature447(7146)869-874(2007)

Ibuprofen Impurity K is a compound that serves as an impurity in Ibuprofen. Ibuprofen itself is an anti-inflammatory inhibitor specifically designed to target COX-1 and COX-2. It exhibits inhibitory activity with IC50 values of 13 μM and 370 μM for COX-1 and COX-2, respectively.

Hemitoxin, a scorpion-venom peptide, acts as a K+ channel blocker, selectively inhibiting rat Kv1.1, Kv1.2, and Kv1.3 channels expressed in Xenopus oocytes, with IC50 values of 13 nM, 16 nM, and 2 nM, respectively [1].

[Lys8, Lys9]-Neurotensin (8-13) (JMV438) is a Neurotensin analog that elicits analgesic effects by activating the G protein-coupled receptors NTS1 and NTS2, with K i values of 0.33 nM and 0.95 nM for hNTS1 and hNTS2 receptors, respectively.

CDDD11-8 is an orally administered, highly potent and selective CDK9 and FLT3-ITD inhibitor, with K i values of 8 nM and 13 nM, respectively. It effectively reduces the proliferation of leukemia cell lines, showing particular efficacy against those with the FLT3-ITD mutation [1] [2].

RGH-122 (compound 43), characterized as an orally active, potent, and selective hV1a receptor antagonist, demonstrates significant affinity with a K i value of 0.3 nM and an IC 50 of 0.9 nM. It exhibits microsomal stability, indicated by a CL int value of 13 28 25 μL min mg [1].

Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011). Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4 References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011).

Human carbonic anhydrase II-IN-24 (Compound R-13) is a potent human carbonic anhydrase (hCA) inhibitor. Human carbonic anhydrase II-IN-24 shows K i s of 60.7, 320.7, 2298, and 35.2 nM for hCA I, II, IV and IX, respectively.

Carbonic anhydrase inhibitor 8 (compound R-13) is a potent human carbonic anhydrase (hCA) with K i values of 60.7 nM, 320.7 nM, and 2298 nM for hCA I, hCA II, and hCA IV, respectively.

Hirsutide is a cyclotetrapeptide fungal metabolite produced by the entomopathogenic fungus Hirsutella. It has antibacterial activity against C. pyogenes, S. aureus, P. aeruginosa, and K. pneumonia (MICs = 25, 13, 6, and 21 μg/cm3, respectively). Hirsutide also has antifungal activity against C. albicans, M. audouinii, A. niger, and Ganoderma (MICs = 13, 6, 25, and 6 μg/cm3, respectively).

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

Chloroprocaine hydrochloride (Chloroprocaine HCl) is a local anesthetic during surgical procedures.

ent-3-Acetoxy-labda-8(17),13-dien-15-oic acid have vasorelaxant and hypotensive actions, the mechanisms underlying the cardiovascular actions of the labdane involve the activation of the endothelial NO-cGMP pathway, the opening of K+ channels and the alteration on Ca2+ mobilization.

WLB-89462 (Compound 20c) is a selective σ2 receptor ligand with a K i of 13 nM, demonstrating neuroprotective properties and the capacity to ameliorate Aβ peptide-induced short-term memory impairment in rats. It exhibits a favorable ADMET profile, featuring good solubility, lack of CYP inhibition, strong metabolic stability, high permeability, effective brain penetration, and significant oral exposure in rodent models [1].

Dot1L-IN-1 TFA is a potent and selective Dot1L inhibitor, with a K i of 2 pM and an IC50 of <0.1 nM. It effectively inhibits H3K79 dimethylation (IC50 = 3 nM) and suppresses HoxA9 promoter activity (IC50 = 17 nM) in HeLa and Molm-13 cells, respectively [1].

AZT triphosphate TFA (3'-Azido-3'-deoxythymidine-5'-triphosphate TFA) is a active triphosphate metabolite of Zidovudine (AZT). AZT triphosphate TFA exhibits antiretroviral activity and inhibits replication of HIV. AZT triphosphate TFA also inhibits the DNA polymerase of HBV. AZT triphosphate TFA activates the mitochondria-mediated apoptosis pathway[1][2][3]. Treatment with 100 μM Zidovudine (AZT) for 48h disrupts the mitochondrial tubular network via accumulation of AZT triphosphate (AZT-TP) in H9c2 cells. AZT triphosphate accumulation causes downregulation of Opa1 and upregulation of Drp1. AZT triphosphate causes mitochondrial dysfunction, increases the production of cytotoxic reactive oxygen species (ROS), and impairs the balance of the mitochondrial quality control system in H9c2 cell model established from rat embryonic myoblasts[1]. [1]. Ryosuke Nomura, et al. Azidothymidine-triphosphate Impairs Mitochondrial Dynamics by Disrupting the Quality Control System. Redox Biol. 2017 Oct;13:407-417. [2]. Takeya Sato, et al. Engineered Human tmpk/AZT as a Novel Enzyme/Prodrug Axis for Suicide Gene Therapy. Mol Ther. 2007 May;15(5):962-70. [3]. K Y Hostetler, et al. Enhanced Oral Absorption and Antiviral Activity of 1-O-octadecyl-sn-glycero-3-phospho-acyclovir and Related Compounds in Hepatitis B Virus Infection, in Vitro. Biochem Pharmacol. 1997 Jun 15;53(12):1815-22.

Gliovirin is a fungal metabolite that has been found inT. harzianumand has fungicidal, antimicrobial and anti-inflammatory activities.1It is active against the plant pathogenic fungusP. ultimum(MIC = 60 ng/ml) and the parasiteT. brucei brucei(IC50= 90 ng/ml), but has no effect on the plant pathogenic fungiR. solani,P. omnivorum,T. basicola,R. arrhizus, andV. dahliaeor the bacteriaB. thuringiensis,P. fluorescens, andX. malvacearumwhen used at concentrations up to 1,000 ng/ml.2,3Gliovirin decreases phorbol 12-myristate 13-acetate (TPA)- and ionomycin-induced increased expression of COX-2 (IC50= 1 μM) and protein levels of IL-2 in Jurkat cells (IC50= 5.2 μM).1 1.Rether, J., Serwe, A., Anke, T., et al.Inhibition of inducible tumor necrosis factor-α expression by the fungal epipolythiodiketopiperazine gliovirinBiol. Chem.388(6)627-637(2007) 2.Howell, C.R., and Stipanovic, R.D.Gliovirin, a new antibiotic from Gliocladium virens, and its role in the biological control of Pythium ultimumCan. J. Microbiol.29(3)321-324(1983) 3.Iwatsuki, M., Otoguro, K., Ishiyama, A., et al.In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationshipsJ. Antibiot. (Tokyo)63(10)619-622(2010)

5'-pApA is a linearized form of cyclic di-AMP, a bacterial second messenger that activates the host innate immune system through stimulator of interferon genes (STING).1,2,3,4It is a metabolite of cyclic di-AMP formedviahydrolysis by various phosphodiesterases (PDEs).55'-pApA is intended for use as a negative control for cyclic di-AMP signaling. 1.Burdette, D.L., Monroe, K.M., Sotelo-Troha, K., et al.STING is a direct innate immune sensor of cyclic-di-GMPNature478(7370)515-518(2011) 2.Parvatiyar, K., Zhang, Z., Teles, R.M., et al.DDX41 recognizes bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune responseNat. Immunol.13(12)1155-1161(2012) 3.Woodward, J.J., Iavarone, A.T., and Portnoy, D.A.c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon responseScience328(5986)1703-1705(2010) 4.Witte, C.E., Whiteley, A.T., Burke, T.P., et al.Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infectionmBio4(3)e00282-00213(2013) 5.Fahmi, T., Port, G.C., and Cho, K.H.c-di-AMP: An essential molecule in the signaling pathways that regulate the viability and virulence of gram-positive bacteriaGenes (Basel)8(8)197(2017)

Chloroprocaine (2-Chloroprocaine) is an effective Na,K-ATPase activity inhibitor with an IC 50 of 13 mM. Chloroprocaine is a local anesthetics that block peripheral nerve [1].

Nociceptin (1-13), amide TFA, a potent ORL1 receptor (opioid receptor-like 1 receptor, OP4) agonist, exhibits a pEC50 of 7.9 in mouse vas deferens and a Ki of 0.75 nM for rat forebrain membrane binding [1] [2].

Compound 10, an hNTS1R agonist-1, acts as a full agonist with a strong affinity for hNTS1R (K i: 6.9 nM), showing the ability to cross the blood-brain barrier (BBB). It not only enhances motor function but also improves memory in a mouse model of Parkinson's disease (PD). Additionally, this compound is an analog of Neurotensin(8-13) and demonstrates neuroprotective properties [1].

hCAII-IN-6 (Compound S-13), a potent inhibitor of human carbonic anhydrase II (hCA II) with a K i of 4.4 nM, also exhibits inhibitory activity against other hCA isoforms, namely I, IV, and IX, with K i values of 9.2 nM, 480.2 nM, and 14.7 nM, respectively. It is utilized in glaucoma research [1].

Callosobruchusic acid is an insect pheromone and monoterpene that has been found as a component of the copulation release pheromone erectin in azuki bean weevils (C. chinensis).1It induces copulation release activity in male azuki bean weevils (EC50= 6.5 ng/insect). 1.Mori, K., Ito, T., Tanaka, K., et al.Synthesis and biological activity of optically active forms of (E)-3, 7-dimethyl-2-octene-1, 8-dioic acid (callosobruchusic acid): A component of the copulation release pheromone (erectin) of the azuki bean weevilTetrahedron39(13)2303-2306(1983)

Obafluorin is a β-lactone antibiotic that has been found in P. fluorescens.1 It is active against S. aureus, S. faecalis, K. pneumoniae, and P. vulgaris (MIC = 125 μg/ml for all). |1. Pu, Y., Lowe, C., Sailer, M., et al. Synthesis, stability, and antimicrobial activity of (+)-obafluorin and related β-lactone antibiotics. J. Org. Chem. 59(13), 3642-3655 (1994).