pt 9

Betahistine dihydrochloride (Betahistine 2HCl) 是可口服的组胺 H1 受体激动剂和 H3 受体的拮抗剂，可用作血管扩张剂，用于类风湿性关节炎的研究。

CU-CPT9b (TLR8-specific antagonist 1) 是 toll 样受体 8 (TLR8) 的拮抗剂，Kd 为 21 nM。它抑制由 TLR8 激动剂 R-848 在过表达 TLR8 的 HEK-Blue 细胞中诱导的 NF-ĸB 活化，IC5​​0 值为 0.7 nM。

Betahistine (Vasomotal) 是可口服的组胺 H1 受体激动剂和 H3 受体的拮抗剂，可用作血管扩张剂，用于类风湿性关节炎的研究。

OBPt-9 是促进俄雷西定受体活性的化合物，其作用主要表现在提升俄雷西定信号的调节上。

SEPT9-IN-1（compound 8b）为 SEPT9 抑制剂，其 IC50值为 94.83 μM。此化合物对人类口腔鳞状癌细胞表现出细胞毒性，IC50值为 21 µM。

LPT-99 是一种凋亡蛋白酶活化因子 1 (APAF-1) 的拮抗剂，能够抑制蛋白酶原 9 (procaspase-9) 的激活。它还可抑制 Cisplatin 诱导的细胞凋亡 (apoptosis)，并有效减轻 Cisplatin 导致的大鼠听力损失。

KPT9274 (PAK4-IN-1) 是一种非竞争性的 PAK4 和 NAMPT 双重抑制剂（IC50= ~120 nM）。它是一种口服生物可利用的小分子。

CU-CPT-9a 是TLR8特异性拮抗剂，IC50值为 0.5 nM。

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.

Methylnissolin-3-O-glucoside ((6aR, 11 aR)-3-hydroxy-9,l0-diMethoxy pt) 是一种类黄酮，从黄芪的根中获得，具有抗炎活性。