p-500

WAY-600 是一种有效的，选择性的，ATP 竞争型的mTOR 抑制剂，抑制重组 mTOR 酶，其 IC50=9 nM。它能够阻断 mTOR 复合物 1 2 (mTORC1 2) 组装和激活。

Quinine sulfate dihydrate 在钾通道阻滞剂中起主要作用。它也被用作抗疟疾、抗胆碱能、抗高血压和降糖药。它抑制线粒体atp 调节的钾通道。它也被用来研究生物结晶血红素，血红素，在疟疾寄生虫的代谢和研究血红素(FP)复合物的毒性。

HDAC-IN-87 (Compound XII6) 是一种非选择性HDAC抑制剂，其对HDAC4和HDAC6的pIC50分别为6.9和5.8。HDAC-IN-87 对P. sorghi和P. pachyrhizi展现出杀菌活性。在雄性和雌性大鼠中的急性口服LD50均大于500 mg kg。

β-Defensin-2 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.1It inhibits the growth of periodontopathogenic and cariogenic bacteria, includingP. gingivalisandS. salivarius.2β-Defensin-2 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes.3It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-2 induces IL-31 production by human peripheral blood-derived mast cellsin vitrowhen used at a concentration of 10 μg/ml and by rat mast cellsin vivofollowing a 500 ng intradermal dose.4Expression of β-defensin-2 is increased in psoriatic skin and chronic wounds.5,6 1.Lehrer, R.I.Primate defensinsNat. Rev. Microbiol.2(9)727-738(2004) 2.Ouhara, K., Komatsuzawa, H., Yamada, S., et al.Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cellsJ. Antimicrob. Chemother.55(6)888-896(2005) 3.Niyonsaba, F., Ushio, H., Nakano, N., et al.Antimicrobial peptides human β-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokinesJ. Invest. Dermatol.127(3)594-604(2007) 4.Niyonsaba, F., Ushio, H., Hara, M., et al.Antimicrobial peptides human β-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cellsJ. Immunol.184(7)3526-3534(2010) 5.Huh, W.-K., Oono, T., Shirafuji, Y., et al.Dynamic alteration of human β-defensin 2 localization from cytoplasm to intercellular space in psoriatic skinJ. Mol. Med. (Berl.)80(10)678-684(2002) 6.Butmarc, J., Yufit, T., Carson, P., et al.Human β-defensin-2 expression is increased in chronic woundsWound Repair Regen.12(4)439-443(2004)

β-Defensin-3 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It inhibits the growth of the periodontopathogenic and cariogenic bacteria F. nucleatum, S. mutans, S. sobrinus, S. salivarius, and L. casei (MICs = 12.5-100 mg/l). It also inhibits the growth of S. aureus, S. pyogenes, P. aeruginosa, E. coli, and C. albicans. β-Defensin-3 stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes when used at a concentration of 30 μg/ml. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 5, and 20 μg/ml, respectively. β-Defensin-3 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose.

β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It induces migration of monocytes in vitro when used at a concentration of 10 nM but does not affect migration of neutrophils and eosinophils. β-Defensin-4 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-4 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose. It also inhibits growth of E. coli, P. aeruginosa, and S. aureus with lethal concentration (LC) values of 5, 12, and 15 μM, respectively, of S. carnosus (MIC = 4.5 μg/ml), and of C. albicans with a minimum fungicidal concentration (MFC) value of 7.5 μM.

DCVC inhibits pathogen-stimulated TNF-α in human extra placental membranes in vitro.Target: TNF-αin vitro: DCVC inhibits pathogen stimulated cytokine release from tissue punch cultures. DCVC (5-50 μM) significantly inhibits LTA-, LPS-, and GBS-stimulated cytokine release from tissue cultures as early as 4 h (P ≤ 0.05). In contrast, TCA (up to 500 μM) does not inhibit LTA-stimulated cytokine release from tissue punches. DCVC effects on LTA-stimulated and LPS-stimulated TNF-α release from tissue punch cultures of extraplacental membranes. DCVC effects on GBS-stimulated release of pro-inflammatory cytokines from extraplacental membranes in transwell cultures. [1]. Boldenow E, et al. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro. Reprod Toxicol. 2015 Apr;52:1-6. [2]. Lash LH, et al. Multigenerational study of chemically induced cytotoxicity and proliferation in cultures of human proximal tubular cells. Int J Mol Sci. 2014 Nov 18;15(11):21348-65. [3]. Yoo HS, et al. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects. J Toxicol Environ Health A. 2015;78(1):32-49.

