Serdemetan (JNJ-26854165)
Serdemetan (JNJ-26854165)是一种HDM2泛素连接酶拮抗剂，作用于p53野生型细胞，诱导早期凋亡，在缺乏功能性p53的细胞中，抑制细胞增殖而延迟细胞凋亡。
Serdemetan (JNJ-26854165) Chemical Structure
CAS: 881202-45-5
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相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| KU-19-19 cell | Growth inhibition assay | Inhibition of human KU-19-19 cell growth in a cell viability assay, IC50=0.93236 μM | SANGER | ||
| H4 cell | Growth inhibition assay | Inhibition of human H4 cell growth in a cell viability assay, IC50=1.06707 μM | SANGER | ||
| KGN cell | Growth inhibition assay | Inhibition of human KGN cell growth in a cell viability assay, IC50=1.6205 μM | SANGER | ||
| 786-0 cell | Growth inhibition assay | Inhibition of human 786-0 cell growth in a cell viability assay, IC50=1.72989 μM | SANGER | ||
| 769-P cell | Growth inhibition assay | Inhibition of human 769-P cell growth in a cell viability assay, IC50=1.82224 μM | SANGER | ||
| K5 cell | Growth inhibition assay | Inhibition of human K5 cell growth in a cell viability assay, IC50=2.01624 μM | SANGER | ||
| MLMA cell | Growth inhibition assay | Inhibition of human KOSC-2 cell growth in a cell viability assay, IC50=2.03217 μM | SANGER | ||
| MLMA cell | Growth inhibition assay | Inhibition of human MLMA cell growth in a cell viability assay, IC50=2.28703 μM | SANGER | ||
| EW-7 cell | Growth inhibition assay | Inhibition of human EW-7 cell growth in a cell viability assay, IC50=2.32695 μM | SANGER | ||
| SW1088 cell | Growth inhibition assay | Inhibition of human SW1088 cell growth in a cell viability assay, IC50=2.80651 μM | SANGER | ||
| MC-IXC cell | Growth inhibition assay | Inhibition of human MC-IXC cell growth in a cell viability assay, IC50=2.87792 μM | SANGER | ||
| NCI-H2052 cell | Growth inhibition assay | Inhibition of human NCI-H2052 cell growth in a cell viability assay, IC50=3.08157 μM | SANGER | ||
| IGR-1 cell | Growth inhibition assay | Inhibition of human IGR-1 cell growth in a cell viability assay, IC50=3.12028 μM | SANGER | ||
| DSH1 cell | Growth inhibition assay | Inhibition of human DSH1 cell growth in a cell viability assay, IC50=3.24296 μM | SANGER | ||
| PA-1 cell | Growth inhibition assay | Inhibition of human PA-1 cell growth in a cell viability assay, IC50=3.30059μM | SANGER | ||
| SK-MEL-3 cell | Growth inhibition assay | Inhibition of human SK-MEL-3 cell growth in a cell viability assay, IC50=3.31207 μM | SANGER | ||
| SW900 cell | Growth inhibition assay | Inhibition of human SW900 cell growth in a cell viability assay, IC50=3.48255 μM | SANGER | ||
| CAKI-1 cell | Growth inhibition assay | Inhibition of human CAKI-1 cell growth in a cell viability assay, IC50=3.52738 μM | SANGER | ||
| ES1 cell | Growth inhibition assay | Inhibition of human ES1 cell growth in a cell viability assay, IC50=3.52897 μM | SANGER | ||
| SK-N-DZ cell | Growth inhibition assay | Inhibition of human SK-N-DZ cell growth in a cell viability assay, IC50=3.62595 μM | SANGER | ||
| RH-1 cell | Growth inhibition assay | Inhibition of human RH-1 cell growth in a cell viability assay, IC50=3.68463 μM | SANGER | ||
| ES8 cell | Growth inhibition assay | Inhibition of human ES8 cell growth in a cell viability assay, IC50=3.69702 μM | SANGER | ||
