tBID
目录号 : GC37746
tBID是同源结构域相互作用蛋白激酶2 (HIPK2) 的选择性抑制剂，IC50值为0.33 μM。
Cas No.:1639895-85-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
tBID is a selective inhibitor of homeodomain-interacting protein kinase 2 (HIPK2) with an IC50 of 0.33 µM. IC50: 0.33 µM (HIPK2)[1]
Homeodomain-interacting protein kinase 2 (HIPK2) is a Ser/Thr kinase controlling cell proliferation and survival. TBID, displays toward HIPK2 unprecedented efficacy (IC50=0.33 µM) and selectivity (Gini coefficient 0.592 out of a panel of 76 kinases). The two other members of the HIPK family, HIPK1 and HIPK3, are also inhibited by TBID albeit less efficiently than HIPK2. The mode of action of TBID is competitive with respect to ATP, consistent with modelling. TBID interacts with the hinge region through hydrophobic interactions between Val 213, Val 261, Phe 277, Leu 280, Met 331, Ile 345, and the tetrabromine moiety, while the symmetric nitrogen atom at position 3 interacts with the catalytic Lys 228, thus playing a crucial role in the binding architecture[1].
[1]. Cozza G, et al. Synthesis and properties of a selective inhibitor of homeodomain-interacting protein kinase 2 (HIPK2). PLoS One. 2014 Feb 24;9(2):e89176.
| Cas No. | 1639895-85-4 | SDF | |
| Canonical SMILES | O=C1N(C2=NC=CN2)C(C3=C(Br)C(Br)=C(Br)C(Br)=C31)=O | ||
| 分子式 | C11H3Br4N3O2 | 分子量 | 528.78 |
| 溶解度 | DMSO: 26 mg/mL (49.17 mM and warming) | 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 | 1.8911 mL | 9.4557 mL | 18.9115 mL |
| 5 mM | 0.3782 mL | 1.8911 mL | 3.7823 mL |
| 10 mM | 0.1891 mL | 0.9456 mL | 1.8911 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。
BCL-2-family protein tBID can act as a BAX-like effector of apoptosis
EMBO J 2022 Dec 17;41(2):e108690.PMID:34931711DOI:10.15252/embj.2021108690.
During apoptosis, the BCL-2-family protein tBID promotes mitochondrial permeabilization by activating BAX and BAK and by blocking anti-apoptotic BCL-2 members. Here, we report that tBID can also mediate mitochondrial permeabilization by itself, resulting in release of cytochrome c and mitochondrial DNA, caspase activation and apoptosis even in absence of BAX and BAK. This previously unrecognized activity of tBID depends on helix 6, homologous to the pore-forming regions of BAX and BAK, and can be blocked by pro-survival BCL-2 proteins. Importantly, tBID-mediated mitochondrial permeabilization independent of BAX and BAK is physiologically relevant for SMAC release in the immune response against Shigella infection. Furthermore, it can be exploited to kill leukaemia cells with acquired venetoclax resistance due to lack of active BAX and BAK. Our findings define tBID as an effector of mitochondrial permeabilization in apoptosis and provide a new paradigm for BCL-2 proteins, with implications for anti-bacterial immunity and cancer therapy.
Involvement of cardiolipin in tBID-induced activation of BAX during apoptosis
Chem Phys Lipids 2014 Apr;179:70-4.PMID:24333953DOI:10.1016/j.chemphyslip.2013.12.002.
Permeabilization of the outer mitochondrial membrane constitutes an essential step in response to a wide range of apoptotic stimuli. Pro-apoptotic members of the BCL-2 family such as BAX and BAK are responsible for disrupting the integrity of the mitochondrial outer membrane, thereby allowing the release of apoptogenic factors including cytochrome c, which activate caspases in the cytosol. How BAX and BAK are activated during apoptosis is still not fully understood. Cooperation between tBID and the mitochondrial-specific phospholipid cardiolipin has been suggested to promote BAX or BAK oligomerization. Here we review the evidence for and against a role for cardiolipin in BAX and BAK activation and in the subsequent onset of apoptosis.
Bcl-xL inhibits tBID and Bax via distinct mechanisms
Faraday Discuss 2021 Dec 24;232(0):86-102.PMID:34528939DOI:10.1039/d0fd00045k.
The proteins of the Bcl-2 family are key regulators of apoptosis. They form a complex interaction network in the cytosol and in cellular membranes, whose outcome determines mitochondrial permeabilization and commitment to death. However, we still do not understand how the action of the different family members is orchestrated to regulate apoptosis. Here, we combined quantitative analysis of the interactions and the localization dynamics of the family representatives Bcl-xL, Bax and tBID, in living cells. We discovered that Bax and tBID are able to constitutively shuttle between cytosol and mitochondria in the absence of other Bcl-2 proteins. Bcl-xL clearly stabilized tBID at mitochondria, where they formed tight complexes. In contrast, Bcl-xL promoted Bax retrotranslocation to the cytosol without affecting its shuttling rate, but by forming weak inhibitory mitochondrial complexes. Furthermore, analysis of phospho-mimetics of Bcl-xL suggested that phosphorylation regulates the function of Bcl-xL via multiple mechanisms. Altogether, our findings support a model in which the Bcl-2 network not only modulates protein/protein interactions among the family members, but also their respective intracellular localization dynamics, to regulate apoptosis.
Early process development of API applied to poorly water-soluble tBID
Eur J Pharm Biopharm 2018 May;126:2-9.PMID:29339163DOI:10.1016/j.ejpb.2018.01.008.
Finding and optimising of synthesis processes for active pharmaceutical ingredients (API) is time consuming. In the finding phase, established methods for synthesis, purification and formulation are used to achieve a high purity API for biological studies. For promising API candidates, this is followed by pre-clinical and clinical studies requiring sufficient quantities of the active component. Ideally, these should be produced with a process representative for a later production process and suitable for scaling to production capacity. This work presents an overview of different approaches for process synthesis based on an existing lab protocol. This is demonstrated for the production of the model drug 4,5,6,7-tetrabromo-2-(1H-imidazol-2-yl) isoindolin-1,3-dione (tBID). Early batch synthesis and purification procedures typically suffer from low and fluctuating yields and purities due to poor process control. In a first step the literature synthesis and purification procedure was modified and optimized using solubility measurements, targeting easier and safer processing for consecutive studies.
Mitochondrial targeting of tBID/Bax: a role for the TOM complex?
Cell Death Differ 2009 Aug;16(8):1075-82.PMID:19521421DOI:10.1038/cdd.2009.61.
The release of pro-apoptotic proteins from the mitochondria is a key event in cell death signaling that is regulated by Bcl-2 family proteins. For example, cleavage of the BH3-only protein, Bid, by multiple proteases leads to the formation of truncated Bid that, in turn, promotes the insertion/oligomerization of Bax into the mitochondrial outer membrane, resulting in pore formation and the release of proteins residing in the intermembrane space. Bax, a monomeric protein in the cytosol is targeted to the mitochondria by a yet unknown mechanism. Several proteins of the outer mitochondrial membrane have been proposed to act as receptors for Bax, among them the voltage-dependent anion channel, VDAC, and the mitochondrial protein translocase of the outer membrane, the TOM complex. Alternatively, the unique mitochondrial phospholipid, cardiolipin, has been ascribed a similar function. Here, we review recent work on the mechanisms of activation and the targeting of Bax to the mitochondria and discuss the advantages and limitations of the methods used to study this process.