YW3-56
目录号 : GC33261
YW3-56是有效的肽酰精氨酸脱亚胺酶(PAD)抑制剂，其对PAD4的IC50值为1-5μM。
Cas No.:1374311-17-7
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
YW3-56 is a potent peptidylarginine deiminase (PAD) inhibitor, with an IC50 of 1-5 μM for PAD4.
Compared with Cl-amidine, YW3-56 shows >60-fold increase in cell growth inhibition efficacy (IC50 about 2.5 μM) but only 5-fold increase in PAD4 inhibition (IC sub>50 about 1-5 μM). At 2-4 μM concentrations, YW3-56 displays mainly cytostatic effects by slowing cell division, whereas at higher concentrations, it exerts cytotoxic effects by altering cell morphology and killing cells[1].
[1]. Wang Y, et al. Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and t he mammalian target of rapamycin complex 1 activity. J Biol Chem. 2012 Jul 27;287(31):25941-53.
| Cas No. | 1374311-17-7 | SDF | |
| Canonical SMILES | O=C(C1=CC=C2C=C(N(C)C)C=CC2=C1)N[C@H](C(NCC3=CC=CC=C3)=O)CCCNC(CCl)=N | ||
| 分子式 | C27H32ClN5O2 | 分子量 | 494.03 |
| 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 | 2.0242 mL | 10.1208 mL | 20.2417 mL |
| 5 mM | 0.4048 mL | 2.0242 mL | 4.0483 mL |
| 10 mM | 0.2024 mL | 1.0121 mL | 2.0242 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。
Neutrophil peptidyl arginine deiminase-4 has a pivotal role in ischemia/reperfusion-induced acute kidney injury
Kidney Int 2018 Feb;93(2):365-374.PMID:29061334DOI:10.1016/j.kint.2017.08.014.
Ischemia/reperfusion is a common cause of acute kidney injury (AKI). However, mechanisms underlying the sudden loss in kidney function and tissue injury remain to be fully elucidated. Here, we investigated the role of peptidyl arginine deiminase-4 (PAD4), which converts arginine to citrulline and plays a role in epigenetic regulation and inflammation, in renal ischemia/reperfusion injury. PAD4 expression was highly induced in infiltrating leukocytes 24 hours following renal ischemia and reperfusion. This induction was accompanied by citrullination of histone H3 and formation of neutrophil extracellular traps in kidneys of wild-type mice. By contrast, PAD4-deficient mice did not form neutrophil extracellular traps, expressed lower levels of pro-inflammatory cytokines and were partially protected from renal ischemia/reperfusion-induced AKI. Furthermore, PAD4-deficient mice recovered kidney function 48 hours after ischemia/reperfusion, whereas kidney function in the wild-type mice progressively worsened. Administration of DNase I, which degrades neutrophil extracellular traps or the PAD-specific inhibitor YW3-56 before ischemia, partially prevented renal ischemia/reperfusion-induced AKI. Notably, transfer of neutrophils from wild-type, but not from PAD4-deficient mice, was sufficient to restore renal neutrophil extracellular trap formation and impair kidney function following renal ischemia/reperfusion. Thus, neutrophil PAD4 plays a pivotal role in renal ischemia/reperfusion-induced AKI.
ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer Cells
Mol Cancer Ther 2015 Apr;14(4):877-88.PMID:25612620DOI:10.1158/1535-7163.MCT-14-1093-T.
We previously reported that a pan-PAD inhibitor, YW3-56, activates p53 target genes to inhibit cancer growth. However, the p53-independent anticancer activity and molecular mechanisms of YW3-56 remain largely elusive. Here, gene expression analyses found that ATF4 target genes involved in endoplasmic reticulum (ER) stress response were activated by YW3-56. Depletion of ATF4 greatly attenuated YW3-56-mediated activation of the mTORC1 regulatory genes SESN2 and DDIT4. Using the ChIP-exo method, high-resolution genomic binding sites of ATF4 and CEBPB responsive to YW3-56 treatment were generated. In human breast cancer cells, YW3-56-mediated cell death features mitochondria depletion and autophagy perturbation. Moreover, YW3-56 treatment effectively inhibits the growth of triple-negative breast cancer xenograft tumors in nude mice. Taken together, we unveiled the anticancer mechanisms and therapeutic potentials of the pan-PAD inhibitor YW3-56.