| NEC8 cell | Growth inhibition assay | Inhibition of human NEC8 cell growth in a cell viability assay, IC50=3.76982 μM | SANGER | ||
| LNCaP-Clone-FGC cell | Growth inhibition assay | Inhibition of human LNCaP-Clone-FGC cell growth in a cell viability assay, IC50=3.83536 μM | SANGER | ||
| HCE-4 cell | Growth inhibition assay | Inhibition of human HCE-4 cell growth in a cell viability assay, IC50=3.9807 μM | SANGER | ||
| U-118-MG cell | Growth inhibition assay | Inhibition of human U-118-MG cell growth in a cell viability assay, IC50=4.01066 μM | SANGER | ||
| GI-ME-N cell | Growth inhibition assay | Inhibition of human GI-ME-N cell growth in a cell viability assay, IC50=4.08796 μM | SANGER | ||
| LB1047-RCC cell | Growth inhibition assay | Inhibition of human LB1047-RCC cell growth in a cell viability assay, IC50=4.16143 μM | SANGER | ||
| HT-1080 cell | Growth inhibition assay | Inhibition of human HT-1080 cell growth in a cell viability assay, IC50=4.19921 μM | SANGER | ||
| NB69 cell | Growth inhibition assay | Inhibition of human NB69 cell growth in a cell viability assay, IC50=4.35047 μM | SANGER | ||
| NCI-H1693 cell | Growth inhibition assay | Inhibition of human NCI-H1693 cell growth in a cell viability assay, IC50=4.44895 μM | SANGER | ||
| HSC-3 cell | Growth inhibition assay | Inhibition of human HSC-3 cell growth in a cell viability assay, IC50=4.49933 μM | SANGER | ||
| MDA-MB-231 cell | Growth inhibition assay | Inhibition of human MDA-MB-231 cell growth in a cell viability assay, IC50=4.55899 μM | SANGER | ||
| HOS cell | Growth inhibition assay | Inhibition of human HOS cell growth in a cell viability assay, IC50=4.7863 μM | SANGER | ||
| BT-549 cell | Growth inhibition assay | Inhibition of human BT-549 cell growth in a cell viability assay, IC50=4.7887 μM | SANGER | ||
| NB17 cell | Growth inhibition assay | Inhibition of human NB17 cell growth in a cell viability assay, IC50=4.78976 μM | SANGER | ||
| 5637 cell | Growth inhibition assay | Inhibition of human 5637 cell growth in a cell viability assay, IC50=4.79652 μM | SANGER | ||
| OVCAR-8 cell | Growth inhibition assay | Inhibition of human OVCAR-8 cell growth in a cell viability assay, IC50=4.92436 μM | SANGER | ||
| G-402 cell | Growth inhibition assay | Inhibition of human G-402 cell growth in a cell viability assay, IC50=4.93035 μM | SANGER | ||
| BB30-HNC cell | Growth inhibition assay | Inhibition of human BB30-HNC cell growth in a cell viability assay, IC50=5.07218 μM | SANGER | ||
| HCC1806 cell | Growth inhibition assay | Inhibition of human HCC1806 cell growth in a cell viability assay, IC50=5.08339 μM | SANGER | ||
| COLO-800 cell | Growth inhibition assay | Inhibition of human COLO-800 cell growth in a cell viability assay, IC50=5.1264 μM | SANGER | ||
| FADU cell | Growth inhibition assay | Inhibition of human FADU cell growth in a cell viability assay, IC50=5.36557 μM | SANGER | ||
| NCI-H1651 cell | Growth inhibition assay | Inhibition of human NCI-H1651 cell growth in a cell viability assay, IC50=5.39409 μM | SANGER | ||
| AGS cell | Growth inhibition assay | Inhibition of human AGS cell growth in a cell viability assay, IC50=5.47711 μM | SANGER | ||
| CHP-212 cell | Growth inhibition assay | Inhibition of human CHP-212 cell growth in a cell viability assay, IC50=5.39409 μM | SANGER | ||
