t 100

KRN2 bromide 是有效的、选择性的 T 细胞激活核因子 (NFAT5) 的抑制剂 (IC50= 100 nM)。KRN2 bromide 可用于研究 NFAT5-介导的慢性关节炎。

TTA-A2 是一种选择性 T 型钙通道拮抗剂，是一种有效的抗惊厥药，可减少孕烷 X 受体的激活。它对 Cav3.1 (a1G) 和 Cav3.2 (a1H) 通道在 -80 mV 和- 100 mV 保持电位上具有同样的作用，IC50 值分别为 89 和 92 nM。它可用于多种人类神经系统疾病的研究，包括睡眠障碍和癫痫。

2,5-dimethyl Celecoxib 是塞来昔布衍生物和微粒体前列腺素 E 合酶 1 (mPGES-1) 的靶向抑制剂，mPGES-1 是炎症介质 PGE2 合成途径中的关键酶。

Ara-G 是一种脱氧鸟苷 (GdR) 类似物和核苷类似物，可被 T 淋巴谱系细胞迅速转化为其相应的阿拉伯糖基鸟嘌呤核苷酸三磷酸 (araGTP)，从而抑制 DNA 合成和对 T 淋巴母细胞的选择性体外毒性细胞系以及来自 T 细胞急性淋巴细胞白血病 (ALL) 患者的新鲜分离的白血病细胞。

Pyridaben 是一种METI 杀螨剂，可抑制复合物 I 处的线粒体电子转运。它对多种螨虫具有活性，通过滤纸接触给药，在 25 mg mL、100 mg mL 和 200 mg mL 的剂量下，分别诱导 100％ 的C. malaccensis，D. farina 和T. putrescentia 死亡率。

Epoxomicin (BU-4061T,Aids010837) 是一种含环氧酮的天然产物，可穿越血脑屏障，并具有很强的抗肿瘤和抗炎活性。它是一种选择性不可逆的蛋白酶体抑制剂，抑制类胰凝乳蛋白酶的活性。

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8/9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630/624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

PAR2 (1-6) amide is a synthetic peptide agonist of proteinase-activated receptor 2 (PAR2) that corresponds to residues 1-6 of the amino terminal tethered ligand sequence of human PAR2 and residues 37-42 of the full-length sequence.1It binds to NCTC 2544 cells expressing human PAR2 (Ki= 9.64 μM in a radioligand binding assay) and induces calcium mobilization in the same cells (EC50= 0.075 μM).2PAR2 (1-6) amide (100 μM) reduces colony formation of A549 lung cancer cells.1It induces superoxide production and degranulation in isolated human eosinophils when used at a concentration of 500 μM.3PAR2 (1-6) amide (5 μmol/kg) induces tear secretion in rats when used in combination with amastatin .4 1.Bohm, S.K., Kong, W., Bromme, D., et al.Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2Biochem. J.314(Pt 3)1009-1016(1996) 2.Kanke, T., Ishiwata, H., Kabeya, M., et al.Binding of a highly potent protease-activated receptor-2 (PAR2) activating peptide, [3H]2-furoyl-LIGRL-NH2, to human PAR2Br. J. Pharmacol.145(2)255-263(2005) 3.Miike, S., McWilliam, A.S., and Kita, H.Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2J. Immunol.167(11)6615-6622(2001) 4.Nishikawa, H., Kawai, K., Tanaka, M., et al.Protease-activated receptor-2 (PAR-2)-related peptides induce tear secretion in rats: Involvement of PAR-2 and non-PAR-2 mechanismsJ. Pharmacol. Exp. Ther.312(2)324-331(2005)

Plipastatin A1是一种在B. cereus中发现的脂肽类化合物，具有酶抑制活性和免疫抑制活性。它能抑制磷脂酶A2（PLA2）、PLC和PLD（IC50分别为2.9、1.3和1.4 µM）。Plipastatin A1（100 µg/ml）能抑制LPS诱导的B细胞爆发生成和Concanavalin A诱导的T细胞爆发生成。在体内，Plipastatin A1（0.1 mg/动物）能抑制小鼠的迟发型超敏反应。