Folded Conformation, Cyclic Pentamer, Nano-Structure and PAD4 Binding Mode of YW3-56
J Phys Chem C Nanomater Interfaces 2013 May 16;117(19):10070-10078.PMID:23795230DOI:10.1021/jp311726k.
The physical and chemical mechanisms of small molecules with pharmacological activity forming nano-structures are developing into a new field of nano-medicine. By using ROESY 2D NMR spectroscopy, trandem mass spectroscopy, transmission electron microscopy and computer-assisted molecular modeling, this paper demonstrated the contribution of the folded conformation, the intra- and intermolecular π-π stacking, the intra- and intermolecular hydrogen bonds, and the receptor binding free energy of 6-dimethylaminonaph-2-yl-{N-S-[1-benzylcarba-moyl-4-(2-chloroacetamidobutyl)]-carboxamide (YW3-56) to the rapid formation of nano-rings and the slow formation of nano-capsules. Thus we have developed a strategy that makes it possible to elucidate the physical and chemical mechanisms of bioactive small molecules forming nano-structures.
PAD4 inhibitor promotes DNA damage and radiosensitivity of nasopharyngeal carcinoma cells
Environ Toxicol 2021 Nov;36(11):2291-2301.PMID:34363436DOI:10.1002/tox.23342.
Peptidylarginine deiminases 4 (PAD4), a kind of enzyme capable of converting protein arginine or mono-methylarginine into citrulline, has been identified to display a key role in diverse diseases. Radiotherapy is frequently used in nasopharyngeal carcinoma (NPC) treatment and induces DNA double strand breaks. In this study, whether PAD4 inhibitor YW3-56 affects the radiosensitivity of NPC cells was explored. RT-qPCR, immunofluorescence, western blot, clonogenic survival, and flow cytometry assays were used to assess the function of PAD4 and YW3-56 in NPC. We found the upregulation of PAD4 expression in NPC cells. PAD4 overexpression suppressed NPC cell apoptosis and promoted cell cycle, while PAD4 depletion had an opposite result. Moreover, the survival of NPC cells after irradiation was increased by overexpression of PAD4. PAD4 overexpression inhibited DNA damage and sensitivity of NPC cells to irradiation. Functional assays showed that YW3-56 treatment promoted DNA damage, apoptosis, and radiosensitivity of NPC cells. Importantly, YW3-56 treatment inhibited tumor growth in vivo. Overall, this study revealed the efficacy of PAD4 inhibitor YW3-56 in promoting sensitivity of NPC cells to irradiation.
Inhibition of Netosis with PAD Inhibitor Attenuates Endotoxin Shock Induced Systemic Inflammation
Int J Mol Sci 2022 Oct 31;23(21):13264.PMID:36362052DOI:10.3390/ijms232113264.
Neutrophils play a pivotal role in innate immunity by releasing neutrophils extracellular traps (NETs). Excessive NETs are detrimental to the local tissue and further exacerbate inflammation. Protein arginine deiminases (PAD) mediate histone citrullination and NET formation that, in turn, exacerbate endotoxin shock damages. In this study, we further investigated the molecular mechanism underlying PAD and NETs in endotoxic stress in mice. The control group mice were injected with solvent, the LPS endotoxic shock group mice were intraperitoneally injected with LPS at 35 mg/kg only, while the LPS and PAD inhibitor YW3-56 treatment group mice were injected with YW3-56 at 10 mg/kg prior to the LPS injection. YW3-56 significantly prolonged the survival time of the LPS-treated mice. NETs, cfDNA, and inflammatory factors were detected by ELISA in serum, paitoneal cavity, and lung at 24 h after LPS administration. Lung injuries were detected by immunostaining, and lung tissue transcriptomes were analyzed by RNA-seq at 24 h after LPS administration. We found that YW3-56 altered neutrophil tissue homeostasis, inhibited NET formation, and significantly decreased cytokines (IL-6, TNFα and IL-1β) levels, cytokines gene expression, and lung tissue injury. In summary, NET formation inhibition offers a new avenue to manage inflammatory damages under endotoxic stress.