BIIB021
别名: CNF2024
BIIB021 (CNF2024)是一种口服有效的，全部人工合成的，小分子HSP90抑制剂，Ki和EC50分别为1.7 nM和38 nM。Phase 2.
BIIB021 Chemical Structure
CAS: 848695-25-0
产品质控
批次：
纯度：
99.89%
99.89
BIIB021相关产品
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 |
|---|---|---|---|---|---|
| NCI-H295 | Cytotoxicity assay | 120 mg/kg | 5 days | Cytotoxicity against human NCI-H295 cells overexpressing PGP xenografted in athymic mouse assessed as inhibition of tumor growth at 120 mg/kg, po qd for 5 days per week for 4 weeks | 22938030 |
| HeLa | Function assay | 10 uM | 6 hrs | Inhibition of HSP90 in human HeLa cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method | 28816449 |
| HeLa | Function assay | 10 uM | 6 hrs | Inhibition of HSP90 in human HeLa cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method | 28816449 |
| HeLa | Function assay | 10 uM | 6 hrs | Inhibition of HSP90 in human HeLa cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method | 28816449 |
| PC3 | Function assay | 10 uM | 6 hrs | Inhibition of HSP90 in human PC3 cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method | 28816449 |
| PC3 | Function assay | 10 uM | 6 hrs | Inhibition of HSP90 in human PC3 cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method | 28816449 |
| PC3 | Function assay | 10 uM | 6 hrs | Inhibition of HSP90 in human PC3 cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method | 28816449 |
| HL60 | Function assay | 1 uM | 24 hrs | Inhibition of HSP90 in human HL60 cells assessed as induction of HSP70 expression at 1 uM after 24 hrs by Western blot analysis | 29567459 |
| HL60 | Function assay | 1 uM | 24 hrs | Inhibition of HSP90 in human HL60 cells assessed as downregulation of phosphorylated Akt expression at 1 uM after 24 hrs by Western blot analysis | 29567459 |
| HL60 | Function assay | 1 uM | 24 hrs | Inhibition of HSP90 in human HL60 cells assessed as downregulation of phosphorylated STAT3 expression at 1 uM after 24 hrs by Western blot analysis | 29567459 |
| HL60 | Function assay | 1 uM | 24 hrs | Inhibition of HDAC in human HL60 cells assessed as upregulation of acetyl-alpha-tubulin levels at 1 uM after 24 hrs by Western blot analysis | 29567459 |
| HL60 | Function assay | 1 uM | 24 hrs | Inhibition of HDAC in human HL60 cells assessed as upregulation of acetylated histone H3 levels at 1 uM after 24 hrs by Western blot analysis | 29567459 |
| Sf9 | Function assay | 3 hrs | Binding affinity to human N-terminal polyHis-tagged HSP90alpha (D9 to E236) alpha-helix conformation expressed in insect sf9 cells after 3 hrs by fluorescence polarization assay, Ki=0.002μM | 24332488 | |
| Sf9 | Function assay | 3 hrs | Binding affinity to human N-terminal polyHis-tagged HSP90beta (D9 to E236) expressed in insect sf9 cells after 3 hrs by fluorescence polarization assay, Ki=0.004μM | 24332488 | |
| NCI-H1299 | Function assay | 12 hrs | Reduction in oxygen consumption rate in human NCI-H1299 cells incubated for 12 hrs | 25383915 | |
| HCT116 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HCT116 cells after 48 hrs by sulforhodamine B assay, GI50=0.15μM | 29567459 | |
| A549 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human A549 cells after 48 hrs by sulforhodamine B assay, GI50=0.33μM | 29567459 | |
| NCI-H1975 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human NCI-H1975 cells after 48 hrs by sulforhodamine B assay, GI50=0.38μM | 29567459 | |
| HL60 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HL60 cells after 48 hrs by sulforhodamine B assay, GI50=0.59μM | 29567459 | |
| MCF7 | Function assay | Inhibition of HSP90alpha in human MCF7 cells assessed as degradation of Her-2, EC50=0.038μM | 22938030 | ||
