BIIB021

別名: CNF2024

目錄號：S1175 Purity: 99.89%

BIIB021 (CNF2024)是一種口服有效的，全部人工合成的，小分子HSP90抑制劑，K_i和EC50分別為1.7 nM和38 nM。Phase 2.

BIIB021 Chemical Structure

CAS: 848695-25-0

規(guī)格	價(jià)格	庫存
5mg	737.1	現(xiàn)貨
25mg	2211.3	現(xiàn)貨
50mg	3333.33	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次：純度： 99.89%

99.89

BIIB021相關(guān)產(chǎn)品

相關(guān)靶點(diǎn)	HSP40 HSP70 HSP90 HSP105 HSF1	點(diǎn)擊展開
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相關(guān)化合物庫	激酶抑制劑庫血管生成相關(guān)化合物庫 TGF-beta/Smad信號通路庫細(xì)胞骨架信號通路化合物庫抗心血管疾病化合物庫	點(diǎn)擊展開

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	給藥濃度	孵育時(shí)間	活性描述	文獻(xiàn)信息(PMID)
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
點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù)

生物活性

產(chǎn)品描述

BIIB021 (CNF2024)是一種口服有效的，全部人工合成的，小分子HSP90抑制劑，K_i和EC50分別為1.7 nM和38 nM。Phase 2.

特性

BIIB021是全人工合成的口服Hsp90 抑制劑。

靶點(diǎn)

HSP90 ^[1]
(Cell-free assay)

1.7 nM(Ki)

體外研究(In Vitro)
體外研究活性	BIIB021 結(jié)合到Hsp90的ATP結(jié)合袋中, 干涉Hsp90伴侶功能, 導(dǎo)致客戶蛋白降解和腫瘤生長受抑制。BIIB021抑制腫瘤細(xì)胞 (BT474, MCF-7, N87, HT29, H1650, H1299, H69和H82) 增殖， IC50為0.06-0.31 μM。BIIB021誘導(dǎo)Hsp90客戶蛋白包括HER-2, AKT, 和Raf-1的降解，以及正向調(diào)節(jié)Hsp70 和Hsp27。^[1] BIIB021 抑制Hodgkin's 淋巴癌細(xì)胞(KM-H2, L428, L540, L540cy, L591, L1236 和DEV) ，IC50 為0.24-0.8 μM。BIIB021 作用于健康個(gè)體的淋巴細(xì)胞時(shí)活性低。BIIB021 抑制NF-κB 活性。BIIB021 誘導(dǎo)Hodgkin's 淋巴癌細(xì)胞中激活 NK細(xì)胞受體NKG2D配體的表達(dá)，導(dǎo)致對NK細(xì)胞調(diào)節(jié)的死亡敏感性上升。^[2] 在體外，BIIB021 增強(qiáng)HNSCCA 細(xì)胞系 (UM11B和JHU12)的放射敏感性，伴隨關(guān)鍵放射反應(yīng)蛋白的表達(dá)下降, 增強(qiáng)凋亡細(xì)胞和增強(qiáng)G2期捕獲。^[3]在體內(nèi)外，與17-AAG 相比，作用于腎上腺皮質(zhì)癌H295R,BIIB021更有效。BIIB021的細(xì)胞毒性不受NQO1或Bcl-2 過量表達(dá)缺失影響, 分子損傷與17-AAG降低細(xì)胞殺傷力有關(guān)。^[4] BIIB021作用于抗17-AAG細(xì)胞系(NIH-H69,MES SA Dx5,NCI-ADR-RES, Nalm6等等)也有效。^[5]
激酶實(shí)驗(yàn)	Hsp90結(jié)合實(shí)驗(yàn)
激酶實(shí)驗(yàn)	用于熒光偏振競爭測量, FITC-geldanamycin 探針 (20 nM) 和2 mM TCEP 在室溫下進(jìn)行3 小時(shí), 然后等分置于-80^oC儲存。重組人類Hsp90α (0.8 nM) 和降低的 FITC-geldanamycin (2 nM) 在含有實(shí)驗(yàn)buffer的96孔板上在室溫下溫育3 小時(shí)，實(shí)驗(yàn)buffer包含20 mM HEPES (pH 為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。預(yù)溫育后，加入溶于100% DMSO的BIIB021 ，最終濃度為0.2 nM 到10 μM (最終體積為100 μL, 2% DMSO)。反應(yīng)在室溫下進(jìn)行16小時(shí)，在485和535 nm處測定熒光值。
細(xì)胞實(shí)驗(yàn)	細(xì)胞系	BT474, MCF-7, N87, HT29, H1650, H1299, H69和H82細(xì)胞
	濃度	3到1×10³ nM
	孵育時(shí)間	5 天
	方法	使用修改的四唑鎓鹽法測定IC50值。腫瘤細(xì)胞加到96孔板上繁殖 24小時(shí)，然后加入BIIB021。對照組加入DMSO (0.03-0.003%)。吩嗪硫酸甲酯(儲存濃度為1 mg/mL) 和3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲羥苯基)-2-(4-磺苯基)-2氫-四唑, 內(nèi)鹽 (儲存濃度為2 mg/mL) 按1:20混合，加到96孔板的每孔中，溫育。3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲羥苯基)-2-(4-磺苯基)-2氫-四唑, 內(nèi)鹽的降低，導(dǎo)致可溶性甲臢分泌到培養(yǎng)基中。溫育4小時(shí), 在490納米處使用分光光度計(jì)測量甲臢。使用SOFTmaxPRO軟件獲得數(shù)據(jù), 100% 生存力定義為用DMSO處理的細(xì)胞A490，用 3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲羥苯基)-2-(4-磺苯基)-2氫-四唑, 內(nèi)鹽(用DMSO處理細(xì)胞的平均A490 為0.03-0.003%)染色通過A₄₉₀ 值計(jì)算每個(gè)樣本存活百分?jǐn)?shù)，計(jì)算按如下:存活率（%） = (A_{490 nm}樣本/ A_{490 nm}DMSO處理的細(xì)胞 × 100)。

