2. Cell Cycle/DNA Damage
  3. CDK
  4. AG-012986 dihydrochloride

AG-012986 (dihydrochloride) 是一种泛 CDK 抑制剂，其针对 CDK1 的 Ki 值为 44 nM，针对 CDK4 的 Ki 值为 9.2 nM，针对 CDK2 的 Ki 值为 94 nM；针对 CDK5 的 IC50 值为 22 nM，针对 CDK9 的 IC50 值为 4 nM。AG-012986 (dihydrochloride) 通过靶向 p38 丝裂原活化蛋白激酶 (MAPK) 通路中的上游激酶并损害细胞存活，从而诱导 T 细胞凋亡 (apoptosis)。AG-012986 (dihydrochloride) 可诱导细胞周期阻滞、视网膜母细胞瘤蛋白低磷酸化，并降低 Ki-67 的表达。AG-012986 (dihydrochloride) 可在肿瘤细胞中发挥抗增殖活性，在人源异种移植模型中展现抗肿瘤功效，同时会引发视网膜毒性、外周神经毒性以及免疫细胞毒性。AG-012986 (dihydrochloride) 可用于结肠癌、非小细胞肺癌、肺癌、乳腺癌、卵巢肿瘤、胰腺癌、骨肉瘤、淋巴瘤、白血病及视网膜毒性的相关研究。

MCE 的所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务

AG-012986 dihydrochloride

AG-012986 dihydrochloride Chemical Structure

CAS No. : 486414-32-8

1.  客户无需承担相应的运输费用。

2.  同一机构（单位）同一产品试用装仅限申领一次，同一机构（单位）一年内

     可免费申领三个不同产品的试用装。

3.  试用装只面向终端客户。

规格 是否有货
50 mg   询价  
100 mg   询价  
250 mg   询价  

* Please select Quantity before adding items.

Customer Review

AG-012986 dihydrochloride 相关抗体

Top Publications Citing Use of Products

查看 CDK 亚型特异性产品:

查看所有亚型
CDK1 CDK2 CDK3 CDK4 CDK5 CDK6 CDK7 CDK8 CDK9 CDK11 CDK12 CDK13 CDK14 CDK16 CDK19 CDC CLK Pho85 CDK10 CDK15 CDK17 CDK18 CDK20 PITSLRE

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

AG-012986 (dihydrochloride) is a pan-CDK inhibitor with Ki values of 44 nM (CDK1), 9.2 nM (CDK4), 94 nM (CDK2), and IC50 values of 22 nM (CDK5), 4 nM (CDK9). AG-012986 (dihydrochloride) causes apoptosis of T-cells by targeting upstream kinases in the p38 Mitogen-activated protein kinase (MAPK) pathway and impairing cellular survival. AG-012986 (dihydrochloride) induces cell cycle arrest, retinoblastoma protein hypophosphorylation, and reduces Ki-67 expression. AG-012986 (dihydrochloride) exerts antiproliferative activity in tumor cells, demonstrates antitumor efficacy in human xenograft models, and causes retinal and peripheral neurotoxicity, plus immune cell toxicity. AG-012986 (dihydrochloride) can be used for the research of colon carcinoma, non-small cell lung carcinoma, lung carcinoma, breast carcinoma, ovarian tumor, pancreatic carcinoma, osteosarcoma, lymphoma, leukemia, retinotoxicity[1][2][3][4].
IC50 & Target[1]

CDK1

44 nM (Ki)

CDK2

94 nM (Ki)

CDK3/Cyclin E

46 nM (Ki)

Cdk4/cyclin D3

9.2 nM (Ki)

CDK5/p35

22 nM (IC50)

CDK7/cyclin H

0 nM (Ki)

CDK9/CycT1

4 nM (IC50)

体外研究
(In Vitro)

