trail

API-1 (NSC-177223) 是Akt PKB 抑制剂，可同 PH 结构域相结合并抑制 Akt 膜易位，有效降低 Akt 的磷酸化水平。它可选择性的抑制PKB，对 PKC 和 PKA 的激活无抑制作用。它可以和 TNF 相关的凋亡诱导配体协同作用从而诱导细胞凋亡。

Lexatumumab (HGS-ETR 2) 是一种靶向 TRAIL 受体 2 的人激动性单克隆抗体，具有抗癌活性， 在恶性间皮瘤中诱导细胞凋亡 (apoptosis)。Lexatumumab 可用于研究恶性胸膜间皮瘤 (MPM)。

Irigenin 可通过特异性和选择性地阻断 Extra Domain A 域的 C-C 环上α9β1和α4β1整合素结合位点，介导其抗转移作用。可通过增强胃癌细胞中促凋亡分子的表达来敏化 TRAIL 诱导的凋亡，具有抗癌作用。

TIC10 Isomer (ONC201 isomer) 是一种 TIC10 的异构体。它不能诱导 TRIAL 表达的生物学活性。

Conatumumab (AMG 655) 是一种靶向人死亡受体 5 (DR5，TRAILR2) 的单克隆激动剂抗体 ，对长型 DR5 的 Kd 为 1 nM, 对短型 DR5 的 Kd 0.8 nM。Conatumumab 通过半胱天冬酶激活在多种肿瘤类型中诱导细胞凋亡。Conatumumab 可用于研究晚期实体肿瘤。

Tigatuzumab (CS-1008) 是一种靶向 death receptor 5 (DR5) 的人源化单克隆抗体，是 TRAIL-R2 激动剂，具有抗肿瘤活性，可诱导癌细胞凋亡，可用于研究胰腺癌。

Mapatumumab (HGS-ETR1) 是一种针对 TNF 相关凋亡诱导配体受体 1 （TRAIL-R1）的全人源激动性单克隆抗体，具有抗癌活性，可诱导癌细胞凋亡。

ONC206 是一种 ONC201 的类似物，是一种多巴胺 D2- 样受体 (DRD2 3 4) 的选择性拮抗剂，其拮抗作用在纳摩尔级别。它具有广谱抗肿瘤活性。

TIC10 (ONC-201) 是一种有口服活性的， 可透过血脑屏障的，肿瘤坏死因子相关的凋亡诱导配体 TRAIL 诱导剂。它通过抑制 Akt 和 ERK，从而激活 Foxo3a 并显著诱导细胞表面 TRAIL。

BAY 61-3606 dihydrochloride (BAY 61-3606) 是一种口服有效的，ATP 竞争性的，可逆的选择性Syk 抑制剂。它降低神经母细胞瘤细胞中的 ERK1 2 和 Akt 磷酸化，也降低 K-rn 细胞裂解物中 Syk 磷酸化。它作用于乳腺癌细胞，通过下调 Mcl-1 促进 TRAIL 诱导的细胞凋亡。

Isofistularin-3, as a DNA demethylating agent, induces cell cycle arrest and sensitization to TRAIL in cancer cells. Isofistularin-3 can be used as an ADC cytotoxin.Isofistularin-3 is a direct, DNA-competitive DNMT1 inhibitor, with an IC50 of 13.5 μM.

LBW242 is a 3-mer and Smac mimetic and is an effective and orally active proapoptotic IAP inhibitor. LBW242 has activity against multiple myeloma and potentiates TRAIL- and anticancer drug-mediated cell death of ovarian cancer cells. LBW242 displays effec

Bioymifi (DR5 Activator) 是一种有效的 TRAIL 受体 DR5 激活剂，与 DR5 的胞外结构域 (ECD) 结合，Kd 为 1.2 μM。Bioymifi 可以作为一种新型的 TNF 相关凋亡诱导配体 (TRAIL) 的类似物，可作为单一的诱导剂诱导 DR5 的聚集，刺激细胞凋亡。

Narasin (sodium salt) (HainanMycin) 通过神经胶质瘤细胞中的 ER 应激诱导肿瘤坏死因子相关凋亡诱导配体 (TRAIL) 介导的细胞凋亡，并通过抑制 IκBα 的磷酸化来抑制 NF-κB 信号传导。

CaspPro is a selective activator of caspase 8 that acts by potentiating TRAIL-induced cell death.