S1PL-IN-31是一种鞘氨醇-1-磷酸(S1P)裂解酶的抑制剂(IC50 = 210 nM)，同时也是Smoothened(Smo)受体的对抗剂(IC50 = 440 nM)。在体内，S1PL-IN-31 (每天2 mg/kg)能够防止实验性自身免疫性脑炎(EAE)模型大鼠中，由髓鞘少突胶质细胞糖蛋白(MOG)肽段MOG29-152诱发的颈部及胸部淋巴细胞渗透和神经肌肉虚弱。该化合物降低了大鼠的淋巴细胞总数及CD4+ T细胞、CD8+ T细胞和B细胞的水平。S1PL-IN-31 (每天3及10 mg/kg剂量)在雄性和雌性大鼠心脏和淋巴结中增加了S1P水平，并且在雌性大鼠中降低了心率。

C8 Galactosylceramide is a synthetic C8 short-chain derivative of known membrane microdomain-forming sphingolipids. It increases the amount delivered and toxicity of doxorubicin in cancerous but not non-cancerous cells when incorporated into the nanoliposomal membrane of nanoliposomal-doxorubicin. C8 Galactosylceramide induces proliferation and cytokine production by splenocytes in vitro at concentrations ranging from 100-1,000 ng ml but has no effect on natural killer T cell production in vivo. It also activates NF-κB production in C6 glioma cells when used at a concentration of 10 μM.

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)

(-)-Mycousnine is a microbial metabolite and derivative of usnic acid originally isolated fromM. nawaethat has antibacterial and antifungal activities.1,2It is active against the Gram-positive bacteriaB. subtilis,K. rhizophila, andS. aureus(MICs = 4, 8, and 4 g ml, respectively) but not the Gram-negative bacteriaE. coli,S. typhimurium, andK. pneumoniae(MICs = >128 g ml for all).2(-)-Mycousnine is also active against the fungiT. mentagrophytes,T. rubrum, andC. albicans(MICs = 25, 25, and 100 μg ml, respectively).1 1.Sassa, T., and Igarashi, M.Structures of (-)-mycousnine, (+)-isomycousnine and (+)-oxymycousnine, new usnic acid derivatives from phytopathogenic Mycosphaerella nawaeAgric. BioI. Chem.54(9)2231-2237(1990) 2.Lee, J., Lee, J., Kim, G.J., et al.Mycousfurans A and B, antibacterial usnic acid congeners from the fungus Mycosphaerella sp., isolated from a marine sedimentMar. Drugs17(7)422(2019)

Adenosine 5’-methylenediphosphate is an inhibitor of ecto-5’-nucleotidase, also known as CD73, with a Kivalue of 37 nM.1It inhibits cAMP accumulation induced by adenosine 5’-monophosphate , adenosine 5’-diphosphate , or adenosine 5’-triphosphate but not adenosine in VA-13 human fibroblasts when used at a concentration of 100 μM. Adenosine 5’-methylenediphosphate reduces proliferation of U138MG glioma cells, as well as inhibits the invasion and migration of MHCC97H hepatocellular carcinoma (HCC) cells in a migration assay.2,3It increases tumor infiltration of CD3+CD8+T cells and reduces tumor growth in a K1735 murine melanoma model when administered at a dose of 400 μg mouse.4 1.Bruns, R.F.Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosineNaunyn Schmiedebergs Arch. Pharmacol.315(1)5-13(1980) 2.Braganhol, E., Tamajusuku, A.S.K., Bernardi, A., et al.Ecto-5′-nucleotidase CD73 inhibition by quercetin in the human U138MG glioma cell lineBiochim. Biophys. Acta1770(9)1352-1359(2007) 3.Shali, S., Yu, J., Zhang, X., et al.Ecto 5′ nucleotidase (CD73) is a potential target of hepatocellular carcinomaJ. Cell Physiol.234(7)10248-10259(2018) 4.Forte, G., Sorrentino, R., Montinaro, A., et al.Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanomaJ. Immunol.189(5)2226-2233(2021)

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).

