Bioymifi
(Synonyms: DR5 Activator) 目录号 : GC35523
A DR5 agonist
Cas No.:1420071-30-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors. TNF-related apoptosis-inducing ligand (TRAIL or Apo2L), a member of this family, activates apoptosis in a variety of tumor cell lines by signaling through the death receptors, DR4 and DR5. Bioymifi directly activates DR5 (Kd = 1.2 ?M; IC50 = 2 ?M), inducing DR5 clustering, which leads to the initiation of FADD/caspase-8-dependent apoptosis in various cancer cells.1
1.Wang, G., Wang, X., Yu, H., et al.Small-molecule activation of the TRAIL receptor DR5 in human cancer cellsNat. Chem. Biol.984-90(2012)
| Cas No. | 1420071-30-2 | SDF | |
| 别名 | DR5 Activator | ||
| Canonical SMILES | O=C(/C(SC1=N)=C/C2=CC=C(O2)C3=CC(C(N4)=O)=C(C=C3)C4=O)N1C5=CC=C(C=C5)Br | ||
| 分子式 | C22H12BrN3O4S | 分子量 | 494.32 |
| 溶解度 | DMSO: 12.5 mg/mL (25.29 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.023 mL | 10.1149 mL | 20.2298 mL |
| 5 mM | 0.4046 mL | 2.023 mL | 4.046 mL |
| 10 mM | 0.2023 mL | 1.0115 mL | 2.023 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。
Bioymifi, a novel mimetic of TNF-related apoptosis-induced ligand (TRAIL), stimulates eryptosis
Med Oncol 2021 Oct 11;38(12):138.PMID:34633592DOI:10.1007/s12032-021-01589-5.
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a cytokine that initiates apoptosis upon binding to death receptor 5 (DR5) on cancer cells. Small molecule TRAIL mimetics have therefore been investigated as promising chemotherapeutic agents. Since anemia of chemotherapy is common, our goal is to investigate the hemolytic and eryptotic properties of novel DR5 agonist Bioymifi (BMF) and identify the underlying molecular mechanisms. Whole blood (WB) was stimulated with 100 μM of BMF, whereas red blood cells (RBCs) were treated with 10-100 μM of BMF for 24 h at 37 °C. WB was analyzed for RBC, leukocyte, and platelet indices, while RBCs were examined for hemolysis by light absorbance of free hemoglobin, membrane scrambling by Annexin V-FITC, calcium by Fluo4/AM, cellular morphology by light scatter, and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) using flow cytometry. Caspase inhibitor Z-VAD-FMK, p38 inhibitor SB203580, casein kinase 1α inhibitor D4476, receptor-interacting protein 1 inhibitor necrostatin-2, reduced glutathione, or cyclooxygenase (COX) inhibitor aspirin were added accordingly. BMF exerted dose-responsive, calcium-independent hemolysis, reduced RBC hemoglobin, significantly increased Annexin V-, Fluo4-, and DCF-positive cells, along with a dual effect on forward and side light scatter. Notably, the cytotoxic potential of BMF was significantly mitigated upon pharmacological inhibition of p38. Furthermore, BMF exhibited selective toxicity to eosinophils and significantly diminished reticulocyte hemoglobin content. Altogether, these novel findings highlight the adverse outcomes of BMF exposure on RBC physiology and provide the first toxicological assessment of BMF as an antitumor agent.
Death receptor-dependent apoptosis and cell cycle delay induced by Bioymifi in human cervical cancer cells
Pak J Pharm Sci 2022 Jul;35(4):1031-1036.PMID:36008899doi
In chemotherapy applied against cervical cancer, non-specific cytotoxicity and drug resistance that develops over time are trying to be overcome. Therefore, the development of effective and innovative chemotherapeutic drugs for the treatment is among the priority issues in the medical field. The anticancer activity of the Bioymifi, which can activate apoptosis by inducing DR-5 clustering and aggregation against the human cervical cancer cell line, was investigated in the current study. The cytotoxic activity of Bioymifi on the HeLa cell line was identified using XTT assay. The pathway of the cell death mechanism was analyzed through the cell cycle and Annexin V assays by the flow cytometry. DAPI staining assay was applied under fluorescence microscopy to examine the nuclear morphology. Bioymifi appeared to have a remarkable IC50 value (11.75μM) against HeLa cells. The cell cycle analysis demonstrated the increase of Bioymifi cured HeLa cells in the S phase. And also, 11.75µM of Bioymifi caused a significantly higher apoptotic effect compared to control. In addition, in vitro immunofluorescence experiments of this study represented that Bioymifi reduced Ki-67 localization in HeLa cells. Bioymifi has significantly anticancer actions in Human cervix cancer in vitro and can be combined with standard treatment.
Dissecting Programmed Cell Death with Small Molecules
Acc Chem Res 2020 May 19;53(5):1034-1045.PMID:32297735DOI:10.1021/acs.accounts.9b00600.