AG-012986 (dihydrochloride) 是一种强效、选择性泛 CDK 抑制剂，对 CDK4/细胞周期蛋白 D3 (Ki = 9.2 nmol/L)、CDK1/细胞周期蛋白 B (Ki = 44 nmol/L)、CDK2/细胞周期蛋白 A (Ki = 94 nmol/L)、CDK9/细胞周期蛋白 T (IC50 = 4 nmol/L) 和 CDK5/p35 (IC50 = 22 nmol/L) 具有纳摩尔级活性[1]。
AG-012986 (dihydrochloride) (0.837-2.44 μmol/L) 对非激酶靶点的脱靶活性有限，在微摩尔浓度下与 L 型钙离子通道、5-羟色胺转运体和组胺 H3 受体存在功能性相互作用[1]。
AG-012986 (dihydrochloride) (72 小时) 可强效抑制 18 种人肿瘤细胞系的增殖，平均 IC50 为 120 nmol/L，且其中 13 种细胞系的 IC50 值＜100 nmol/L，该作用与 p53 和 Rb 状态无关[1]。
AG-012986 (dihydrochloride) (60-240 nM；8-24 小时) 在处理 24 小时后可诱导人结肠癌细胞 HCT116 中 Rb Ser795 发生剂量依赖性低磷酸化，在>120 nM 时效应达到最大，但处理 8 小时后仅表现出极微弱的作用[1]。
AG-012986 (dihydrochloride) (30 nM-1 μM；8-24 小时) 可在处理 24 小时后，于 30 至 120 nM 浓度下诱导人结肠癌细胞 HCT116 发生 G1 期阻滞，在≥240 nM 浓度下诱导其发生 G2-M 期阻滞，但暴露时长<8 h 时不会诱导细胞周期阻滞[1]。
AG-012986 (dihydrochloride) (30-240 nM；8-24 小时) 可诱导人结肠癌细胞 HCT116 发生凋亡，处理 24 小时后的 IC50 约为 160 nM，但处理 8 小时后无凋亡效应[1]。
AG-012986 (dihydrochloride) (10-1000 nM；8-320 小时) 在人结肠癌细胞 SW620 中表现出时间依赖性细胞毒性：作用 8 小时后活性极低，24 小时后呈现中等活性 (IC50 = 300 nmol/L)，作用 ≥72 小时后则具有显著细胞毒性 (IC50 <100 nmol/L)[1]。
AG-012986 (dihydrochloride) 在无细胞 KINOMEscan 分析中表现出对多种 CDK 亚型的结合抑制作用，对 CDK11、CDK16 和 CDK17 的 IC50 值与无神经毒性的 NVP-2 相近[2]。
AG-012986 (dihydrochloride) (200-500 nM；24 小时) 可在人 MIO-M1 Müller 细胞中诱导剂量依赖性细胞毒性，孵育 24 小时后，200 nM 浓度下可观察到细胞活力显著下降、细胞死亡增加，500 nM 浓度下作用效果达到峰值[2]。
AG-012986 (dihydrochloride) (250 nM；16 小时) 可诱导原代人外周血单个核细胞 (PBMCs) 快速发生凋亡/坏死，80%的细胞呈现 PI/Annexin-V 双阳性[3]。
AG-012986 (dihydrochloride) (50 nM-1 μM；8-48 h) 可在体外以剂量依赖方式激活人原代 PBMC 中的 caspase-3/7，在 50 nM、200 nM 或 1 μM 处理后 16-24 h 达到活性峰值[3]。
AG-012986 (dihydrochloride) (50 nM-200 nM；8 小时) 可诱导原代人外周血单核细胞 (PBMCs) 中 caspase-3 和 PARP 的裂解，在以 50 nM 或 200 nM 处理 8 小时后，证实其可引发 caspase 介导的细胞凋亡[3]。
AG-012986 (dihydrochloride) (10 nM-500 nM；16 小时) 在以 ATP 含量降低和 caspase-3/7 活性升高为检测指标的实验中对原代人 PBMC 的细胞毒性高于星形孢菌素[3]。
AG-012986 (dihydrochloride) (50 nM-250 nM；20 分钟) 的毒性特征会因 T 细胞的急性刺激而改变[3]。

AG-012986 (dihydrochloride) (20 nM-500 nM) 可抑制经其预处理并经 24 小时 α-CD3 抗体刺激的纯化原代人 T 细胞中由 α-CD3 诱导的增殖；然而，α-CD3 刺激使得这种抗增殖活性与 AG-012986 诱导的毒性相分离[3]。