| YAPC cell | Growth inhibition assay | Inhibition of human YAPC cell growth in a cell viability assay, IC50=5.47711 μM | SANGER | ||
| GOTO cell | Growth inhibition assay | Inhibition of human GOTO cell growth in a cell viability assay, IC50=5.49576 μM | SANGER | ||
| KYSE-510 cell | Growth inhibition assay | Inhibition of human KYSE-510 cell growth in a cell viability assay, IC50=5.511 μM | SANGER | ||
| NCI-H2342 cell | Growth inhibition assay | Inhibition of human NCI-H2342 cell growth in a cell viability assay, IC50=5.53278 μM | SANGER | ||
| BFTC-905 cell | Growth inhibition assay | Inhibition of human BFTC-905 cell growth in a cell viability assay, IC50=5.62835 μM | SANGER | ||
| EW-16 cell | Growth inhibition assay | Inhibition of human EW-16 cell growth in a cell viability assay, IC50=5.72093 μM | SANGER | ||
| SK-MEL-30 cell | Growth inhibition assay | Inhibition of human SK-MEL-30 cell growth in a cell viability assay, IC50=5.74543 μM | SANGER | ||
| HLE cell | Growth inhibition assay | Inhibition of human HLE cell growth in a cell viability assay, IC50=5.77489 μM | SANGER | ||
| T98G cell | Growth inhibition assay | Inhibition of human T98G cell growth in a cell viability assay, IC50=5.79635 μM | SANGER | ||
| HUTU-80 cell | Growth inhibition assay | Inhibition of human HUTU-80 cell growth in a cell viability assay, IC50=5.84228 μM | SANGER | ||
| NOS-1 cell | Growth inhibition assay | Inhibition of human NOS-1 cell growth in a cell viability assay, IC50=5.94766 μM | SANGER | ||
| SW780 cell | Growth inhibition assay | Inhibition of human SW780 cell growth in a cell viability assay, IC50=5.96949 μM | SANGER | ||
| KYSE-180 cell | Growth inhibition assay | Inhibition of human KYSE-180 cell growth in a cell viability assay, IC50=5.97654 μM | SANGER | ||
| MDA-MB-361 cell | Growth inhibition assay | Inhibition of human MDA-MB-361 cell growth in a cell viability assay, IC50=5.98647 μM | SANGER | ||
| SNU-C2B cell | Growth inhibition assay | Inhibition of human SNU-C2B cell growth in a cell viability assay, IC50=6.01138 μM | SANGER | ||
| NCI-H661 cell | Growth inhibition assay | Inhibition of human NCI-H661 cell growth in a cell viability assay, IC50=6.0694 μM | SANGER | ||
| OE33 cell | Growth inhibition assay | Inhibition of human OE33 cell growth in a cell viability assay, IC50=6.14389 μM | SANGER | ||
| TYK-nu cell | Growth inhibition assay | Inhibition of human TYK-nu cell growth in a cell viability assay, IC50=6.21863 μM | SANGER | ||
| COLO-792 cell | Growth inhibition assay | Inhibition of human COLO-792 cell growth in a cell viability assay, IC50=6.25219 μM | SANGER | ||
| HEL cell | Growth inhibition assay | Inhibition of human HEL cell growth in a cell viability assay, IC50=6.2676 μM | SANGER | ||
| D-566MG cell | Growth inhibition assay | Inhibition of human D-566MG cell growth in a cell viability assay, IC50=6.33491 μM | SANGER | ||
| U031 cell | Growth inhibition assay | Inhibition of human U031 cell growth in a cell viability assay, IC50=6.41816 μM | SANGER | ||
| COR-L23 cell | Growth inhibition assay | Inhibition of human COR-L23 cell growth in a cell viability assay, IC50=6.43346 μM | SANGER | ||
| NCI-H2452 cell | Growth inhibition assay | Inhibition of human NCI-H2452 cell growth in a cell viability assay, IC50=6.52281 μM | SANGER | ||
| BB65-RCC cell | Growth inhibition assay | Inhibition of human BB65-RCC cell growth in a cell viability assay, IC50=6.6459 μM | SANGER | ||
| CAL-33 cell | Growth inhibition assay | Inhibition of human CAL-33 cell growth in a cell viability assay, IC50=6.65665 μM | SANGER | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Serdemetan (JNJ-26854165)是一种HDM2泛素连接酶拮抗剂，作用于p53野生型细胞，诱导早期凋亡，在缺乏功能性p53的细胞中，抑制细胞增殖而延迟细胞凋亡。 | |||
|---|---|---|---|---|
| 特性 | JNJ 26854165是口服生物有效性的，小分子HDM2拮抗剂，具有有效的抗肿瘤活性。 | |||
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | JNJ-26854165是新型激活p53的色胺衍生物，作为HDM2泛素连接酶拮抗剂。JNJ-26854165作用于白血病细胞系，抑制细胞生长，且诱导凋亡，作用于OCI-AML-3, MOLM-13,NALM-6和REH细胞72小时后，IC50值分别为0.24,0.33,0.32和0.44 µM。此外, JNJ-26854165作用于p53突变的细胞，加速蛋白酶调节的p21降解和抗p53对p21的转录诱导, 诱导S期延迟，且上调E2F1表达, 导致S期细胞优先凋亡。[1] JNJ-26854165是口服MDM2抑制剂，可以抑制MDM2-p53复合体与蛋白酶的相互作用，且通过与MDM2的RING域结合提高p53水平。[2]最新研究显示JNJ-26854165作用于四种人类癌细胞系:H460,A549,p53-WT-HCT116,和p53-null-HCT116，抑制无性繁殖生存。[3] | |||
|---|---|---|---|---|
| 细胞实验 | 细胞系 | OCI-AML-3,MOLM-13,NB4和U937细胞 | ||
| 浓度 | 0到10 μM | |||
| 孵育时间 | 72 小时 | |||
| 方法 | 细胞系维持在含10%热灭活胎牛血清(FCS)的RPMI 1640培养基上。急性骨髓性白血病(AML) 患者体内得到的OCI-AML-3, MOLM-13, NB4和 U937 细胞,慢性髓细胞性白血病(CML)患者体内得到的K562细胞,急性成淋巴细胞性白血病(ALL)患者体内得到的NALM-6, REH, P12-ICHIKAWA和PF-382细胞。OCI-AML-3, MOLM-13, NALM-6和 REH 细胞具有野生型p53, 然而NB4,U937,K562,P12-ICHIKAWA和PF-382细胞具有突变型p53，获得对数生长期细胞系，接种，用JNJ-26854165处理。白血病患者体内获得的白血病细胞中获得肝素外周血或骨髓样本。通过密度梯度离心纯化单核细胞，非黏着细胞悬浮在含10%FCS的RPMI 1640培养基上。正常骨髓衍生的干细胞接种在含MEM-α培养基的12孔板上，24小时后，加入AML细胞。为了研究骨髓干细胞作用于原代白血病细胞的效果，培养AML 细胞。在JNJ-26854165和 AraC的联合实验中,用0,2,5或 10 μM。JNJ-26854165 处理AML细胞系。在OCI-AML-3细胞中 JNJ-26854165与 AraC的浓度比为1:1，在其他细胞中为10:1。两种试剂同时加到细胞中，培养48小时。JNJ-26854165和Doxorubicin联用的实验中,两种试剂同时加到细胞中，培养48小时。用 0, 25, 50或 100 nM Doxorubicin处理细胞 (用0,100,200 或400 nM Doxorubicin 处理OCI-AML-3细胞和原代白血病细胞)，Doxorubicin 与JNJ-26854165 的浓度比为1:10 (在OCI-AML-3细胞和原代白血病细胞中比为1:25)。通过台酚蓝染料重复计数，测评细胞活力。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | Bcr-abl / p-Bcr-abl / p-CrkL / STAT5 / p-STAT5 / STAT3 / p-STAT3 MDM2 / p-MDM2 / p53 ABCA1 / ABCG1 / NPC1 / NPC2 / HMGcoR p53 / HDM2 / HDMX / p21 / Noxa / Puma |
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27999193 | |
| Growth inhibition assay | Cell viability |
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23820125 | |
| Immunofluorescence | p53 |
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27999193 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | JNJ-26854165按20 mg/kg剂量口服饲喂于三十六分之十七(47%)实体移植瘤和七分之五(71%) ALL移植瘤，持续5天，重复进行6周，导致EFS分布出现明显区别。[4] | |
|---|---|---|
| 动物实验 | Animal Models | 皮下注射kidney/rhabdoid肿瘤,肉瘤, 成神经细胞瘤, 和非恶性胶质瘤脑癌的雌性CB17SC scid-/-小鼠，携带神经胶质瘤的BALB/c nu/nu小鼠 |
| Dosages | ≤20 mg/kg | |
| Administration | 口服处理 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00676910 | Completed | Neoplasms |
Johnson & Johnson Pharmaceutical Research & Development L.L.C. |
November 2006 | Phase 1 |
化学信息&溶解度
| 分子量 | 328.41 | 分子式 | C21H20N4 |
| CAS号 | 881202-45-5 | SDF | Download Serdemetan (JNJ-26854165) SDF |
| Smiles | C1=CC=C2C(=C1)C(=CN2)CCNC3=CC=C(C=C3)NC4=CC=NC=C4 | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 66 mg/mL ( (200.96 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 2 mg/mL (6.08 mM) Water : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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