AT7519

别名: AT7519M

目录号：S1524 Purity: 99.9%

AT7519 是多种CDK抑制剂，作用于CDK1， 2， 4， 6和9时，IC50为10-210 nM，对CDK3作用效果稍弱，对CDK7几乎没有抑制活性。AT7519 也可抑制GSK3β的磷酸化。AT7519 可诱导凋亡。Phase 2。

AT7519 Chemical Structure

CAS: 844442-38-2

规格	价格	库存
10mM (1mL in DMSO)	1405.32	现货
5mg	903.68	现货
25mg	3016.98	现货
更大包装有超大折扣
400-668-6834 info@selleck.cn

产品质控

批次： S152402 DMSO]25 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false 纯度： 99.9%

99.9

AT7519相关产品

相关靶点	CDK1 CDK2 CDK3 CDK4 CDK5 CDK6 CDK7 CDK9 CLK Cdc CDK8 CDK12 CDK13 CDK19 CDK11 CDK/cyclin complexes	点击展开
相关产品	Ro-3306 Dinaciclib Roscovitine Flavopiridol (Alvocidib) SNS-032 (BMS-387032) Flavopiridol (Alvocidib) HCl LDC000067 PHA-767491 HCl THZ1 2HCl XL413 JNJ-7706621 AZD5438 Purvalanol A Milciclib BS-181 HCl K03861 (AUZ454) PHA-793887 BMS-265246 AT7519 HCl AZD4573 MSC2530818 Riviciclib hydrochloride (P276-00) CVT-313 TG003 Kenpaullone R547 Atuveciclib (BAY-1143572) YKL-5-124 LDC4297 Enitociclib (BAY 1251152) PF-06873600 Wogonin SU9516 SEL120 (SEL120-34A) hydrochloride THZ531 Senexin A Samuraciclib (ICEC0942) hydrochloride LY2857785 Cyclin B1 Rabbit Recombinant mAb ON123300 CDK2-IN-73 (CDK2-IN-4) NU2058 BRD6989 HLM006474 AS2863619 CDKI-73 MC180295 ML167 Simurosertib Simurosertib NSC95397 NU6027	点击展开
相关化合物库	激酶抑制剂库 PI3K/Akt 抑制剂库 MAPK抑制剂库 DNA损伤/ DNA修复化合物库细胞周期化合物库	点击展开