Givinostat(ITF-2357)是一种非选择性和口服活性的HDAC抑制剂，能够抑制STAT5磷酸化，对crlf2重排的BCP-ALL具有抗肿瘤活性并诱导凋亡。Givinostat具有抗炎活性，在endotoxin刺激的PBMCs中抑制TNF-α和IL-1β，还能够促进β细胞的存活，可用于糖尿病、急性淋巴细胞白血病和关节炎。

Urotensin II is a peptide vasoconstrictor and agonist of the urotensin (UT) receptor (Ki= 2.06 nM for the human recombinant receptor expressed in HEK293 cells).1It stimulates intracellular calcium mobilization in HEK293 cells expressing human and rat UT (EC50s = 0.47 and 0.78 nM, respectively) but decreases intracellular calcium concentration in goby (G. mirabilis) enterocytes when used at a concentration of 500 nM.2Urotensin II (20 mU/ml) stimulates active sodium and chloride absorption across isolated goby posterior intestine in 5% seawater-adapted solution.3In vivo, urotensin II (1.5-150 nmol/kg) decreases diastolic blood pressure and increases heart rate in anesthetized rats.4It also reduces the pressor responses to sympathetic nerve stimulation, norepinephrine , and vasopressin in pithed rats when administered at a dose of 150 nmol/kg. 1.Ames, R.S., Sarau, H.M., Chambers, J.K., et al.Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14Nature401(6750)282-286(1999) 2.Loretz, C.A., and Assad, J.A.Urotensin II lowers cytoplasmic free calcium concentration in goby enterocytes: Measurements using quin2Gen. Comp. Endocrinol.64(3)355-361(1986) 3.Loretz, C.A., Freel, R.W., and Bern, H.A.Specificity of response of intestinal ion transport systems to a pair of natural peptide hormone analogs: Somatostatin and urotensin IIGen. Comp. Endocrinol.52(2)198-206(1983) 4.Gibson, A., Wallace, P., and Bern, H.A.Cardiovascular effects of urotensin II in anesthetized and pithed ratsGen. Comp. Endocrinol.64(3)435-439(1986)

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.

Neohydroxyaspergillic acid is a fungal metabolite produced by A. sclerotiorum that has antibiotic and antifungal activities. It inhibits the growth of P. aeruginosa, M. smegmatis, S. aureus, E. coli, K. pneumoniae, B. mycoides, and B. subtilis bacteria (MICs = 125-500 μg/ml). Neohydroxyaspergillic acid also inhibits the growth of G. convolute, S. consortiale, P. blakesleeanus, C. globosum, and T. mentagrophytes (MICs = 175-700 μg/ml) but not A. niger, P. notatum, M. verrucaria, or S. cerevisiae fungi.

WYE-354 是一种 ATP 竞争性的mTOR 抑制剂，IC50为 5 nM。它抑制PI3Kα和PI3Kγ，IC50分别为 1.89 μM 和 7.37 μM，也抑制mTORC1和mTORC2。它在体外能诱导自噬激活。

WYE-687 是 ATP 竞争性的 mTOR 抑制剂，其 IC50=7 nM。它能够抑制PI3Kα和PI3Kγ，IC50分别为 81 nM 和 3.11 μM。它能够抑制mTORC1和mTORC2活化。

Oxanosine is an analog of guanosine that has been found in S. capreolus and has diverse biological activities, including antibacterial, antiviral, and anticancer properties. It is active against a variety of bacteria, including S. flexneri, P. mirabilis, and E. coli (MICs = 6.25, 12.5, 25 µg ml, respectively, on peptone, but not nutrient, agar). Oxanosine inhibits replication of the HIV-1 strain IIIb in infected CEM and U937, but not H9, cells (EC50s = 7, 27, and >500 µg ml, respectively). It also inhibits the growth of HeLa human cervical cancer cells (IC50 = 32 µg ml) and reduces tumor growth in a murine L1210 lymphocytic leukemia model.