LY303511 是 LY294002 的结构类似物，可增强 SHEP-1 神经母细胞瘤细胞的TRAIL 敏感性，还可逆地阻断 MIN6 胰岛瘤细胞中的K+电流，IC50为64.6±9.1 μM。

Azadirone is a limonoid tetranortriterpene. Azadirone can sensitize cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) through ROS-ERK-CHOP-mediated up-regulation of DR4 and DR5 signaling, down-regulation of cell survival prot

Clitocine 是一种来从蘑菇中提取的一种腺苷类似物，是一种有效的转录通读剂，是一种无义突变的抑制剂，具有抗癌活性，可诱导携带 p53 无义突变等位基因的细胞产生 p53 蛋白。Clitocine 通过促进 Mcl-1 降解来增强 TRAIL 介导的人结肠癌细胞凋亡。

Hexyl decanoate, the first trail pheromone compound identified in a stingless bee, Trigona recursa. Hexyl decanoate is dominant component of gland secretions.

PBOX-15 is a novel microtubule-targeting agent that induces apoptosis, upregulates death receptors, and enhances TRAIL-mediated apoptosis in multiple myeloma cells. It also inhibits T cell migration through post-translational modification of tubulin. Pbox

Cyclopamine-KAAD is a potent inhibitor of hedgehog signaling with an IC50 value of 20 nM in a Shh-LIGHT2 assay. It blocks binding of BODIPY-cyclopamine to cells expressing Smoothened (Smo) in a dose-dependent manner. Cyclopamine-KAAD is cell-permeable and binds to SmoA1 to promote its exit from the endoplasmic reticulum. It inhibits the invasion and migration (45.9 and 43.3% inhibition, respectively) of Bel-7402 hepatocarcinoma cells and decreases the expression of nuclear glioma-associated oncogene 1 (Gli1) and cytosolic MMP-9, pERK1, and pERK2 proteins in a dose-dependent manner. Cyclopamine-KAAD also increases TRAIL-mediated cell death in NCH82 and NCH89 human glioblastoma cultures and upregulates expression of the death receptors DR4 and DR5 in LN229 and U251 glioma cells.

Nemadipine A is an L-type calcium channel blocker that induces morphological and growth defects in wild-type C. elegans and those with hypoexpression of egl-19, which encodes the only L-type calcium channel α1-subunit in the C. elegans genome. It also inhibits L-type calcium channels in chick ciliary neurons. Nemadipine A increases TRAIL-induced cytotoxicity and synergistically enhances caspase-8 and caspase-3 activation in a concentration-dependent manner in H1299 lung adenocarcinoma cells. It also decreases Survivin expression when used alone or in combination with TRAIL in A549 cells.

Fluphenazine is a traditional antipsychotic compound that tightly binds the dopamine D2 receptor (Ki = 0.55 nM) and also reversibly inhibits calmodulin at micromolar concentrations. Fluphenazine-N-2-chloroethane is a derivative of fluphenazine that contains an alkylating chlorethylamine chain, which produces irreversible protein binding. It is a relatively selective, irreversible antagonist of D2 receptors both in vitro (IC50 = 100 nM) and in vivo, inactivating approximately 90% of D2 receptors in mice within 4 hours of treatment. Through this action, fluphenazine-B-2-chloroethane can be used to induce catalepsy in mice. It irreversibly inhibits calmodulin at higher doses (IC50 = 10 μM), which can sensitize cancer cells to TRAIL-induced apoptosis.

High affinity XIAP antagonist (Kd = 16 nM for the BIR3 domain of XIAP). Exhibits cytotoxicity in a wide range of cancer cell lines in vitro (EC50 = 13 nM in MDA-MB-231 cells). Also displays antitumor activity in a mouse breast cancer xenograft model. Enhances TRAIL-induced apoptosis in chronic lymphocytic leukemia (CLL) cells. Oost et al (2004) Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J.Med.Chem. 47 4417 PMID:15317454 |Loeder et al (2009) A novel paradigm to trigger apoptosis in chronic lymphocytic leukemia. Cancer Res. 69 8977 PMID:19920200