p 39

P2X3 antagonist 39 (compound 26a) 作为一种高选择性P2X3受体拮抗剂,其IC50值为54.9 nM,主要用于神经性疼痛模型的研究应用.

SNAP 398299 是一种甘丙肽受体 3 型 （Gal3）拮抗剂，具有抗焦虑和抗抑郁样作用，可用于研究情绪障碍。

This is a tuberoinfundibular neuropeptide and parathyroid hormone 2(PTH 2)-receptor agonist from hypothalmus. Synthetic TIP39 activates human and rat PTH2 receptors.

CGP 39551 is a NMDA antagonist.

Abetimus (LJP 394 free base)为一种由四个双链DNA (dsDNA) 寡核苷酸构成的免疫抑制剂，其作用机制为通过交联B细胞表面的抗dsDNA抗体，从而降低体内抗dsDNA抗体水平，具备作为系统性红斑狼疮研究工具的潜力。

3BP-3940是一种高效的成纤维细胞激活蛋白 (FAP) 靶向肽，常与放射性核素偶联用于肿瘤诊断和治疗。

Anti-HER3 ERBB3 Antibody (1P393) 是一种靶向人 HER3 ERBB3 的单克隆抗体，是一种 Mouse IgG1 抗体。

EP-3945是Mas相关G蛋白偶联受体 (MRGPR) 的激动剂，其效力超过MRGPRD小分子激动剂β-Alanine。MRGPR在炎症瘙痒和疼痛感知中扮演重要角色，同时与Gq结合（MRGPRX2、MRGPRX4、MRGPRX1与Gq偶联；MRGPRX2、MRGPRD与Gi偶联），测得EP-3945对Gq的EC50为211.6 nM。

SHP394 is an orally efficacious inhibitor of protein tyrosine phosphatase SHP2 (IC50: 23 nM).

EP39 是一种有效的HIV-1成熟抑制剂。EP39 与 Gag 的 SP1 结构域相互作用。EP39 通过与 SP1 结构域的 QVT 基序结合来降低 CA-SP1 连接的动力学，并通过稳定瞬态 α 螺旋结构来扰乱 SP1 结构域两侧的自然螺旋平衡。EP39 通过阻止HIV-1的成熟而起作用，从而阻断其感染性。

AP39 free base 是一种线粒体靶向 H（2）S 供体，可提高猪胰岛在培养中的存活率。AP39 free base 通过 AMPK-ULK1-FUNDC1 通路调节线粒体自噬，抑制细胞焦亡，并改善阿霉素诱导的心肌纤维化。

CP-394531 is an effective nonsteroidal highly selective glucocorticoid receptor antagonist.

TIP39作为一种神经肽及甲状旁腺激素受体2型(PTH2R)激动剂，在表达重组人或大鼠PTH2R的COS-7细胞中诱导cAMP积累（EC50分别为0.5和0.8 nM），以及在内源性表达PTH2R的F-11细胞中（EC50 = 1.15 nM）。在CFK2大鼠软骨细胞中，TIP39 (1 nM)诱导细胞周期在G0/G1阶段停滞，并减少软骨分化的主要调控因子Sox9的表达。此外，TIP39 (100 pmol/动物)在小鼠强迫游泳测试中减少了不动时间。

CEP-751（又名KT-6587）是一种有效的Trk抑制剂。在MBL细胞系D283中，CEP-751显示出显著的生长抑制效果（第39天，P=0.031）。在IMR5（P=0.062）和CHP-134（P=0.049）细胞系上，CEP-751也表现出了适度的生长抑制效果。此外，CEP-751在治疗CHP-134肿瘤中诱导了凋亡。CEP-751可能是治疗NBL或MBL的有用化合物。在浓度为100 nM时，CEP-751能够抑制神经营养因子受体trkA、trkB和trkC的受体酪氨酸激酶活性。CEP-751对经trkA转染的NIH3T3细胞衍生的肿瘤显示出抗肿瘤效果。

Carbazomycin A is a bacterial metabolite that has been found in Streptomyces and has diverse biological activities.1,2It is active againstS. aureus,T. asteroides, andT. mentagrophytes(MIC = 12.5 μg ml for all), as well as the plant pathogenic fungusP. oryzae(MIC = 25 μg ml). Carbazomycin A is cytotoxic to MCF-7, KB, NCI H187, and Vero cells (IC50s = 26.2, 30.1, 18.4, and 32.6 μg ml, respectively).2 1.Sakano, K.-I., Ishimaru, K., and Nakamura, S.New antibiotics, carbazomycins A and B. I. Fermentation, extraction, purification and physico-chemical and biological propertiesJ Antibiot. (Tokyo)33(7)683-689(1980) 2.Intaraudom, C., Rachtawee, P., Suvannakad, R., et al.Antimalarial and antituberculosis substances from Streptomyces sp. BCC26924Tetrahedron67(39)7593-7597(2011)

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

Collinin is a coumarin that has been found in Z. schinifolium and has diverse biological activities.1,2,3,4 It is active against drug-susceptible and -resistant strains of M. tuberculosis (MIC50s = 3.13-6.25 μg/ml).1 Collinin inhibits LPS-induced nitric oxide (NO) production (IC50 = 5.9 μM) and reduces COX-2 protein levels in RAW 264.7 cells.2 It completely inhibits aggregation of isolated rabbit platelets induced by arachidonic acid , collagen, or platelet activating factor (PAF) when used at a concentration of 100 μM.3 Dietary administration of collinin (0.05% w/w) reduces the number of mice with tumors and the number of tumors per mouse in a mouse model of colitis-related carcinogenesis.4 |1. Kim, S., Seo, H., Al Mahmud, H., et al. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46, 104-110 (2018).|2. Nguyen, P.-H., Zhao, B.T., Kim, O., et al. Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity. J. Nat. Med. 70(2), 276-281 (2016).|3. I.S., C., Lin, Y.C., Tsai, I.L., et al. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39(5), 1091-1097 (1995).|4. Kohno, H., Suzuki, R., Curini, M., et al. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int. J. Cancer 118(12), 2936-2942 (2006).

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)

NH2-c[X-R-L-S-X]-K-G-P-(D-1Nal) (化合物 39) 作为APJ激动剂表现出高亲和力，其Ki值为0.6 nM。该化合物能有效激活Gαi1，具有EC50值0.8 nM，并能募集β-arrestin2，相关EC50值为31 nM。同时，NH2-c[X-R-L-S-X]-K-G-P-(D-1Nal) 对心脏功能具有显著的延长作用。