S-72是一种微管聚合抑制剂，以1, 3, 10 µM的浓度在无细胞测定中抑制微管聚合，并在MCF-7和耐紫杉醇的MCF-7/T乳腺癌细胞中降低细胞活性（IC50分别为15.64和26.32 nM）。50 nM浓度的S-72能抑制MCF-7和MCF-7/T细胞的迁移和侵袭，并减少划痕实验中的伤口闭合百分比。100 nM的S-72在MCF-7/T细胞中诱导G2/M期的细胞周期阻滞以及凋亡，并在同一浓度下抑制这些细胞中干扰素基因激活剂（STING）的激活。以每天15 mg/kg的剂量，S-72抑制了耐紫杉醇的MCF-7/T和MX-1/T小鼠异种移植模型中的肿瘤生长。

KRN2 has potential to treat NFAT5-mediated Chronic Arthritis. KRN2 is a selective inhibitor of nuclear factor of activated T cells (NFAT5), with an IC50 of 100 nM.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

Palmitoylcholine is an acyl choline.1It inhibits protein kinase C activity when used at a concentration of 100 μM.2Palmitoylcholine induces hemolysis in rat erythrocytes.3Plasma levels of palmitoylcholine are decreased in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).1 1.Germain, A., Barupal, D.K., Levine, S.M., et al.Comprehensive circulatory metabolomics in ME/CFS reveals disrupted metabolism of acyl lipids and steroidsMetabolites10(1)34(2020) 2.Nakadate, T., and Blumberg, P.M.Modulation by palmitoylcarnitine of protein kinase C activationCancer Res.47(24 Pt 1)6537-6542(1987) 3.Cho, K.S., and Proulx, P.Interactions of acyl carnitines and other lysins with erythrocytes and reconstituted erythrocyte lipoproteinsBiochim. Biophys. Acta318(1)50-60(1973)

Darinaparsin is a dimethylated arsenic linked to glutathione. It is cytotoxic to DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5-10 µM) and patient-derived primary prostate cancer cells (IC50s = 2.5-20 µM), as well as Jurkat T cell lymphoma and L540 Hodgkin lymphoma cells (IC50s = 2.7 and 1.3 µM, respectively). [1][2] It decreases the tumor-initiating subpopulation in DU145 and PC3 cells and halts the cell cycle in the G2 M phase. Darinaparsin decreases transcription of Gli-2, a transcription factor that mediates Sonic hedgehog signaling, when used at a concentration of 1.5 but not 3 µM. It decreases SHP1 phosphatase activity and increases ERK phosphorylation. [2] Darinaparsin reduces tumor growth in DU145 and PC3 prostate cancer mouse xenograft models when administered at a dose of 100 mg kg every other day.[1]

T-10418 是一种针对 G2 累积蛋白 (G2A)（亦称为 G 蛋白偶联受体GPR132）的激动剂，其 EC50 值为 0.82 μM。在小鼠初级感觉神经元中，此化合物展现出增敏效应。此外，T-10418 在小鼠模型中表现出了优良的药代动力学特性，并且在 100 μM 浓度下没有观察到明显的毒性。

KUS121 is a valosin-containing protein (VCP) modulator that inhibits VCP ATPase activity (IC50= 330 nM).1It inhibits cell death, ATP depletion, and upregulation of C/EBP-homologous protein (CHOP) induced by tunicamycin, an inducer of ER stress, in HeLa cells when used at concentrations of 20, 50, and 50 μM, respectively. KUS121 (100 μM) inhibits ATP depletion and cell death induced by oxygen-glucose deprivation (OGD) in rat primary cortical neurons in anin vitromodel of cerebral ischemia.2It reduces infarction volume and increases the latency to fall in an accelerating rotarod test in a mouse model of focal cerebral ischemia induced by transient distal middle cerebral artery occlusion (MCAO) when administered at a dose of 100 mg/kg immediately following occlusion and again at 50 mg/kg following reperfusion. KUS121 (50 mg/kg) inhibits thinning of the retinal outer nuclear layer and preserves visual function in an rd10 mouse model of retinitis pigmentosa.1 1.Ikeda, H.O., Sasaoka, N., Koike, M., et al.Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosaSci. Rep.45970(2014) 2.Kinoshita, H., Maki, T., Yasuda, K., et al.KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletionSci. Rep.9(1)11519(2019)

