CAS:848695-25-0
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to off-white Solid
BIIB021 是一种 HSP90 抑制剂。
Array ( [133] => Array ( [id] => 133 [name] => Inhibitors & Antagonists & Agonists [children] => Array ( [352] => Array ( [id] => 352 [name] => Protein Tyrosine Kinase/PTK ) [350] => Array ( [id] => 350 [name] => PI3K/Akt/mTOR ) [351] => Array ( [id] => 351 [name] => Endocrinology & Hormones ) [357] => Array ( [id] => 357 [name] => Angiogenesis ) [358] => Array ( [id] => 358 [name] => HIF ) [363] => Array ( [id] => 363 [name] => Immunology & Inflammation ) [364] => Array ( [id] => 364 [name] => Stem Cells ) [365] => Array ( [id] => 365 [name] => Apoptosis ) [377] => Array ( [id] => 377 [name] => Metabolic Enzyme & Protease ) [379] => Array ( [id] => 379 [name] => Autophagy ) [380] => Array ( [id] => 380 [name] => ER Stress ) [384] => Array ( [id] => 384 [name] => Cell Cycle ) [385] => Array ( [id] => 385 [name] => Cytoskeleton ) [386] => Array ( [id] => 386 [name] => DNA Damage & DNA Repai ) [387] => Array ( [id] => 387 [name] => Epigenetics ) [388] => Array ( [id] => 388 [name] => Ubiquitin ) [389] => Array ( [id] => 389 [name] => JAK/STAT ) [390] => Array ( [id] => 390 [name] => GPCR & G Protein ) [391] => Array ( [id] => 391 [name] => Neuronal Signal Pathway ) [392] => Array ( [id] => 392 [name] => MAPK ) [393] => Array ( [id] => 393 [name] => NF-κB ) [394] => Array ( [id] => 394 [name] => Membrane Transporter & Ion Channel ) [395] => Array ( [id] => 395 [name] => TGF-β/Smad ) [396] => Array ( [id] => 396 [name] => Hippo ) [775] => Array ( [id] => 775 [name] => Antibody-drug Conjugate/ADC Related ) [122] => Array ( [id] => 122 [name] => Others ) ) [num] => 3416 ) )
>
Small Molecule Compounds >
Inhibitors & Antagonists & Agonists >
Cell Cycle >
CNF2024CAS:848695-25-0
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to off-white Solid
CAS | 848695-25-0 |
English Name | CNF2024 |
Synonyms | BIIB-021 |
Molecular Formula | C14H15ClN6O |
Molecular Weight | 318.77 |
Solubility | Soluble in DMSO |
Purity | ≥98% |
Appearance | White to off-white Solid |
Storage | Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
EC | EINECS 812-781-2 |
MDL | MFCD15528939 |
SMILES | ClC1=C2C(N(C=N2)CC3=C(C(OC)=C(C=N3)C)C)=NC(N)=N1 |
Target Point | HSP90 |
Passage | Cell Cycle;Metabolic Enzyme&Protease |
Background | BIIB021 is an HSP90 inhibitor. |
Biological Activity | BIIB021 是一种 HSP90 抑制剂,Ki 值和 EC50 值分别为 1.7 nM 和 38 nM[4]。 |
