AS2521780
目录号 : GC31959
AS2521780是新颖的PKCθ选择性抑制剂，IC50值为0.48nM。
Cas No.:1214726-89-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Human peripheral T cells are incubated with AS2521780 and anti-human CD28 (0.5 μg/mL). After 48 h incubation, cell proliferation is detected using a CellTiter-Glo Luminescent Cell Viability Assay[1]. |
Animal experiment: | AS2521780 or vehicle is orally administered twice daily from Day 1 to 24. On Day 25, the left hind paw of each rat is dissected above the ankle joint and fixed in 10% neutral buffered formalin. After decalcification, the paws are embedded in paraffin, sectioned longitudinally and stained with hematoxylin and eosin[1]. |
References: [1]. Fukahori H, et al. Effect of AS2521780, a novel PKCθ selective inhibitor, on T cell-mediated immunity. Eur J Pharmacol. 2014 Dec 15;745:217-22. | |
AS2521780 is a novel PKCθ selective inhibitor with an IC50 of 0.48 nM.
AS2521780 exerts potent inhibition of recombinant human PKCθ enzyme activity (IC50=0.48 nM), which is more than 30-fold higher than that of other PKC isoforms. Further, AS2521780 exerts little or no inhibition on other protein kinases. AS2521780 suppresses CD3/CD28-induced Interleukin-2 (IL-2) gene transcription in Jurkat T cells and proliferation of human primary T cells. AS2521780 also suppresses concanavalin A-induced cytokine production by rat splenocytes and monkey peripheral blood mononuclear cells with similar potency[1].
AS2521780 significantly reduces paw swelling in a dose-dependent manner in a rat model of adjuvant-induced arthritis[1].
[1]. Fukahori H, et al. Effect of AS2521780, a novel PKCθ selective inhibitor, on T cell-mediated immunity. Eur J Pharmacol. 2014 Dec 15;745:217-22.
| Cas No. | 1214726-89-2 | SDF | |
| Canonical SMILES | CSC1=C(CNC2=NC=C(C#N)C(NC[C@@]3(C[C@@H](C4)C5NC[C@H]6CC[C@H](O)CC6)C[C@H]4C[C@H]5C3)=N2)C=CC=N1 | ||
| 分子式 | C30H41N7OS | 分子量 | 547.76 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8256 mL | 9.1281 mL | 18.2562 mL |
| 5 mM | 0.3651 mL | 1.8256 mL | 3.6512 mL |
| 10 mM | 0.1826 mL | 0.9128 mL | 1.8256 mL |
| 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 | ul | |
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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Effect of AS2521780, a novel PKCθ selective inhibitor, on T cell-mediated immunity
T cell-mediated immunity is central to the pathogenesis of autoimmune diseases, and is a target in the development of alternative therapeutic strategies with reduced adverse effects on other cell types and organs. Protein kinase C (PKC) is a family of serine/threonine kinases, with knockout of the PKCθ isoform in mice resulting in defective T cell activation. However, the effects of selective inhibition of PKCθ by small-molecule compounds on T cell signaling are still unknown. Here, we evaluated the effect of the novel PKCθ inhibitor AS2521780 on T cell activation and joint inflammation in a rat model of arthritis. AS2521780 exerted potent inhibition of recombinant human PKCθ enzyme activity (IC50=0.48 nM), which was more than 30-fold higher than that of other PKC isoforms. Further, AS2521780 exerted little or no inhibition on other protein kinases. AS2521780 suppressed CD3/CD28-induced Interleukin-2 (IL-2) gene transcription in Jurkat T cells and proliferation of human primary T cells. AS2521780 also suppressed concanavalin A-induced cytokine production by rat splenocytes and monkey peripheral blood mononuclear cells with similar potency. Moreover, AS2521780 significantly reduced paw swelling in a dose-dependent manner in a rat model of adjuvant-induced arthritis. These results indicate that PKCθ is an attractive drug target and AS2521780 is a potential immunosuppressant for T cell-mediated autoimmune diseases.
Effect of novel PKCθ selective inhibitor AS2521780 on acute rejection in rat and non-human primate models of transplantation
Selective inhibition of protein kinase Cθ (PKCθ) may be useful in inducing T cell-specific immunosuppression with a reduced rate of side effects. To our knowledge, however, no reports have been published regarding the selective inhibition of PKCθ by small-molecule compounds in animal models of allograft rejection. Here, we investigated the effect of the newly synthesized PKCθ selective inhibitor AS2521780 in mono- and combination therapies on acute rejection in ACI-to-Lewis rat cardiac and non-human primate (NHP) renal transplantation models. In the rat cardiac transplantation model, AS2521780 significantly prolonged graft survival to 14days at 10mg/kg twice daily (b.i.d.) and to 20days at 30mg/kg b.i.d. In contrast, acute rejection occurred in all recipients in the non-treated group by Days 5 or 6 post-transplantation. Significant improvements (P<0.001) in graft survival were observed following treatment with a combination of AS2521780 at 3mg/kg b.i.d. and a suboptimal dose of tacrolimus (0.02mg/kg) or mycophenolate mofetil (15mg/kg). In the NHP renal transplantation model, AS2521780 at 3mg/kg b.i.d. and tacrolimus at 1mg/kg (suboptimal dose) significantly improved graft survival compared to tacrolimus alone (P<0.05). The present study of AS2521780 in rat cardiac and NHP renal transplantation models demonstrates the potential of PKCθ as a novel drug target for organ transplantation. As AS2521780 was well tolerated and the dose of tacrolimus or mycophenolate mofetil can be reduced when used in combination with this drug, immunosuppressive regimens containing selective inhibitors of PKCθ might have good safety profiles.