AG-012986 (dihydrochloride) (20 nM-500 nM；48 小时) 可呈剂量依赖性抑制纯化的原代人 T 细胞中 α-CD3 诱导的 IL-2 产生，20 nM 浓度下观察到 IL-2 产生量降低至原来的 1/5[3]。
AG-012986 (dihydrochloride) (50 nM-250 nM；20 分钟预处理) 可抑制经 50 nM 或 250 nM 预处理 20 分钟、随后在有或无刺激条件下孵育 16 小时的纯化原代人 T 细胞中基础水平及 α-CD3 诱导的 p38 磷酸化[3]。
AG-012986 (dihydrochloride) (250 nM；16 小时) 可迅速诱导 PBMC 凋亡，且与细胞分裂无关[4]。

AG-012986 (dihydrochloride) (50-200 nM；8 小时) 诱导 p17 和 p19 以及 PARP 裂解体的表达[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

AG-012986 dihydrochloride 相关抗体:

Western Blot Analysis[1]

Cell Line: HCT116 human colon cancer cells
Concentration: 60 nM; 120 nM; 240 nM
Incubation Time: 8 h; 24 h
Result: Showed minimal effect on Rb Ser795 phosphorylation after treatment with up to 240 nM for 8 hours.
Induced dose-dependent hypophosphorylation of Rb Ser795 after treatment with 60 to 240 nM for 24 hours, with maximal effects at >120 nM.

Cell Cycle Analysis[1]

Cell Line: HCT116 human colon cancer cells
Concentration: 30 nM; 60 nM; 120 nM; 240 nM; 480 nM; 720 nM; 1 μM
Incubation Time: 24 h; <8 h
Result: Caused accumulation of cells in the G1 phase after treatment with 30 to 120 nM for 24 hours.
Caused accumulation of cells in the G2-M phase after treatment with ≥240 nM for 24 hours.
Failed to induce any cell cycle arrest after transient exposure (<8 hours) to up to 1 μM.

Apoptosis Analysis[1]

Cell Line: HCT116 human colon cancer cells
Concentration: 120 nM; 240 nM
Incubation Time: 8 h; 24 h
Result: Induced no apoptosis after 8 hours of treatment at any concentration.
Induced a greater proportion of apoptotic cells after treatment with ≥120 nM for 24 hours, with an IC50 of ≈160 nM.

Cell Cytotoxicity Assay[1]

Cell Line: SW620 human colon carcinoma cells
Concentration: 10 nM; 100 nM; 1000 nM
Incubation Time: 8 h; 24 h; 72 h; 320 h
Result: Showed minimal cytotoxic activity after 8 hours of treatment.
Showed moderate activity with an IC50 of 300 nmol/L after 24 hours.
Showed substantial cytotoxicity with an IC50 <100 nmol/L at treatment durations ≥72 hours, with near-complete cell kill at 1000 nM after 320 hours.

Cell Viability Assay[2]

Cell Line: human Müller cell line MIO-M1
Concentration: 200 nM; 500 nM
Incubation Time: 24 h
Result: Caused a dose-dependent decrease in cell viability (measured via MTS assay) and a corresponding dose-dependent increase in cell death (measured via LDH release).
Reduced cell viability by ~25% relative to controls at maximal response.
Increased LDH release by ~2-fold relative to controls at maximal response.
Produced significant effects at 200 nM.
Achieved maximal response at 500 nM.

Western Blot Analysis[3]

Cell Line: primary human PBMCs
Concentration: 50 nM; 200 nM
Incubation Time: 8 h
Result: Induced cleavage of caspase-3 and PARP.

Western Blot Analysis[3]

Cell Line: purified primary human T cells
Concentration: 50 nM; 250 nM; 50 nM plus α-CD3 antibody (1 μg/mL; 24 h); 250 nM plus α-CD3 antibody (1 μg/mL; 24 h)
Incubation Time: 20 min
Result: Showed almost a complete lack of active capase-3 after 24 h stimulation with CD3 antibody.

Western Blot Analysis[3]

Cell Line: purified primary human T cells
Concentration: 50 nM; 250 nM; 50 nM plus plate-bound α-CD3 antibody (1 μg/mL; 16 h); 250 nM plus plate-bound α-CD3 antibody (1 μg/mL; 16 h)
Incubation Time: 20 min
Result: Inhibited both basal and α-CD3-induced p38 phosphorylation in purified primary human T cells with or without stimulation.

