at-56

AT56 是口服有活性的脂钙蛋白型前列腺素 D 合酶 (L-PGDS) 选择性抑制剂，其IC50=95 μM，Ki=75 μM。它能够特异性地抑制L-PGDS 催化的 PGD2介导的嗜睡或疼痛反应。

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

Org 25543 hydrochloride 是一种有效的选择性甘氨酸转运蛋白 2 型 (GlyT2) 抑制剂（hGlyT2 的 IC50 = 16 nM）。在 CHO 细胞的甘氨酸摄取测定中，对 GlyT1 或 56 种其他常见生物靶标 (≥ 100 μM) 没有显示活性。

Unifiram 是一种认知增强剂。 Unifiram 诱导大鼠海马 CA1 区场兴奋性突触后电位 (fEPSP) 幅度的持久增加 (EC50= 27 nM) 并增加大鼠大脑皮层中乙酰胆碱 (ACh) 的释放。

CYM50308 是选择性和高亲和力的鞘氨醇-1-磷酸受体 4 激动剂，EC50为 56 nM。它对 S1P4-R 的选择性比 S1P5-R 高 37 倍。

PROTAC CDK9 degrader-11 (Compound C3) 是一种口服有效的 PROTAC CDK9 降解剂，DC50 为 1.09 nM。在小细胞肺癌 (SCLC) 细胞中，PROTAC CDK9 degrader-11 展现出强效细胞毒性，其 IC50 达到纳摩尔水平。该化合物可以在 G0 G1 期阻滞细胞周期，并抑制 DMS114 和 DMS53 细胞的侵袭能力。此外，PROTAC CDK9 degrader-11 在 NCI-H446 异种移植小鼠模型中显示出明显的抗肿瘤活性。(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). AN3661 inhibits Plasmodium falciparum laboratory-adapted strains, Ugandan field isolates, and murine P. berghei and P. falciparum infections[1]. AN3661 is active at nanomolar (IC50=20-56 nM) concentrations against P. falciparum laboratory strains known to be sensitive (3D7) or resistant (W2, Dd2, K1, HB3, FCR3 and TM90C2B), and AN3661 is similarly active in ex vivo studies of fresh Ugandan field isolates (mean ex vivo IC50=64 nM). AN3661 shows minimal cytotoxicity against mammalian cell lines, with the CC50 60.5 μM against Jurkat cells, and all other CC50 values greater than the highest concentrations tested (25 μM or above)[1].AN3661 inhibits the stability of P. falciparum transcripts[1]. AN3661 (50-200 mg.kg; p.o.; daily for 4 days) inhibits murine P. berghei infections with ED90 (4 days) 0.34 mg kg[1].AN3661 is administered orally for 4 days, beginning on the third day of infection, the ED90 4 days after initiation of treatment is 0.57 mg kg[1]. Animal Model: P. berghei-infected mice (malaria model)[1] [1]. Sonoiki E, et al. A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue. Nat Commun. 2017;8:14574. Published 2017 Mar 6.

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide 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 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 (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. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).

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. Purfalcamine has antimalarial activity and causes malaria parasites developmental arrest at the schizont stage[1][2]. Purfalcamine has low activity against Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3)[1]. Purfalcamine (225, 450 nM) has no effect on the parasitemia in the first 32 hours. After about 40 hours, parasite level remains stable and then begins dropping[1]. Purfalcamine inhibits proliferation with EC50s of 171-259 nM for P. falciparum strains (3D7, Dd2, FCB, HB3 and W2), which indicates effectiveness against drug-resistant parasites[1]. Given that the EC50 value for P. falciparum (3D7) is 230 nM, Purfalcamine shows a therapeutic window ranging from 23-fold to 36-fold (EC50s for CHO=12.33 μM, HEp2=7.235 μM, HeLa=7.029 μM and Huh7=5.476 μM)[1]. Purfalcamine (10 mg kg; oral gavage; BID; for 6 days) demonstrates a delay in the onset of parasitemia in treated mice[1]. Purfalcamine (20 mg kg; orally gavage) exhibits a Cmax of 2.6 μM with a half-life of 3.1 hours[1]. Animal Model: Male BALB c mice, 7 weeks of age with the malaria parasite[1] [1]. Nobutaka Kato, et al. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nat Chem Biol. 2008 Jun;4(6):347-56. [2]. Rajshekhar Y Gaji, et al. Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs. Antimicrob Agents Chemother. 2014 May;58(5):2598-607.

Cambinol (SIRT1 2 Inhibitor IV) 是一种SIRT1和SIRT2的抑制剂，IC50值分别为 56 μM 和 59 μM。它是中性鞘磷脂酶的外泌体抑制剂。

Anticancer agent 56 (compound 4d) is a powerful anti-cancer compound with favorable drug-like properties. It shows significant anticancer activity against multiple cancer cell lines, with an IC50 value of less than 3 μM. Anticancer agent 56 exerts its effects by causing cell cycle arrest at the G2 M phase and activating the mitochondrial apoptosis pathway. Mechanistically, it induces the accumulation of reactive oxygen species (ROS), upregulates BAX, downregulates Bcl-2, and triggers 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).

MDL-811为SIRT6的异构激活剂，有效促进SIRT6对组蛋白H3的去乙酰化作用（H3K9Ac, H3K18Ac, 和 H3K56Ac）。该化合物在结肠癌研究中有应用价值。

3-Acetyl-6-bromocoumarin，一种香豆素，具有约56%的强抗氧化活性。

Klotho衍生肽1（KP1）(56-87)是从人类Klotho蛋白质中衍生的肽，具有扰乱TGF-β信号传导的作用。它与TGF-β受体类型1（TGFBR2）和TGF-β受体类型2（TGFBR2；Kds分别为1.41和14.6µM）结合。KP1（10 µg/ml）的预孵育抑制TGF-β在NRK-49F大鼠成纤维细胞中诱导的纤维连接蛋白和α-平滑肌肌动蛋白（α-SMA）水平的增加。在体内，KP1（每天1 mg/kg）选择性地定位于受损的肾脏，并减少血清肌酐和血尿素氮水平，这些是肾功能的标志物，同时也减少了小鼠单侧输尿管阻塞（UUO）和单侧缺血-再灌注损伤诱导的肾脏纤维化模型中的肾纤维化。

Poloxamer 122 L42 是一种由聚氧乙烯和聚氧丙烯组成的嵌段聚合物，平均分子量为 1630。其具有抗菌活性，在 1 mg mL 浓度下能抑制 56% 的 Mycobacterium avium。此化合物可以形成热可逆水凝胶，被应用于食品添加剂，并在化妆品、药品及组织工程中作为药物输送载体。