MK-3207是口服生物相容性的CGRP 受体拮抗剂，IC50和 Ki 分别为 0.12 nM 和 0.024 nM，对 AM1，AM2，CTR 和 AMY3 的抑制性较弱。MK-3207可用于偏头痛研究。

2-(1-(Thiophen-2-yl)ethylidene)hydrazinecarbothioamide is an antimicrobial agent.1It is active against the Gram-negative bacteriaE. coli,P. aeruginosa, andS. marcescens(MICs = 64, 100, and 70 μg/ml, respectively), the Gram-positive bacteriaS. aureus,M. luteus, andB. cereus(MICs = 130, 100, and 50 μg/ml, respectively), and the fungiC. albicans,G. candidum,T. rubrum,F. oxysporum,A. flavus, andS. brevicaulis(MICs = 69-120 μg/ml). 2-(1-(Thiophen-2-yl)ethylidene)hydrazinecarbothioamide is also a precursor in the synthesis of other antimicrobial agents, as well as compounds with anticancer activity.1,2 1.Youssef, M.S.K., and Abeed, A.A.O.Synthesis and antimicrobial activity of some novel 2-thienyl substituted heterocyclesHeterocycl. Commun.20(1)25-31(2014) 2.Gomha, S.M., Edrees, M.M., and Altalbawy, F.M.A.Synthesis and characterization of some new bis-pyrazolyl-thiazoles incorporating the thiophene moiety as potent anti-tumor agentsInt. J. Mol. Sci.17(9)1499(2016)

Pericosine A is a fungal metabolite that has been found inP. byssoidesand has anticancer activity.1It inhibits the growth of a variety of cancer cells, including breast, colon, lung, ovary, stomach, and prostate cell lines (GI50s = 0.05-24.55 μM) and increases survival in a P388 mouse xenograft model when administered at a dose of 25 mg/kg. Pericosine A inhibits EGFR by 40 to 70% when used at a concentration of 100 μg/ml. It also reacts with organosulfur compounds in skunk spray to form stable thioethers as odorless products.2 1.Yamada, T., Iritani, M., Ohishi, H., et al.Pericosines, antitumour metabolites from the sea hare-derived fungus Periconia byssoides. Structures and biological activitiesOrg. Biomol. Chem.5(24)3979-3986(2007) 2.Du, L., Munteanu, C., King, J.B., et al.An electrophilic natural product provides a safe and robust odor neutralization approach to counteract malodorous organosulfur metabolites encountered in skunk sprayJ. Nat. Prod.82(7)1989-1999(2019)

CC-90005 is a potent, selective and orally active inhibitor of protein kinase C-θ (PKC-θ), with an IC50 of 8 nM. CC-90005 shows selectivity for PKC-θ over PKC-δ (IC50=4440 nM). CC-90005 can inhibit T cell activation by IL-2 expression[1]. CC-90005 shows the exquisite selectivity of CC-90005, with IC50s for all other family members of >3 μM[1].CC-90005 is a moderate inhibitor of both CYP2C9 (IC50=8 μM) and CYP2C19 (IC50=5.9 μM) in human liver microsomes[1].CC-90005 inhibits IL-2 expression in LRS_WBC human PBMCs, with an IC50 of 0.15 μM[1].CC-90005 (1-10 μM; 24 h) inhibits T cell proliferation in PBMCs by 51% at 1 μM and 88% at 3 μM[1]. CC-90005 (3-30 mg kg; p.o. twice daily for 4 days) significantly reduces the popliteal lymph node (PLN) size in a model of chronic T cell activation[1].CC-90005 (100 mg kg; a single p.o.) significantly inhibits plasma and spleen IL-2 release by 51 and 54%, respectively[1].CC-90005 exhibits reasonable oral bioavailability (66 and 46%) and Cmax (1.18 and 1.2 μM) following oral administration (10 and 3 mg kg) in rat and dog, respectively[1].CC-90005 exhibits the mean residence time (0.52 and 2.0 h), CL (69.1 and 20.5 mL min kg) and Vss (2.11 and 2.44 L kg) following intravenous administration (2 and 1 mg kg) in rat and dog, respectively[1]. [1]. Papa P, et, al. Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005. J Med Chem. 2021 Aug 26;64(16):11886-11903.

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).