细胞实验数据示例

细胞系	实验类型	孵育时间	活性描述	文献信息
A2780	Antiproliferative assay	72 hrs	Antiproliferative activity against human A2780 cells assessed as cell viability after 72 hrs by alamar blue assay, IC50=0.35μM	18656911
HCT116	Antiproliferative assay	72 hrs	Antiproliferative activity against human HCT116 cells assessed as cell viability after 72 hrs by alamar blue assay, IC50=0.082μM	18656911
MRC5	Antiproliferative assay	72 hrs	Antiproliferative activity against human MRC5 cells assessed as cell viability after 72 hrs by alamar blue assay, IC50=0.98μM	18656911
HCT116	Cytotoxicity assay	72 hrs	Cytotoxicity against human HCT116 cells assessed as growth inhibition after 72 hrs by Alamar blue assay, IC50=0.08μM	26115571
MIAPaCa2	Antiproliferative assay	72 hrs	Antiproliferative activity against human MIAPaCa2 cells after 72 hrs by prestoblue assay, IC50=0.411μM	30343954
AsPC1	Antiproliferative assay	72 hrs	Antiproliferative activity against human AsPC1 cells after 72 hrs by prestoblue assay, IC50=0.533μM	30343954
SUIT2	Antiproliferative assay	72 hrs	Antiproliferative activity against human SUIT2 cells after 72 hrs by prestoblue assay, IC50=0.557μM	30343954
BxPC3	Antiproliferative assay	72 hrs	Antiproliferative activity against human BxPC3 cells after 72 hrs by prestoblue assay, IC50=0.64μM	30343954
S2-013	Antiproliferative assay	72 hrs	Antiproliferative activity against human S2-013 cells after 72 hrs by prestoblue assay, IC50=2.77μM	30343954
Sf21	Function assay	2 hrs	Inhibition of recombinant full-length human C-terminal His6-tagged CDK1/human full-length N-terminal GST-tagged Cyclin B expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate measured after 2 hrs in presence of gamma[32P] ATP b, IC50=0.21μM	30543440
HCT116	Antiproliferative assay	72 hrs	Antiproliferative activity against human HCT116 cells assessed as reduction in cell viability after 72 hrs by cell titer glo-based luminescence assay, IC50=0.132μM	31175010
HCT116	Function assay		Inhibition of CDK1 in human HCT116 cells assessed as PP1-alpha(Thr320) phosphorylation	18656911
HCT116	Function assay		Inhibition of CDK2 in human HCT116 cells assessed as Rb(Thr321) phosphorylation	18656911
HCT116	Function assay		Inhibition of CDK2 in human HCT116 cells assessed as NPM(Thr199) phosphorylation	18656911
Sf21	Function assay		Inhibition of recombinant human full length N-terminal His6-tagged CDK5/N-terminal GST-tagged p25 expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.018μM	27171036
Sf21	Function assay		Inhibition of human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin A expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.044μM	27171036
sf cells	Function assay		Inhibition of recombinant human N-terminal GST-tagged CDK4/cyclin D1 expressed in baculovirus infected sf cells, Ki=0.067μM	27171036
Sf21	Function assay		Inhibition of recombinant human full length C-terminal His6-tagged CDK9/cyclin T1 expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate, Ki<0.1μM	27171036
Sf21	Function assay		Inhibition of human full length C-terminal His6-tagged CDK1/N-terminal GST-tagged cyclin B expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.19μM	27171036
Sf21	Function assay		Inhibition of recombinant human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin E expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.51μM	27171036
Sf21	Function assay		Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide, Ki=2.8μM	27171036
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
HEI-OC1	Function assay		Protection against cisplatin-induced cell death in neonatal mouse HEI-OC1 cells assessed as reduction in caspase-3/7 activity, EC50=0.38μM	30091915
Sf21	Function assay		Inhibition of recombinant human full-length C-terminal His6-tagged CDK9/human full-length untagged cyclin T1 expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate, IC50<0.01μM	30543440
Sf21	Function assay		Inhibition of recombinant human full-length C-terminal His6-tagged CDK3/full-length human N-terminal GST-tagged Cyclin E expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, IC50=0.36μM	30543440
Sf21	Function assay		Inhibition of recombinant human C-terminal His6-tagged full length CDK7/untagged recombinant full length human Cyclin H/N-terminal GST-tagged recombinant full length human MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 peptide as subs, IC50=2.4μM	30543440
点击查看更多细胞系数据

生物活性

产品描述

靶点

CDK9/CyclinT ^[1] (Cell-free assay)	CDK5/p35 ^[1] (Cell-free assay)	CDK2/CyclinA ^[1] (Cell-free assay)	GSK-3β ^[1] (Cell-free assay)	CDK4/CyclinD1 ^[1] (Cell-free assay)	点击更多
<10 nM	13 nM	47 nM	89 nM	100 nM	点击更多