Apoptosis Analysis[4]

Cell Line: human donor PBMCs
Concentration: 250 nM
Incubation Time: 16 h
Result: Induced apoptosis in approximately 80% of the cells.

Western Blot Analysis[4]

Cell Line: human donor PBMCs
Concentration: 50 nM; 200 nM
Incubation Time: 8 h
Result: Induced the presence of p17 and p19 and the cleaved form of PARP.
药代动力学
(Parmacokinetics)
Species Dose Route Cmax AUC0-24 AUC0-t AUC T1/2
Mice[1] 6, 12, 25, 50, 75 mg/kg i.p. 1.08 μg/mL / / 1.32 μg·h/mL 1 h
Mice[1] 10, 20, 40 mg/kg s.c. 0.182 μg/mL 3.92 μg·h/mL 27.5 μg·h/mL / /
体内研究
(In Vivo)

AG-012986 (dihydrochloride) (8.8-40 mg/kg；皮下注射；每天；持续 12 天) 在 11 种人源异种移植肿瘤模型中的 10 种均表现出强效的、剂量依赖性抗肿瘤效力，在最大耐受剂量或接近最大耐受剂量时肿瘤生长抑制率 ＞83%，且其效力与持续的最低有效血浆水平相关，而非血浆峰值浓度[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Severe combined immunodeficient; athymic NCr-nu/nu (human tumor xenograft model, implanted s.c. with 2 million COLO205 or H522 cells in 30% Matrigel)[1]
Dosage: 20 mg/kg; 40 mg/kg; 8.8 mg/kg; 17.5 mg/kg; 35 mg/kg
Administration: s.c.; once a day for 12 d
Result: Induced 94.7% TGI and a net log tumor cell kill of 1.20 in COLO205 colon carcinoma models at 40 mg/kg daily for 12 days.
Induced 71.3% TGI and a net log tumor cell kill of 0.64 in COLO205 colon carcinoma models at 20 mg/kg daily for 12 days.
Induced 22.2% TGI and a negative net log tumor cell kill of -0.21 in COLO205 colon carcinoma models at 10 mg/kg daily for 12 days.
Animal Model: Severe combined immunodeficient; athymic NCr-nu/nu (human tumor xenograft model, implanted i.p. with 2 million COLO205 cells in 30% Matrigel)[1]
Dosage: 10 mg/kg; 20 mg/kg; 40 mg/kg
Administration: i.p.; single application
Result: Reduced Rb Ser795 phosphorylation by >80% and induced PARP cleavage in COLO205 tumor tissue at 24 hours post single 20 or 40 mg/kg i.p. dose.
Reduced Rb Ser795 phosphorylation by 50% and did not induce PARP cleavage in COLO205 tumor tissue at 24 hours post single 10 mg/kg i.p. dose.
Significantly decreased BrdUrd uptake (S phase activity) in COLO205 tumors between 12 and 24 hours post single 20 mg/kg i.p. dose.
分子量

532.43

Formula

C22H25Cl2F2N5O2S
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

AG-012986 dihydrochloride 相关分类

  • 摩尔计算器

  • 稀释计算器

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量   浓度   体积   分子量 *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

浓度 (start) × 体积 (start) = 浓度 (final) × 体积 (final)
× = ×
C1   V1   C2   V2
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

AG-012986486414-32-8AG012986AG 012986CDKCyclin dependent kinaseprimary human PBMCsCDK2CDK1primary human T cellsCDK9CDK4/6HCT116 human colon cancer cellsMIO-M1 Müller cellsSW620 human colon carcinoma cellsCDK5Inhibitorinhibitorinhibit

您最近查看的产品:

Your information is safe with us. * Required Fields.

   产品名称：

  

* 需求量：

* 客户姓名：

 

* Email：

* 电话：

 

* 公司或机构名称：

   留言给我们：

Bulk Inquiry

Inquiry Information

产品名称：
AG-012986 dihydrochloride
目录号：
HY-182470
需求量：

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

   产品名称：

  

* Lot #：

* 客户姓名：

 

* Email：

   电话：

 

* 部门：

* 公司或机构名称：

 

   留言给我们：

Request for HNMR Report

We have received your request and will respond to you as soon as possible.

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z