Pestalotin is a fungal metabolite originally isolated from P. cryptomeriaecola with diverse biological activities. It induces reducing sugar release in embryoless rice endosperms when used at concentrations ranging from 3 to 100 mg/L and enhances growth of rice seedlings (O. sativa) when used in combination with gibberellin A3 at concentrations ranging from 30 to 500 mg/L. Pestalotin has antifungal activity, reducing the growth of C. albicans, C. neoformans, T. rubrum, and A. fumigatus (MICs = 12.5, 50, 50, and 50 μg/ml, respectively). It is cytotoxic to HL-60, MKN45, LoVo, and A549 cells (IC50s = 64.87-182.92 μM). Pestalotin has been used as a standard for dereplication of natural products.

Petromurin C is a bis-indolyl benzenoid fungal metabolite originally isolated from the ascostromata of P. muricatus. It is cytotoxic to NS-1 mouse myeloma cells (IC50 = 33 μg/ml) and has activity against T. foetus in vitro (IC50 = 100 μg/ml).

Tetranactin is a macrotetrolide and a monovalent cation ionophore that has been found in S. aureus and has antibacterial, insecticidal, and mitogenic activities. It exhibits an equilibrium permeability ratio 1,000-fold greater for lithium than sodium or cesium ions accross bilayer membranes at low voltages. Tetranactin inhibits the growth of Gram-positive bacteria and C. miyabeanus and R. solani fungi when used at concentrations less than 0.9 μg/ml. Tetranactin (0.5-1.5 μg per insect) dose-dependently increases the mortality of adult C. chinensis weevils up to 100% and has mitogenic activity against T. telarius when sprayed onto plants with an LC50 value of 9.2 μg/ml. It reduces IL-1β- and cAMP-induced secretion of phospholipase A2 (PLA2) from rat mesangial cells (IC50s = 43 and 33 nM, respectively). Tetranactin (50 ng/ml) suppresses the proliferation of human T lymphocytes induced by allogeneic cells and IL-2 and supresses the generation of cytotoxic T lymphocytes in mixed lymphocyte cultures. In vivo, tetranactin (10 mg/animal per day) completely inhibits the formation of experimental autoimmune uveoretinitis (EAU) in rats.

Roccellic acid is a lichen secondary metabolite that has been found in R. montagnei and has antibacterial and anticancer activities.1,2 It is active against the bacteria S. gordonii and P. gingivalis (MIC = 46.9 μg/ml for both).1 Roccellic acid (100 μg/ml) inhibits proliferation of MDA-MB-231, MCF-7, and DLD-1 cancer cells by 65.3, 75.8, and 87.9%, respectively.2 |1. Sweidan, A., Chollet-Krugler, M., Sauvager, A., et al. Antibacterial activities of natural lichen compounds against Streptococcus gordonii and Porphyromonas gingivalis. Fitoterapia 121, 164-169 (2017).|2. Mishra, T., Shukla, S., Meena, S., et al. Isolation and identification of cytotoxic compounds from a fruticose lichen Roccella montagnei, and it's in silico docking study against CDK-10. Rev. Bras. Farmacogn. 27(6), 724-728 (2017).

Methylspinazarin is a naphthoquinone bacterial metabolite that has been found in Streptomyces and is an inhibitor of catechol O-methyltransferase (COMT; IC50 = 0.8 μg/ml).1 It is selective for COMT over tyrosine hydroxylase, DOPA decarboxylase, and dopamine-β-hydroxylase at 100 μg/ml. Methylspinazarin decreases blood pressure in spontaneously hypertensive rats when administered at a dose of 50 mg/kg. |1. Chimura, H., Sawa, T., Takita, T., et al. Methylspinazarin and dihydromethylspinazarin, gatechol-O-methyl transerfase inhibitors produced by Streptomyces. J. Antibiot. 26(2), 112-114 (1973).

