BB-Cl-Amidine
目录号 : GC31755
BB-Cl-Amidine 是一种肽基精氨酸脱氨酶 (PAD) 抑制剂，常用于研究 PAD 功能。
Cas No.:1802637-39-3
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');)
;)
BB-Cl-Amidine, a peptidylarginine deminase (PAD) inhibitor, is frequently used to study PAD function.[1]
In vitro experiment it shown that after 48 h of treatment with 0 to 20 μM BB-Cl-Amidine caused a dose-dependent decrease in cell viability in canine and feline mammary tumor cells.[1] In vitro, Cl-amidine and BB-Cl-Amidine show similar potencies and selectivities in U2OS cells, the cellular potency of BB-Cl-Amidine is increased by more than 20-fold, with EC50 values of 8.8±0.6 μM in U2OS osteosarcoma cells.[5]
In vivo efficacy test it exhibited that treatment with 1 μg/ml BB-Cl-Amidine intraperitoneally for two weeks in xenograft mice, BB-Cl-Amidine-treated tumors became crusty and the surrounding skin showed hair loss. There was an or a slight increase in apoptotic cells in the BB-Cl-Amidine-treated canine or feline xenograft tumors.[1] In vitro, at concentrations around 15-20 μM and 4 μM, respectively, BB-Cl-Amidine inhibited both PAD isoforms in a dose-dependent manner with 90% inhibition of PAD2 and PAD4.[2]
In vivo, arthritic mice were treated with 10 mg/kg BB-Cl-Amidine, there was a reduction in inflammation and joint destruction.[3] In vivo, treatment with 1 mg/kg BB-Cl-Amidine intraperitoneally and Ac-YVAD-cmk (a pyroptosis inhibitor) attenuated NET levels in BALF and neutrophil infiltration in alveoli. [4] In vivo, treatment with 1 mg/kg BB-Cl-Amidine subcutaneously obviously reduced splenomegaly in MRL/lpr mice and improved endothelium-dependent vasorelaxation.[5]
References:
[1] Ledet MM, et al. BB-Cl-Amidine as a novel therapeutic for canine and feline mammary cancer via activation of the endoplasmic reticulum stress pathway. BMC Cancer. 2018 Apr 12;18(1):412.
[2] Martín Monreal MT, et al. Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4. Front Immunol. 2021 Oct 19;12:716250.
[3] Kawalkowska J, et al. Abrogation of collagen-induced arthritis by a peptidyl arginine deiminase inhibitor is associated with modulation of T cell-mediated immune responses. Sci Rep. 2016 May 23;6:26430.
[4] Li H, Li Y, et al. Neutrophil Extracellular Traps Augmented Alveolar Macrophage Pyroptosis via AIM2 Inflammasome Activation in LPS-Induced ALI/ARDS. J Inflamm Res. 2021 Sep 21;14:4839-4858.
[5] Knight JS, et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann Rheum Dis. 2015 Dec;74(12):2199-206.
BB-Cl-Amidine 是一种肽基精氨酸脱氨酶 (PAD) 抑制剂，常用于研究 PAD 功能。[1]
体外实验表明，在用 0 至 20 μM BB-Cl-Amidine 处理 48 小时后，犬和猫乳腺肿瘤细胞的细胞活力呈剂量依赖性降低。[1] 在体外，Cl-amidine 和 BB-Cl-Amidine 在 U2OS 细胞中表现出相似的效力和选择性，BB-Cl-Amidine 的细胞效力增加超过 20 倍，在 U2OS 中的 EC50 值为 8.8±0.6 μM骨肉瘤细胞.[5]
体内药效试验表明，在异种移植小鼠中用 1 μg/ml BB-Cl-Amidine 腹腔注射两周，BB-Cl-Amidine 处理的肿瘤变得结痂，周围皮肤出现脱发。在 BB-Cl-Amidine 处理的犬科动物或猫科动物异种移植肿瘤中，凋亡细胞有所增加或略有增加。[1] 在体外，浓度分别约为 15-20 μM 和 4 μM , BB-Cl-Amidine 以剂量依赖性方式抑制两种 PAD 亚型，对 PAD2 和 PAD4 的抑制率为 90%。[2]
在体内，用 10 mg/kg BB-Cl-Amidine 治疗关节炎小鼠，炎症和关节破坏减少。[3] 在体内，用 1 mg/kg 治疗腹膜内注射 BB-Cl-脒和 Ac-YVAD-cmk（一种细胞焦亡抑制剂）可减弱 BALF 中的 NET 水平和肺泡中的中性粒细胞浸润。 [4] 在体内，皮下注射 1 mg/kg BB-Cl-Amidine 可显着减少 MRL/lpr 小鼠的脾肿大并改善内皮依赖性血管舒张。[5]
| Cell experiment [1]: | |
|
Cell lines |
MCF10DCIS cells |
|
Preparation Method |
MCF10DCIS cells were grown in soft agar at different concentrations of BB-CL-AMIDINE (0 µM (DMSO), or 1 µM BB-CL-AMIDINE). After 2.5 weeks, individual colonies larger than 70 µm were counted. |
|
Reaction Conditions |
0 µM or 1 µM; 2.5 weeks |
|
Applications |
There was an average of 3,536 colonies in the DMSO control whereas only 1,967 colonies were seen in the BB-CL-AMIDINE treated group after 2.5 weeks of soft agar culture. This represents a 44% decrease in the average colony formation in the presence of 1 µM BB-CL-AMIDINE, indicating a significant tumorigenic inhibition of breast cancer cells (MCF10DCIS cells) by the PADI inhibitor. |
| Animal experiment [2]: | |
|
Animal models |
Eight-week-old female NOD mice |
|
Dosage form |
1 μg/g; s.c. |
|
Preparation method |
Eight-week-old female NOD mice were used. Treatments involved subcutaneous injections with BB-Cl-amidine (1 μg/g body weight) or vehicle (25% DMSO in PBS) six times per week until 25 weeks of age for diabetes incidence or until 13 weeks of age for mechanistic studies |
|
Applications |
BB-Cl-amidine treatment fully prevented diabetes development, with all mice free of diabetes until 25 weeks of age, against 44% diabetes free in DMSO-treated mice. |
|
References: [1] Horibata S, et al. Utilization of the Soft Agar Colony Formation Assay to Identify Inhibitors of Tumorigenicity in Breast Cancer Cells. J Vis Exp. 2015 May 20;(99):e52727. [2] Sodré FMC, et al. Peptidylarginine Deiminase Inhibition Prevents Diabetes Development in NOD Mice. Diabetes. 2021 Feb;70(2):516-528. |
|
| Cas No. | 1802637-39-3 | SDF | |
| Canonical SMILES | O=C(C1=CC=C(C2=CC=CC=C2)C=C1)N[C@H](C3=NC4=CC=CC=C4N3)CCCNC(CCl)=N | ||
| 分子式 | C26H26ClN5O | 分子量 | 459.97 |
| 溶解度 | DMSO : 125 mg/mL (271.76 mM) | 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 | 2.1741 mL | 10.8703 mL | 21.7405 mL |
| 5 mM | 0.4348 mL | 2.1741 mL | 4.3481 mL |
| 10 mM | 0.2174 mL | 1.087 mL | 2.1741 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet