as-35

AS-35 是一种可口服且具有选择性和高效性的 leukotrienes 拮抗剂，抑制 LTC4，LTD4 和 LTE4 诱导的回肠收缩。AS-35 具有抗过敏作用，抑制白三烯合成。

As-358 对埃博拉病毒 (IC50 = 47.5 μM) 和马尔堡病毒 (IC50 = 3.7 μM) 具有抑制作用。

As-358 (hydrochloride) 显示出良好的体内安全性，并且抑制埃博拉病毒和马尔堡病毒，IC50值分别为 9.1 μM 和 18.1 μM。

5-(N,N-Hexamethylene)-amiloride (5-HMA) 是 amiloride 的衍生物，也是 Na+ H+交换抑制剂，可降低白血病细胞的细胞内 pH (pHi) 并诱导凋亡。

Lycopene (ψ,ψ-Carotene) 是一种番茄及其产品和其他红色水果和蔬菜中天然存在的类胡萝卜素，具有抗氧化活性。

Aleuritic Acid (9,10,16-trihydroxy-palmitic acid) 是紫胶中的一种主要成分，可用于香料工业。

Farudodstat (ASLAN003) 是一种具有口服活性的二氢乳清酸脱氢酶 (DHODH) 抑制剂，对人 DHODH 酶的IC50为 35 nM。它通过激活 AP-1 转录因子来抑制蛋白质合成，可以诱导凋亡，并在急性髓样白血病异种移植小鼠中大大延长其生存期。

Menaquinone-7 (Vitamin K2(35)) 是一种最早作为抗出血因子被发现的维生素K2家族成员。它是Gla-蛋白羧化反应中最具生物活性的辅因子，补充它也是激活Gla 基质蛋白并干预钙化性主动脉瓣狭窄(CAVS)进展的一种药理选择。

Tyrosinase-IN-35（compound 6g）作为一种优于Kojic Acid（IC50: 16.38 μM）的人类酪氨酸酶抑制剂（IC50: 2.09 μM），在4 μM及8 μM剂量下已证实可以有效减少黑色素瘤细胞B16F10体外的黑色素含量。

URAT1&XO inhibitor 3（化合物27）是一种针对XO（IC50：35 nM）和URAT1（IC50：31 nM）的口服抗痛风药物，展示出优良的药理学及药物动力学（PK）属性，并具备良好的体内安全性。

LSD1-IN-35 (Compound Z-1) 作为一种高选择性的LSD1抑制剂，其IC50值为108 nM，能够有效抑制H3K4me1 2的去甲基化。此化合物还表现出免疫调节功能，通过减少PD-L1表达，增强胃癌细胞对T细胞杀伤作用的敏感性，并有效减弱PD-1 PD-L1之间的相互作用。

CDK9-IN-35 (compound 10j) 作为CDK9 CyclinT1的抑制剂，展现出极佳的抑制效果，其IC50值仅为 10.2 nM。在HCT-116细胞系中，该化合物的IC50值为 20 nM。

SMARCA2 ligand-8 是一种针对SMARCA2靶蛋白的配体，主要应用于PROTAC SMARCA2 4-degrader-35的合成。

Purine riboside-5'-O-triphosphate sodium 是 Nebularine (HY -103694) 的活性代谢产物，作为 DNA 引物酶 ATP 和 GTP 聚合活性的抑制剂，其IC50值分别为 35 µM 和 28 µM。此外，Purine riboside-5'-O-triphosphate sodium 还能抑制钙调素依赖性蛋白激酶II (calmodulin-dependent protein kinase II (CaMKII))，其Ki值为 590 µM。

SHP2-IN-35 (Compound 3f) 是一种SHP2抑制剂，在癌细胞 RKO、SW480 和 CT26 中表现出抗增殖活性，IC50分别为 5.72 μM、3.71 μM 和 1.42 μM。该化合物抑制PI3K-Akt信号通路，调节细胞周期相关基因的表达，诱导线粒体自噬 (autophagy)，并在肿瘤微环境 (TME) 中抑制某些细胞因子和趋化因子的表达，从而调节肿瘤进展。

H-Arg-Gly-Asp-Cys-OH is a tetrapeptide that contains the arginine-glycine-aspartate (RGD) motif, a sequence that acts as a recognition site for various adhesion proteins.1It inhibits the binding of fibrinogen to endothelial cells and ADP-stimulated platelets with IC50values of 320 and 35 μM, respectively.2Implantation of titanium rods coated with H-Arg-Gly-Asp-Cys-OH increases bone formation in rat femurs.3H-Arg-Gly-Asp-Cys-OH has been conjugated to polyethylenimine to improve gene transfection efficiency.4 1.Park, H.S., Kim, C., and Kang, Y.K.Preferred conformations of RGDX tetrapeptides to inhibit the binding of fibrinogen to plateletsBiopolymers63(5)298-313(2002) 2.Tranqui, L., Andrieux, A., Hudry-Clergeon, G., et al.Differential structural requirements for fibrinogen binding to platelets and to endothelial cellsJ. Cell Biol.108(6)2519-2527(1989) 3.Ferris, D.M., Moodie, G.D., Dimond, P.M., et al.RGD-coated titanium implants stimulate increased bone formation in vivoBiomaterials20(23-24)2323-2331(1999) 4.Kunath, K., Merdan, T., Hegener, O., et al.Integrin targeting using RGD-PEI conjugates for in vitro gene transferJ. Gene Med.5(7)588-599(2003)

HT-2 toxin-13C22is intended for use as an internal standard for the quantification of HT-2 toxin by GC- or LC-MS. HT-2 toxin is a type A trichothecene mycotoxin and an active, deacetylated metabolite of the trichothecene mycotoxin T-2 toxin .1,2Like T-2 toxin, HT-2 toxin inhibits protein synthesis and cell proliferation in plants.2HT-2 toxin also reduces viability of HepG2, A549, HEp-2, Caco-2, A-204, U937, Jurkat, and RPMI-8226 cancer cells with IC50values ranging from 3.1 to 23 ng ml and human umbilical vein endothelial cells with an IC50value of 56.4 ng ml.1It induces oxidative stress, DNA damage, and autophagy in, as well as halts the development of, cultured mouse embryos when used at a concentration of 10 nM.3HT-2 toxin has been found in cereal grains and food products.4,5 1.Nielsen, C., Casteel, M., Didier, A., et al.Trichothecene-induced cytotoxicity on human cell linesMycotoxin Res.25(2)77-84(2009) 2.Nathanail, A.V., Varga, E., Meng-Reiterer, J., et al.Metabolism of the fusarium mycotoxins T-2 toxin and HT-2 toxin in wheatJ. Agric. Food Chem.63(35)7862-7872(2015) 3.Zhang, L., Li, L., Xu, J., et al.HT-2 toxin exposure induces mitochondria dysfunction and DNA damage during mouse early embryo developmentReprod. Toxicol.85104-109(2019) 4.Langseth, W., and Rundberget, T.The occurrence of HT-2 toxin and other trichothecenes in Norwegian cerealsMycopathologia147(3)157-165(1999) 5.Al-Taher, F., Cappozzo, J., Zweigenbaum, J., et al.Detection and quantitation of mycotoxins in infant cereals in the U.S. market by LC-MS MS using a stable isotope dilution assayFood Control72(Part A)27-35(2017)

Deoxy donepezil is a potential impurity found in bulk preparations of the acetylcholinesterase inhibitor donepezil .1It is produced as a by-product during donepezil synthesis.2 1.Krishna Reddy, K.V.S.R., Moses Babu, J., Anil Kumar, P., et al.Identification and characterization of potential impurities of donepezilJ. Pharm. Biomed. Anal.35(5)1047-1058(2004) 2.Krizmanic, I., Lerman, L., Samardzic, Z., et al.Impurities of donepezil(2009)

Resolvins are a family of potent lipid mediators derived from both eicosapentaenoic acid and docosahexaenoic acid.[1] In addition to being anti-inflammatory, resolvins promote the resolution of the inflammatory response back to a non-inflamed state.[2] Resolvin D1 is produced physiologically from the sequential oxygenation of DHA by 15- and 5-lipoxygenase.[1] 17(R)-RvD1 is an aspirin-triggered epimer of RvD1 that reduces human polymorphonuclear leukocyte (PMN) transendothelial migration, the earliest event in acute inflammation, with equipotency to RvD1 (EC50 = ~30 nM).[3] 17(R)-RvD1 exhibits a dose-dependent reduction in leukocyte infiltration in a mouse model of peritonitis with maximal inhibition of ~35% at a 100 ng dose.[3] In contrast to RvD1, the aspirin-triggered form resists rapid inactivation by eicosanoid oxidoreductases. Analytical and biological comparisons of synthetic 17(R)-RvD1 with endogenously derived 17(R)-RvD1 have confirmed its identity as matching the natural product.[4]

Citarinostat (ACY241) 是一种强效、选择性和口服组蛋白脱乙酰酶 (HDAC) 抑制剂，具有抗肿瘤活性，对 HDAC1、HDAC2、HDAC3、HDAC6 和 HDAC8 的 IC50分别为 35、45、46、2.6 和 137 nM。

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1 2 by MEK1 2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0 G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1 2 by MEK1 2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0 G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

Lysosphingomyelin is an endogenous bioactive sphingolipid and a constituent of lipoproteins.1,2It is produced by the removal of the acyl group from sphingomyelin by a deacylase and acts as a precursor in the biosynthesis of sphingosine-1-phosphate . D-erythroLysosphingomyelin is an agonist of the S1P receptors S1P1, S1P2, and S1P3(EC50s = 167.7, 368.1, and 482.6 nM, respectively, for the human receptors).3It is also an agonist of the orphan receptor ovarian cancer G protein-coupled receptor 1 (ORG1) that induces calcium accumulation in cells overexpressing OGR1 (EC50= ~35 nM).4Levels of D-erythrolysosphingomyelin are increased in skin isolated from patients with atopic dermatitis, as well as postmortem brain from patients with Niemann-Pick disease type A, but not type B.2,5L-threolysosphingomyelin is also an S1P1-3agonist (EC50s = 19.3, 131.8, and 313.3 nM, respectively).3This product is a mixture of D-erythroand L-threolysosphingomyelin. [Matreya, LLC. Catalog No. 1321] 1.Ito, M., Kurita, T., and Kita, K.A novel enzyme that cleaves the N-acyl linkage of ceramides in various glycosphingolipids as well as sphingomyelin to produce their lyso formsJ. Biol. Chem.270(41)24370-24374(1995) 2.Nixon, G.F., Mathieson, F.A., and Hunter, I.The multi-functional role of sphingosylphosphorylcholineProg. Lipid Res.47(1)62-75(2008) 3.Im, D.-S., Clemens, J., Macdonald, T.L., et al.Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): Structure-activity relationship of sphingosine1-phosphate receptorsBiochemistry40(46)14053-14060(2001) 4.Meyer zu Heringdorf, D., Himmel, H.M., and Jakobs, K.H.Sphingosylphosphorylcholine-biological functions and mechanisms of actionBiochim. Biophys. Acta1582(1-3)178-189(2002) 5.Rodriguez-Lafrasse, C., and Vanier, M.T.Sphingosylphosphorylcholine in Niemann-Pick disease brain: Accumulation in type A but not in type BNeurochem. Res.24(2)199-205(1999)

p38 MAPK inhibitor (IC50 = 0.38 μM). Inhibits the release of IL-1β and TNF-α in a peripheral blood mononuclear cell (PBMC) assay (IC50 values are 0.039 and 0.16 μM respectively). Laufer et al (2003) Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J.Med.Chem. 46 3230 PMID:12852754 |Kammerer et al (2007) Pharmacokinetics of ML3403 ({4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenylethyl)-amine), a 4-pyridinylimidazole-type p38 mitogen-activated protein kinase inhibitor. Drug Metab.Dispos. 35 875 PMID:17344341

Australine is a pyrrolizidine alkaloid originally isolated fromC. australethat has enzyme inhibitory activities.1,2,3It is an inhibitor of glucoamylase (IC50= 5.8 μM) that also inhibits glucosidase I, sucrase, maltase, andA. nigerα-glucosidase (IC50s = 20, 28, 35, and 28 μM, respectively).2,3Australine is selective for these enzymes over glucosidase II, α- and β-mannosidase, and α- and β-galactosidase up to 500 μM, β-glucosidase, with only 5% inhibition at 66 μM, as well as isomaltase and trehalase (IC50= 97 and 160 μM, respectively). Australine (500 μg/ml) inhibits glycoprotein processing of viral glycoproteins in influenza virus-infected MDCK cells and induces the accumulation of glycoproteins.2 1.Molyneux, R.J., Benson, M., Wong, R.Y., et al.Australine, a novel pyrrolizidine alkaloid glucosidase inhibitor from Castanospermum australJ. Nat. Prod.51(6)1198-1206(1988) 2.Tropea, J.E., Molyneux, R.J., Kaushal, G.P., et al.Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processingBiochemistry28(5)2027-2034(1989) 3.Kato, A., Kano, E., Adachi, I., et al.Australine and related alkaloids: easy structural confirmation by 13C NMR spectral data and biological activitiesTetrahedron Asymmetry14(3)325-331(2003)