| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 10 mM * 1 mL in DMSO |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| 靶点 |
RSK4 (IC50 = 15 nM); RSK3 (IC50 = 18 nM); RSK2 (IC50 = 24 nM); RSK4 (IC50 = 15 nM); RSK1 (IC50 = 31 nM)
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|---|---|
| 体外研究 (In Vitro) |
BI-D1870 抑制 RSK1、RSK2、RSK3 和 RSK4，IC50 为 10-30 nM，但在 100 倍高浓度下测试时不会显着抑制其他 10 种 AGC 激酶成员和 40 多种其他蛋白激酶。在人胚肾 293 细胞和 Rat-2 细胞中，BI-D1870 具有细胞渗透性，并抑制 RSK 介导的佛波酯和 EGF 诱导的糖原合酶激酶激酶 3β 和 LKB1 的磷酸化。其他六种 AGC 激酶的激动剂触发的底物磷酸化不受 BI-D1870 的影响。此外，BI-D1870 不会阻断佛波酯或 EGF 引起的 CREB 磷酸化。[1]
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| 体内研究 (In Vivo) |
注射 BI-D1870 (0.5 mg/kg) 的实验性自身免疫性脑脊髓炎 (EAE) 小鼠表现出迟发性神经缺陷，但没有明显的体重减轻。组织病理学分析显示对照小鼠的脊髓中有炎症细胞浸润和脱髓鞘，但 BI-D1870 治疗的小鼠则没有。 BI-D1870 可防止 TH1 或 TH17 细胞浸润至中枢神经系统。
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| 酶活实验 |
将纯化的 His6–RSK1、His6–RSK2 或 GST–RSK2 1–389:S381E (1–2 单位/mL) 在含有 30 μM 底物肽 (KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK) 的缓冲液 A 中的 50 μL 测定混合物中于 30 °C 测定 10 分钟)、10 mM 醋酸镁和 100 μM [γ-32P]ATP。如前所述，停止并检查反应。 1个酶单位是1分钟内催化1nmol底物肽磷酸化所需的量。为了测定 HEK-293 或 Rat-2 细胞裂解物中的 RSK 和 MSK1，从细胞裂解物中对这些激酶进行免疫沉淀（RSK 为 0.1 mg 裂解物蛋白，MSK1 为 0.3 mg），并且对于 RSK 测定，免疫沉淀物用缓冲液 A 含有 1 mM ATP，并在测定前使用缓冲液 A 两次，作为预防措施，确保 BI-D1870 从 RSK 同工型解离。
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| 细胞实验 |
使用 MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴化物]测定法评估细胞生长，重复六次。在 96 孔平底板中，将细胞 (5 103/200 L) 接种 24 小时，然后在指定的时间内暴露于不同浓度的测试剂中。除去培养基后，加入200μL含有0.5mg/mL浓度的MTT的培养基，并将细胞在37℃下孵育2小时。除去培养基后，将每孔的还原 MTT 染料溶解在 200 L DMSO 中。 Synergy HT 多模式酶标仪在 570 nm 处用于测量吸光度。
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| 动物实验 |
Myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 MEVGWYRSPFSRVVHLYRNGK) (BEX) is used to induce EAE in C57/BL6J mice. Mice are given s.c. injections of 200 g of MOG peptide emulsified in 100 μL of PBS, 100 l of complete Freund's adjuvant (CFA), and five mg/mL of Mycobacterium tuberculosis. Additionally, on days 0 and 2, 500 ng of pertussis toxin is intravenously injected. Two days after receiving the MOG peptide vaccination, mice are given an intraperitoneal injection of the RSK inhibitor (BI-D1870; 0.5 mg/kg), which is repeated every other day for 11 days. As controls, mice are given only dimethyl sulfoxide (DMSO) solution. On a scale from zero (no disease) to six (death), paralysis is rated as follows: one (tail limpness), two (hind limb weakness), three (hind limb paralysis), four (fore limb weakness), five (quadriplegia), and six (no disease). Hematoxylin and eosin (H & E) staining is carried out on CNS samples after they have been cut at a thickness of 4 m and fixed with 4% paraformaldehyde for histological analysis.
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| 参考文献 |
| 分子式 |
C19H23F2N5O2
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|---|---|
| 分子量 |
391.4150
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| 精确质量 |
391.18198
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| 元素分析 |
C, 58.30; H, 5.92; F, 9.71; N, 17.89; O, 8.18
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| CAS号 |
501437-28-1
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| 相关CAS号 |
501437-28-1
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| 外观&性状 |
Pale orange to brown solid powder
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| SMILES |
CC1C(=O)N(C2=CN=C(N=C2N1CCC(C)C)NC3=CC(=C(C(=C3)F)O)F)C
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| InChi Key |
DTEKTGDVSARYDS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H23F2N5O2/c1-10(2)5-6-26-11(3)18(28)25(4)15-9-22-19(24-17(15)26)23-12-7-13(20)16(27)14(21)8-12/h7-11,27H,5-6H2,1-4H3,(H,22,23,24)
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| 化学名 |
2-((3,5-difluoro-4-hydroxyphenyl)amino)-8-isopentyl-5,7-dimethyl-7,8-dihydropteridin-6(5H)-one
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| 别名 |
BI D1870; BID1870; BI-D1870
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外) |
DMSO: ~78 mg/mL (~199.3 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
|---|---|
| 溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5548 mL | 12.7740 mL | 25.5480 mL | |
| 5 mM | 0.5110 mL | 2.5548 mL | 5.1096 mL | |
| 10 mM | 0.2555 mL | 1.2774 mL | 2.5548 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
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 ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
Structure-activity relationships for dihydropteridinone interactions with kinases and bromodomains and structural comparison of inhibitor binding modes.Nat Chem Biol.2014 Apr;10(4):305-12. |
Responses of FLT3 inhibitor-sensitive and -resistant AML cell lines to TG-101348 and BET inhibitors.Nat Chem Biol.2014 Apr;10(4):305-12. |
Functional activities of dual kinase/bromodomain inhibitors in primary human cell disease models. a, Test agents and kinase or BET benchmark inhibitors were tested for effects on protein biomarkers (x-axis) in 12 primary human cell-based BioMAP systems () at 7 doses. b, BI-2536 (BI) and TG-101348 (TG) and inhibitors targeting either kinases, including JAK (tofacitinib (Tofa) and ruxolitinib (Ruxo)) or PLK (GSK-461364A (GSK)), or BET bromodomains (JQ1, I-BET, PFI-1, and I-BET 151) were profiled in the BioMAP Diversity PLUS panel at 6 doses to generate dose-specific compound signature activity profiles. |
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