AS 602801 (Bentamapimod)   中文名称: 本塔马莫

JNK1 (IC50 = 80 nM); JNK2 (IC50 = 90 nM); JNK3 (IC50 = 230 nM)

在体外，AS602801 对血清培养的非干癌细胞和源自人胰腺癌、非小细胞肺癌、卵巢癌和胶质母细胞瘤的癌症干细胞具有细胞毒性，浓度不会损害健康人成纤维细胞的活力。此外，AS602801 可防止治疗后幸存的癌症干细胞自我更新并引发肿瘤[2]。

以不会对荷瘤小鼠的健康产生负面影响的剂量和时间表全身施用 AS602801，可减少已建立的异种移植肿瘤中癌症干细胞的数量[2]。

AS602801（也称为 Bentamapimod 和 PGL5001）是一种新型、有效的 ATP 竞争性 JNK（c-Jun N 末端激酶）抑制剂，对 JNK1、JNK2 和 JNK3 的 IC50 值为 80 nM、90 nM 和 230 nM。分别。它作为 JNK 抑制剂发挥作用，可以减少狒狒诱发的子宫内膜异位症的表面积和体积，而不会对周期长度或生殖激素的血清水平产生显着影响，也不会对内分泌系统产生任何显着的不利影响。

人 IMR90 正常成纤维细胞和人癌细胞 PANC-1、A2780 和 A549 在使用或不使用所示浓度（2.5、5 或 7.5 μM）的 Bentamapimod (AS 602801) 的情况下接受为期 3 天的治疗。使用台盼蓝作为活体染料，研究人员能够计算活细胞的数量（左图）和死细胞的百分比（右图）[2]。

Mice: The silastic capsule containing 8 μg of estradiol is implanted subcutaneously into the 5-week-old athymic (ncr/nude) ovariectomized mice after isoflurane anesthesia. Twenty-four hours later, mice were injected subcutaneously or intraperitoneally with a phosphate-buffered saline (PBS) suspension containing 8 to 10 fragments of human endometrial tissue per mouse (biopsies taken from volunteers or patients) on the ventral midline just below the umbilicus. Tissue fragments are cultured as organs for 24 hours prior to injection while being treated with 1 nM estradiol, PR, or MPA. Bentamapimod (AS 602801) is first administered orally 10 to 12 days after tissue injection. MPA is administered twice weekly by tuberculin syringe injections (200 mg/kg) along the right flank, and progesterone is administered via a slow-release silastic capsule containing 25 μg PR. Gavage administration of bentamapimod (AS 602801) is carried out for 30 days at doses of 10 mg/kg and 30 mg/kg/animal. In order to directly examine the size and number of lesions, mice are once more given general anesthesia and sacrificed by cervical dislocation after the course of treatment is complete. In order to facilitate further analysis, excised lesions from uteri are weighed and measured[3].

[1]. Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticanceragents. Chem Biol. 2014 Nov 20;21(11):1433-43.

[2]. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10;7(19):27021-32.

[3]. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016 Jan;23(1):11-23.

C25H23N5O2S

457.55

457.16

C, 65.63; H, 5.07; N, 15.31; O, 6.99; S, 7.01

848344-36-5

Solid powder

C1COCCN1CC2=CC=C(C=C2)COC3=NC=CC(=N3)C(C#N)C4=NC5=CC=CC=C5S4

XCPPIJCBCWUBNT-UHFFFAOYSA-N

InChI=1S/C25H23N5O2S/c26-15-20(24-28-22-3-1-2-4-23(22)33-24)21-9-10-27-25(29-21)32-17-19-7-5-18(6-8-19)16-30-11-13-31-14-12-30/h1-10,20H,11-14,16-17H2

2-(1,3-benzothiazol-2-yl)-2-[2-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]pyrimidin-4-yl]acetonitrile

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 0.83 mg/mL (1.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。