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	BIIB021口服處理多種移植瘤模型（包括N87, BT474, CWR22, U87, SKOV3和 Panc-1）導(dǎo)致腫瘤生長受抑制。^[1] BIIB021按120 mg/kg劑量處理 L540cy 腫瘤，有效抑制腫瘤的生長。^[2] BIIB021 作用于JHU12移植瘤，明顯增強(qiáng)抗腫瘤生長功效。^[3]
動物實(shí)驗(yàn)	Animal Models	BALB/c和無胸腺鼠中的N87, BT474, CWR22, U87, SKOV3和 Panc-1腫瘤模型
	Dosages	31, 62.5,和125 mg/kg
	Administration	每天口服處理一次

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗(yàn)信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

參考文獻(xiàn)
https://pubmed.ncbi.nlm.nih.gov/19372565/ https://pubmed.ncbi.nlm.nih.gov/19671844/ https://pubmed.ncbi.nlm.nih.gov/19662650/ https://pubmed.ncbi.nlm.nih.gov/19676042/ + 展開

參考文獻(xiàn)

https://pubmed.ncbi.nlm.nih.gov/19372565/
https://pubmed.ncbi.nlm.nih.gov/19671844/
https://pubmed.ncbi.nlm.nih.gov/19662650/

https://pubmed.ncbi.nlm.nih.gov/19676042/

+ 展開

化學(xué)信息&溶解度

分子量	318.76	分子式	C₁₄H₁₅ClN₆O
CAS號	848695-25-0	SDF	Download BIIB021 SDF
Smiles	CC1=CN=C(C(=C1OC)C)CN2C=NC3=C2N=C(N=C3Cl)N
儲存條件(自收到貨起)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復(fù)凍融！	1年-80°C溶于溶劑
儲存條件(自收到貨起)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復(fù)凍融！	1個(gè)月-20°C溶于溶劑

體外溶解度
批次：

DMSO : 64 mg/mL ( (200.77 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 12 mg/mL (37.64 mM)

Water : Insoluble

DMSO : 64 mg/mL ( (200.77 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 2 mg/mL (6.27 mM)

Water : Insoluble

DMSO : 64 mg/mL ( (200.77 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 2 mg/mL (6.27 mM)

Water : Insoluble

DMSO : 64 mg/mL ( (200.77 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 2 mg/mL (6.27 mM)

Water : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解配方批次：現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑				動物體內(nèi)配方計(jì)算器
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
澄清溶液	30%propylene glycol 1 5%Tween80 2 65%D5W 該配方已經(jīng)過Selleck實(shí)驗(yàn)室實(shí)測。如果上述溶解方案不能滿足您的需求，可聯(lián)系Selleck銷售提供定制化測試。	30.000mg/ml (94.11mM)	以 1 mL 工作液為例，取300μL100mg/ml的澄清propylene glycol儲備液加到50μL Tween 80中，混合均勻使其澄清；然后繼續(xù)加入650μL D5W定容至 1 mL。工作液請現(xiàn)配現(xiàn)用！
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計(jì)算器分子量計(jì)算器

動物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過程中的損耗，建議多配一只動物的藥量）

給藥劑量 mg/kg 動物平均體重 g 每只動物給藥體積 μL 動物數(shù)量只

第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH₂O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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* 必填項(xiàng)

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

BIIB021

產(chǎn)品質(zhì)控

BIIB021相關(guān)產(chǎn)品

相關(guān)信號通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

生物活性

化學(xué)信息&溶解度

實(shí)驗(yàn)計(jì)算

技術(shù)支持