In Vitro | CNF2024比针对肾上腺皮质癌H295R的17-AAG活性高得多。 CNF2024的细胞毒活性不受NQO1或Bcl-2过表达的损失的影响,这些分子病变不会阻止客户端丢失,但仍与17-AAG的细胞杀伤减少有关。 CNF2024在17-AAG抗性细胞系(NIH-H69,MES SA Dx5,NCI-ADR-RES,Nalm6)中也有活性[4]。 CNF2024抑制霍奇金淋巴瘤细胞(KM-H2,L428,L540,L540cy,L591,L1236和DEV),IC50为0.24-0.8μM。 CNF2024显示来自健康个体的淋巴细胞的低活性。尽管有缺陷的IκB,CNF2024抑制NF-κB的组成性活性。 CNF2024诱导霍奇金淋巴瘤细胞上激活NK细胞受体NKG2D的配体表达,导致对NK细胞介导的杀伤的易感性增加[2]。CNF2024结合在Hsp90的ATP结合口袋中,干扰Hsp90伴侣功能,并导致客户蛋白质降解和肿瘤生长抑制。 CNF2024抑制肿瘤细胞(BT474,MCF-7,N87,HT29,H1650,H1299,H69和H82)增殖,IC50为0.06-0.31μM。 CNF2024诱导Hsp90客户蛋白的降解,包括HER-2,Akt和Raf-1,并且上调热休克蛋白Hsp70和Hsp27的表达[1]。 CNF2024增强HNSCCA细胞系(UM11B和JHU12)的体外放射敏感性,相应降低关键放射应答蛋白的表达,增加凋亡细胞并增强G2阻滞[3]。 |
In Vivo | CNF2024的口服给药导致许多肿瘤异种移植模型中的肿瘤生长抑制,包括N87,BT474,CWR22,U87,SKOV3和Panc-1 [1]。 CNF2024以120 mg/kg的剂量有效抑制L540cy肿瘤的生长[2]。 CNF2024显著增强JHU12异种移植物中辐射的抗肿瘤生长作用[3]。 |
Cell Experiment | 使用改良的四唑盐测定来测量IC 50。将肿瘤细胞加入96孔板中并在加入CNF2024之前繁殖24小时。将CNF2024添加到镀覆的细胞中。包含DMSO(0.03-0.003%)作为媒介物对照。孵育后,吩嗪硫酸甲酯(原料浓度1 mg/mL)和3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-四唑盐,内盐(将原液浓度2mg/mL)以1:20的比例混合,并加入到96孔板的每个孔中。还原3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-四唑鎓,内盐产生可溶性甲product产物,其分泌到培养基。温育4小时后,在490nm的波长下用分光光度法定量甲product产物。使用SOFTmaxPRO软件获取数据,100%活力定义为用3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-)染色的DMSO处理细胞的A490磺基苯基)-2H-四唑鎓,内盐(用DMSO处理的细胞的平均A490,范围为0.03-0.003%)。如下从A490值计算每个样品的活力百分比:%活力=(A490nm样品/ A490nm DMSO处理的细胞×100)。 IC 50定义为引起50%细胞活力抑制的浓度。 |
Animal Experiment | BALB/c和无胸腺小鼠在6至8周时从Harlan Sprague-Dawley获得。将小鼠保持在通气笼养系统中的灭菌笼中,其中12小时光照/ 12小时黑暗光周期,温度为21℃至23℃,相对湿度为50±5%。随意提供经辐照的颗粒状食物和高压灭菌的去离子水。通过使用单独编号的耳标识别动物。将N87肿瘤碎片(约2mm 3)皮下植入动物的右侧。在接种BT474之前,放置1.7 mg/90天释放17β-雌二醇颗粒sc CNF2024以31,62.5和125 mg/kg的剂量给予携带N87胃癌肿瘤的动物,每周一次,从周一到周五,共5天周。使用卡尺测量肿瘤尺寸,并使用椭圆球(l×w2)/ 2 = mm3的等式计算肿瘤体积,其中l和w分别表示在每次测量时收集的越来越大的尺寸。测量肿瘤体积并称重动物并每周至少两次监测毒性。使用双尾学生t检验计算P值,以评估对照组和治疗组之间肿瘤体积的差异。 |
Kinase Experiment | 对于荧光偏振竞争测量,将FITC-格尔德霉素探针(20nM)在室温下用2mM TCEP还原3小时,之后将溶液等分并储存在-80℃直至使用。将重组人Hsp90α(0.8nM)和还原的FITC-格尔德霉素(2nM)在含有20mM HEPES(pH7.4),50mM KCl,5的测定缓冲液的存在下,在室温下在96孔微量培养板中孵育3小时。 mM MgCl 2,20mM Na 2 MoO 4,2mM DTT,0.1mg/mL BGG和0.1%(v/v)CHAPS。在该预温育后,然后加入100%DMSO中的CNF2024至终浓度0.2nM至10μM(终体积100μL,2%DMSO)。将反应物在室温下温育16小时,然后在Analyst读板仪中测量荧光,激发= 485nm,发射= 535nm。高和低对照分别不含CNF2024或不含Hsp90。数据适合四参数曲线并生成IC50。 |
Data Literature Source | [1]. Lundgren,Karen.,et al. CNF2024,an orally available,fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Molecular Cancer Therapeutics (2009),8(4),921-929. [2]. B ll B,et al. Heat shock protein 90 inhibitor CNF2024 (CNF2024) depletes NF-kappaB and sensitizes Hodgkin's lymphoma cells for natural killer cell-mediated cytotoxicity. Clin Cancer Res. 2009 Aug 15;15(16):5108-16. [3]. Yin X,et al. CNF2024,a novel Hsp90 inhibitor,sensitizes head and neck squamous cell carcinoma to radiotherapy. Int J Cancer. 2010 Mar 1;126(5):1216-25. [4]. Zhang H,et al. CNF2024,a synthetic Hsp90 inhibitor,has broad application against tumors with acquired multidrug resistance. Int J Cancer. 2010 Mar 1;126(5):1226-34. |
Unit | Bottle |
Specification | 5mg 20mg |
BIIB021 是一种 HSP90 抑制剂。