Altemicidin is a monoterpene alkaloid originally isolated fromS. sioyaensiswith acaricidal and anticancer activities.1It is acaricidal to two-spotted spider mites (T. urticae) in a greenhouse pot test at concentrations of 10 and 100 ppm. Altemicidin inhibits the growth of murine L1210 lymphocytic leukemia and IMC carcinoma cells (IC50s = 0.84 and 0.82 μg ml, respectively). It is toxic to mice with an LD50value of 0.3 mg kg. 1.Takahashi, A., Kurasawa, S., Ikeda, D., et al.Altemicidin, a new acaricidal and antitumor substance. I. Taxonomy, fermentation, isolation and physico-chemical and biological propertiesJ. Antibiot. (Tokyo)42(11)1556-1561(1989)

AKP-11 is a sphingosine-1-phosphate receptor 1 (S1P1) agonist with an EC50 of 0.047 μM for [35S]GTPγS binding to CHO-K1 cell membranes expressing human S1P1. It reduces S1P1 surface expression and enhances Akt and ERK phosphorylation in CHO cells with S1P1-HA at a 100 nM concentration. At doses of 1.3 and 3 mg/kg, AKP-11 lowers IFN-γ and IL-17 protein levels in the spinal cord and mitigates disease severity in a rat experimental autoimmune encephalomyelitis (EAE) model. Additionally, it decreases peripheral total lymphocyte and specific T cell subsets (CD4+, CD8+, and CD26L+ T cells) counts in both EAE rats and healthy controls at a 1.3 mg/kg dosage.

Cbl-b-IN-13 (Example 520)是一种有效的Cbl-b抑制剂，显示出<100 nM的IC50值，并能够激活T细胞。

PTP1B-IN-21 是蛋白酪氨酸磷酸酶 1B (PTP1B) 的选择性抑制剂 (IC50=1.56 μM)，抑制力超出高度同源 T 细胞蛋白酪氨酸磷酸酶 (TCPTP；IC50>100 μM)，PTP1B 是抑制 2 型糖尿病的重要靶点。

Carbazomycin D is a bacterial metabolite that has been found inStreptomycesand has diverse biological activities.1,2It is active against the fungiT. asteroidesandT. mentagrophytes(MIC = 100 μg ml for both) and the bacteriumM. tuberculosis(IC50= 25 μg ml). Carbazomycin D is cytotoxic to MCF-7, KB, NCI H187, and Vero cells (IC50s = 21.3, 33.2, 12.9, and 34.3 μg ml, respectively).2 1.Naid, T., Kitahara, T., Kaneda, M., et al.Carbazomycins C, D, E and F, minor components of the carbazomycin complexJ. Antibiot. (Tokyo)40(2)157-164(1987) 2.Intaraudom, C., Rachtawee, P., Suvannakad, R., et al.Antimalarial and antituberculosis substances from Streptomyces sp. BCC26924Tetrahedron67(39)7593-7597(2011)

Piericidin B is a bacterial metabolite that has been found inS. mobaraensisand has insecticidal and antimicrobial activities.1,2,3It inhibits NADH oxidase activity in isolated bovine heart mitochondria and inhibits respiration in isolated rat liver mitochondria and isolated cockroach (P. americana) muscle mitochondria.2,3Topical application of piericidin B (4 μg insect) induces mortality in 87.5% of houseflies (M. domestica).1It induces 93.3, 100, and 100% mortality in rice stem borer (C. simples), silkworm (B. mori), and green caterpillar (P. rapae) larvae, respectively, when applied at respective concentrations of 60, 4.8, and 96 μg larva. Piericidin B is active against the fungiT. asteroides,T. rubrum,M. gypseum, andC. neoforms(MICs = 20, 10, 20, and 2 μg ml, respectively), as well as the bacteriaM. luteusandP. vulgaris(MICs = 50 and 100 μg ml, respectively). 1.Takahashi, N., Suzuki, A., Kimura, Y., et al.Isolation, structure and physiological activities of piericidin B, natural Insecticide produced by a StreptomycesAgr. Biol. Chem.32(9)1115-1122(1968) 2.Jeng, M., Hall, C., Crane, F.L., et al.Inhibition of mitochondrial electron transport by piericidin A and related compoundsBiochemistry7(4)1311-1322(1968) 3.Mitsui, T., Fukami, J.-I., Fukunaga, K., et al.Studies on piericidin. I. : Effects of piericidin A and B on mitochondrial electron transport in insect muscle comparing with rotenoneSci. Insect Control34(3)126-134(1969)