体外研究(In Vitro)
体外研究活性	AT7519是ATP竞争性CDK 抑制剂，作用于CDK1 时K_i值为38 nM。 AT7519作用于所有非CDK激酶（除了GSK3β，IC50=89 nM）没有抑制活性。AT7519作用于多种人类肿瘤细胞系，显示有效的抗增殖活性，IC50值从作用于MCF-7的40 nM到作用于 SW620 的940 nM ，与抑制CDK1和 CDK2一致。^[1] AT7519作用于多发性骨髓瘤(MM)细胞系48小时，诱导剂量依赖性毒性IC50值从 0.5到2 μM，最敏感细胞系为MM.1S (0.5 μM)和U266 (0.5 μM) ，最抵抗细胞为MM.1R (>2 μM), 但是作用于外周血单个核细胞(PBMNC)不会诱导毒性。AT7519部分克服由 IL6 和IGF-1引起的增殖优势，且保护骨髓基质细胞 (BMSCs)。AT7519 诱导RNA pol II CTD 在serine 2 和serine 5 位点快速去磷酸化, 且作用于MM 细胞通过产生毒性而抑制部分转录。AT7519通过下调GSK-3β磷酸化而诱导 GSK-3β激活，也因为 AT7519诱导凋亡，但是不抑制转录。^[2]
激酶实验	体外激酶实验
激酶实验	辐射滤波器结合格板上进行CDK1,CDK2和GSK3-β激酶实验。在DELFIA格式板上测定CDK5，在ELISA格式板上测定CDKs 4和 6。为了测定CDKs 1和2,相关的CDK 和0.12 μg/mL组蛋白H1在20 mM MOPS, pH 7.2, 25 mM β-甘油磷酸盐, 5 mM EDTA, 15 mM MgCl₂, 1 mM原钒酸钠, 1 mM DTT, 0.1 mg/mL BSA, 45 μM ATP (0.78 Ci/mmol)和不同浓度AT7519的混合物中分别温育2或4小时。测定 GSK3-β,相关的酶和 5 μM糖原合酶肽2在10 mM MOPS pH 7.0, 0.1 mg/mL BSA, 0.001% Brij-35, 0.5% 甘油, 0.2 mM EDTA, 10 mM MgCl₂, 0.01% β-巯基乙醇, 15 μM ATP (2.31 Ci/mmol) 和不同浓度AT7519 的混合物温育3小时。加入过量正磷酸终止反应，使用Millipore MAPH滤板过滤。然后冲洗板，加入闪烁剂，在 Packard TopCount上通过测定闪烁数而测量放射性。为了测定CDK5, CDK5/p35 和 1μM 生物素化的组蛋白H1肽段(生物素-PKTPKKAKKL) 在25 mM Tris-HCl, pH 7.5, 2.5 mM MgCl₂, 0.025% Brij-35, 0.1 mg/mL BSA, 1 mM DTT, 15 μM ATP 和不同浓度AT7519的混合物温育30分钟。使用EDTA终止反应,转移到 Neutravidin包被的板上，通过兔磷酸-cdk1 底物单抗和DELFIA Eu-标记的二抗抗兔 IgG，使用时间分辨荧光测定λex=335nm,λem=620nm处荧光值，而量化磷酸化底物。为了测定CDK 4和6,用 GST- pRb769-921包被板，然后用Superblock阻断。CDK4或6在15 mM MgCl₂, 50 mM HEPES, pH 7.4, 1 mM DTT, 1 mM EGTA, pH 8.0, 0.02% Triton X-100, 2.5% DMSO 和不同浓度AT7519混合物中温育，加入 ATP开始反应。30分钟后，加入 0.5 M EDTA pH 8.0终止反应。冲洗板，和一抗温育1小时，然后在 Superblock上稀释，随后用碱性磷酸酶链接抗兔二抗再处理1小时。使用Attophos系统进行板显影，然后在Spectramax Gemini计数板上读取荧光值。使用GraphPad Prism 软件从复制曲线中计算IC50 值。
细胞实验	细胞系	MM.1S, MM.1R, RPMI8226, U266, RPMI8266, RPMI-Dox40, OPM1 细胞,原代 MM细胞和 PBMNCs
	浓度	溶于DMSO，浓度为 10 mM, 终浓度为 0.25-4 μM
	孵育时间	24或48小时
	方法	37^oC下不同浓度AT7519处理细胞24或48小时。通过测量MTT染料吸光度而测定细胞活性。通过测定摄入的³H胸腺嘧啶(³H-TdR)而测定DNA合成。使用Annexin V/PI染色测评凋亡。细胞是凋亡百分数是早期凋亡数(Annexin V-阳性细胞 )和晚期凋亡数 (Annexin V-阳性和PI-阳性细胞)总和。
实验图片	检测方法	检测指标	实验图片	PMID
	Growth inhibition assay	Cell viability		20101221
	Western blot	CDK1 / CDK2 / CDK4 / Cyclin B1 / Cyclin E / CDK9 / CDK5 / CDK6 / Cyclin D1 / Cyclin A		20101221

体内研究(In Vivo)
体内研究活性	AT7519 按9.1 mg/kg剂量作用于 HCT116 和HT29 结肠癌移植瘤模型，每天两次，引起早期和晚期肿瘤衰退。^[1] AT7519按 15 mg/kg 剂量作用于携带人类MM移植瘤的小鼠模型，抑制肿瘤生长，这和提高的caspase 3激活相关。^[2]
动物实验	Animal Models	皮下注射MM.1S细胞的雄性SCID小鼠
	Dosages	15 mg/kg/day
	Administration	腹腔注射

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT01183949	Completed	Multiple Myeloma	Astex Pharmaceuticals Inc.\|Multiple Myeloma Research Consortium	November 2010	Phase 1\|Phase 2

参考文献
[1] Squires MS, et al. Mol Cancer Ther, 2009, 8(2), 324-332. [2] Santo L, et al. Oncogene, 2010, 29(16), 2325-2336.

参考文献

化学信息&溶解度

分子量	382.24	分子式	C₁₆H₁₇Cl₂N₅O₂
CAS号	844442-38-2	SDF	Download AT7519 SDF
Smiles	C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

体外溶解度
批次：

DMSO : 25 mg/mL ( (65.4 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩尔浓度计算器

体内溶解度
批次：

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

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

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）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

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。

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

* 必填项

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):