Programmed cell death (PCD) is fundamentally an indispensable process in all cellular activities, including cell development, wound healing, and immune surveillance of tumors (Galluzzi, L. et al. Cell Death Differ. 2018, 25, 486-541). Malfunctioning of PCD has been shown to be closely related to human diseases such as acute pancreatitis, neurodegenerative diseases, and diverse types of cancers. To date, multiple PCD processes have been discovered and the corresponding regulatory pathways have been elucidated. For example, apoptosis and autophagy are two PCD mechanisms that have been well studied by sophisticated models and probe toolkits. However, limited genetic and chemical tools for other types of PCD hamper the elucidation of their molecular mechanisms. Our group has been studying PCD using both function-oriented synthesis and chemical biology strategies, including the development of diverse chemical probes based on novel PCD modulators. For instance, in the development of downstream programmed necrosis (or necroptosis) inhibitor necrosulfonamide, we used a chemical probe to unveil a functional protein that was not previously implicated in necroptosis, mixed lineage kinase domain-like protein (MLKL). In addition, high throughput screening and medicinal chemistry enabled the discovery of Bioymifi, a small molecule agonist which selectively causes oligomerization of the death receptor 5 (DR5), to induce extrinsic apoptosis. Furthermore, we developed a biomimetic synthetic strategy based on diverse Diels-Alder reactions in the total syntheses of ainsliadimers A and B, ainsliatrimers A and B, and gonchnatiolides A-C, which are natural product inhibitors or activators for PCD. Using synthetic ainsliadimer A probe, we elucidated that ainsliadimer A inhibits the NF-κB pathway by covalently binding to Cys46 of IKKβ and triggers apoptosis of cancer cells. We have also revealed that IKKβ is allosterically inhibited by ainsliadimer A. In addition to total synthesis, we have developed a bioorthogonal click hetero-Diels-Alder cycloaddition of vinyl thioether and o-quinolinone quinone methide (TQ-ligation) to facilitate small molecule target identification. The combination of total synthesis and TQ-ligation enables subcellular imaging and identification of the cellular target of ainsliatrimer A to be PPARγ. In addition, TQ-ligation has been applied in the discovery of heat shock protein 90 (HSP90) as one of the functional target proteins for kongensin A. We also confirmed that kongensin A covalently attaches to Cys420 within HSP90 and demonstrated that kongensin A blocks the interaction between HSP90 and CDC37 and subsequently inhibits necroptosis. Our development of these diverse PCD modulators provides not only effective chemical tools for fundamental biomedical research, but also the foundation for drug discovery targeting important human diseases such as cancers and inflammation caused by malfunction of PCD.
A Dual Role for Death Receptor 5 in Regulating Cardiac Fibroblast Function
Front Cardiovasc Med 2021 Aug 30;8:699102.PMID:34527710DOI:10.3389/fcvm.2021.699102.
The fibrotic response is involved in nearly all forms of heart failure and dysregulated responses can lead to enhanced cardiac dysfunction. TNF-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor (DR) 5, are associated with multiple forms of heart failure, but their role in the heart is poorly defined. Our previous study identified DR5 expression on cardiac fibroblasts however, the impact of DR5 on fibroblast function remains unexplored. To investigate the role of DR5 in cardiac fibroblasts, a variety of fibroblast functions were examined following treatment with the endogenous ligand, TRAIL, or small molecule agonist, Bioymifi. DR5 activation did not induce apoptosis in naïve fibroblasts but activated ERK1/2 signaling to increase proliferation. However, upon activation and differentiation to myofibroblasts, DR5 expression was elevated, and DR5 agonists induced caspase 3 activation resulting in myofibroblast apoptosis. To investigate the impact of DR5 regulation of fibroblasts in vivo, a chronic isoproterenol administration model of heart failure was used. Wild-type (WT) mice receiving isoproterenol had increased hypertrophy, cardiomyocyte death, and fibrosis and decreased contractility compared to vehicle treated animals. DR5 knockout (KO) mice had no overt baseline phenotype however, following isoproterenol infusion, increased cardiomyocyte death and hypertrophy in comparison to isoproterenol treated WT animals was observed. DR5KO mice had an augmented fibrotic response with isoproterenol treatment compared with WT, which corresponded with additional decreases in contractility. These findings identify a dual role for DR5 in cardiac fibroblast function through enhanced naïve fibroblast proliferation, which switches to a pro-apoptotic function upon differentiation to myofibroblasts. This is important in heart failure where DR5 activation suppresses maladaptive remodeling and may represent a novel therapeutic target for the treatment of heart failure.
Small-molecule activation of the TRAIL receptor DR5 in human cancer cells
Nat Chem Biol 2013 Feb;9(2):84-9.PMID:23292651DOI:10.1038/nchembio.1153.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) activates apoptosis through the death receptors DR4 and DR5. Because of its superior safety profile and high tumor specificity compared to other TNF family members, recombinant soluble TRAIL and agonistic antibodies against its receptors are actively being developed for clinical cancer therapy. Here, we describe the identification and characterization of the small molecules that directly target DR5 to initiate apoptosis in human cancer cells. The activity was initially discovered through a high-throughput chemical screen for compounds that promote cell death in synergy with a small-molecule mimetic of Smac, the antagonist for inhibitor of apoptosis protein. Structure-activity relationship studies yielded a more potent analog called Bioymifi, which can act as a single agent to induce DR5 clustering and aggregation, leading to apoptosis. Thus, this study identified potential lead compounds for the development of small-molecule TRAIL mimics targeting DR5 for cancer therapy.