| BT474 | Function assay | Binding affinity to Hsp90 nucleotide binding domain in human BT474 cells, IC50=0.14μM | 20608738 | ||
| MCF7 | Function assay | Inhibition of HSP90-mediated client protein HER2 degradation in human MCF7 cells, IC50=0.038μM | 20055425 | ||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| MCF7 | Antiproliferative assay | Antiproliferative activity against human MCF7 cells, IC50=0.31μM | 31663736 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | BIIB021 (CNF2024)是一种口服有效的，全部人工合成的，小分子HSP90抑制剂，Ki和EC50分别为1.7 nM和38 nM。Phase 2. | ||
|---|---|---|---|
| 特性 | BIIB021是全人工合成的口服Hsp90 抑制剂。 | ||
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | BIIB021 结合到Hsp90的ATP结合袋中, 干涉Hsp90伴侣功能, 导致客户蛋白降解和肿瘤生长受抑制。BIIB021抑制肿瘤细胞 (BT474, MCF-7, N87, HT29, H1650, H1299, H69和H82) 增殖， IC50为0.06-0.31 μM。BIIB021诱导Hsp90客户蛋白包括HER-2, AKT, 和Raf-1的降解，以及 正向调节Hsp70 和Hsp27。[1] BIIB021 抑制Hodgkin's 淋巴癌细胞(KM-H2, L428, L540, L540cy, L591, L1236 和DEV) ，IC50 为0.24-0.8 μM。BIIB021 作用于健康个体的淋巴细胞时活性低。BIIB021 抑制NF-κB 活性。BIIB021 诱导Hodgkin's 淋巴癌细胞中激活 NK细胞受体NKG2D配体的表达，导致对NK细胞调节的死亡敏感性上升。[2] 在体外，BIIB021 增强HNSCCA 细胞系 (UM11B和JHU12)的放射敏感性，伴随关键放射反应蛋白的表达下降, 增强凋亡细胞和增强G2期捕获。[3]在体内外，与17-AAG 相比，作用于肾上腺皮质癌H295R,BIIB021更有效。BIIB021的细胞毒性不受NQO1或Bcl-2 过量表达缺失影响, 分子损伤与17-AAG降低细胞杀伤力有关。[4] BIIB021作用于抗17-AAG细胞系(NIH-H69,MES SA Dx5,NCI-ADR-RES, Nalm6等等)也有效。[5] | |||
|---|---|---|---|---|
| 激酶实验 | Hsp90结合实验 | |||
| 用于荧光偏振竞争测量, FITC-geldanamycin 探针 (20 nM) 和2 mM TCEP 在室温下 进行3 小时, 然后等分置于-80oC储存。 重组人类Hsp90α (0.8 nM) 和降低的 FITC-geldanamycin (2 nM) 在 含有实验buffer的96孔板上 在室温下温育3 小时，实验buffer包含20 mM HEPES (pH 为7.4), 50 mM KCl, 5 mM MgCl2, 20 mM Na2MoO4, 2 mM DTT, 0.1 mg/mL BGG,和0.1% (v/v) CHAPS。预温育后，加入溶于100% DMSO的BIIB021 ，最终浓度为0.2 nM 到10 μM (最终体积为100 μL, 2% DMSO)。反应在室温下进行16小时，在485和535 nm处测定荧光值。 | ||||
| 细胞实验 | 细胞系 | BT474, MCF-7, N87, HT29, H1650, H1299, H69和H82细胞 | ||
| 浓度 | 3到1×103 nM | |||
| 孵育时间 | 5 天 | |||
| 方法 | 使用修改的四唑鎓盐法测定IC50值。肿瘤细胞加到96孔板上繁殖 24小时，然后加入BIIB021。对照组加入DMSO (0.03-0.003%)。吩嗪硫酸甲酯(储存浓度为1 mg/mL) 和3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲羟苯基)-2-(4-磺苯基)-2氢-四唑, 内盐 (储存浓度为2 mg/mL) 按1:20混合，加到96孔板的每孔中，温育。3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲羟苯基)-2-(4-磺苯基)-2氢-四唑, 内盐的降低， 导致可溶性甲臢分泌到培养基中。温育4小时, 在490纳米处使用分光光度计测量甲臢。使用SOFTmaxPRO软件获得数据, 100% 生存力定义为用DMSO处理的细胞A490，用 3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲羟苯基)-2-(4-磺苯基)-2氢-四唑, 内盐(用DMSO处理细胞的平均A490 为0.03-0.003%)染色通过A490 值计算每个样本存活百分数，计算按如下:存活率（%） = (A490 nm样本/ A490 nmDMSO处理的细胞 × 100)。 | |||
| 体内研究(In Vivo) | ||
| 体内研究活性 | BIIB021口服处理多种移植瘤模型（包括N87, BT474, CWR22, U87, SKOV3和 Panc-1）导致肿瘤生长受抑制。[1] BIIB021按120 mg/kg剂量处理 L540cy 肿瘤，有效抑制肿瘤的生长。[2] BIIB021 作用于JHU12移植瘤，明显增强抗肿瘤生长功效。[3] | |
|---|---|---|
| 动物实验 | Animal Models | BALB/c和无胸腺鼠中的N87, BT474, CWR22, U87, SKOV3和 Panc-1肿瘤模型 |
| Dosages | 31, 62.5,和125 mg/kg | |
| Administration | 每天口服处理一次 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01017198 | Completed | Advanced Solid Tumors |
Biogen |
November 2009 | Phase 1 |
| NCT01004081 | Completed | Breast Cancer |
Biogen |
November 2009 | Phase 2 |
| NCT00618735 | Completed | Advanced Solid Tumors |
Biogen |
February 2008 | Phase 1 |
| NCT00618319 | Completed | GIST |
Biogen |
February 2008 | Phase 2 |
化学信息&溶解度
| 分子量 | 318.76 | 分子式 | C14H15ClN6O |
| CAS号 | 848695-25-0 | SDF | Download BIIB021 SDF |
| Smiles | CC1=CN=C(C(=C1OC)C)CN2C=NC3=C2N=C(N=C3Cl)N | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 64 mg/mL ( (200.77 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 12 mg/mL (37.64 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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