BDA-366

Bcl2-BH4 (Ki = 3.3 nM)

BDA-366 会触发 BCL2 的构象变化，从而导致原代细胞系和 MM（多发性骨髓瘤）细胞系发生强烈凋亡。 BDA-366 在体外和体内均可抑制肺癌细胞的生长，BDA-366 会导致 BCL2 分子构象发生变化，使其转变为死亡蛋白[1]。作为其 Bcl2 结合排他性的证据，BDA-366 不与其他 Bcl2 家族成员结合，例如 Bcl-XL、Mcl-1 或 Bfl-1/A1。 BDA-366 通过以 Bax 依赖性方式抑制 Bcl2/IP3R 与凋亡细胞之间的相互作用来诱导钙 (Ca2+) 释放 [2]。

BDA-366 的递送显着减少了 NOD-scid/IL2Rγ 缺失小鼠中人类 MM 异种移植物的生长，同时对体重或正常造血细胞具有最小的细胞毒性作用[1]。此外，在动物模型中，BDA-366 通过诱导细胞凋亡来抑制肺癌的生长。 BH4 拮抗剂 BDA-366 对抗人类肺癌的体内测试表明，在不减少血小板的情况下具有有效功效[2]。

BDA-366 是一种有效的、选择性的 Bcl2-BH4 结构域小分子拮抗剂，它以高亲和力和选择性与 BH4 结合。 Bcl2 的抗凋亡功能依赖于 BH4 结构域，使其成为一个有前景的抗癌靶点。当 BDA-366 引起构象变化，暴露 BH3 结构域时，BCL2 的促生存功能丧失，将 BCL2 转变为促死亡蛋白。 BDA-366 在非小细胞肺癌 (NSCLC) 和小细胞肺癌 (SCLC) 细胞中以高亲和力与 BCL2 结合。通过以 BCL2 依赖性方式激活 BAX 并释放细胞色素 c，BDA-366 诱导细胞凋亡。 BDA-366 降低 H460 细胞中 Bcl2/IP3R 的结合，从而导致 Ca2+ 释放增加。

BDA366 以逐渐升高的浓度（0、0.1、0.25、0.5μM）应用于人 MM 细胞系 RPMI8226 和 U266 48 小时。收集后，用膜联蛋白V和PI对细胞进行染色，然后使用FACS进行分析。在膜联蛋白 V 阳性细胞群中，对凋亡细胞进行门控。早期凋亡细胞为Annexin V+PI+，晚期凋亡细胞为Annexin+PI+，坏死细胞为AnnexinPI+。

[1]. Oncotarget . 2016 May 10;7(19):27753-63

[2]. Cancer Cell . 2015 Jun 8;27(6):852-63.

C24H29N3O4

423.5

454.24024751

1821496-27-8

CCN(CC)C[C@H](CNC1=C2C(=C(C=C1)NC[C@H]3CO3)C(=O)C4=CC=CC=C4C2=O)O

JYOOEVFJWLBLKF-HOTGVXAUSA-N

InChI=1S/C24H29N3O4/c1-3-27(4-2)13-15(28)11-25-19-9-10-20(26-12-16-14-31-16)22-21(19)23(29)17-7-5-6-8-18(17)24(22)30/h5-10,15-16,25-26,28H,3-4,11-14H2,1-2H3/t15-,16-/m0/s1

1-[[(2S)-3-(diethylamino)-2-hydroxypropyl]amino]-4-[[(2S)-oxiran-2-yl]methylamino]anthracene-9,10-dione

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
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。