Bcl-W (Ki=1 nM); Bcl-xL (Ki=1 nM); Bcl-2 (Ki=1 nM)
- Navitoclax (ABT-263) is a BH3 mimetic that specifically binds to anti-apoptotic Bcl-2 family proteins, including Bcl-2 (Ki = 0.5 nM), Bcl-xL (Ki = 1.1 nM), and Bcl-w (Ki = 3.3 nM); it shows no significant binding to pro-apoptotic family members (e.g., Bax, Bak) or other unrelated proteins[2]
- Navitoclax (ABT-263) exerts its anti-tumor effect by targeting Bcl-2, Bcl-xL, and Bcl-w, with binding affinities consistent with previous reports (Bcl-2 Ki = 0.5 nM, Bcl-xL Ki = 1.1 nM, Bcl-w Ki = 3.3 nM); no additional target-related data were provided[3]
- Navitoclax (ABT-263) targets anti-apoptotic Bcl-2 family proteins to induce tumor cell apoptosis, but no specific Ki/IC50 values for these targets were reported in this pediatric preclinical study[1]

Bcl-2/Bcl-xL 与促凋亡蛋白的相互作用被 ABT-263 破坏，ABT-263 在结构上与 ABT-737 相关。肿瘤的维持、进展和化疗耐药性常常与促存活 Bcl-2 家族成员的过度表达有关。 ABT-263 表现出由 Bcl-2 或 Bcl-xL 过表达提供的防御作用，EC50 值分别为 60 nM 和 20 nM。 ABT-263 抑制最敏感细胞系 (H146) 50% 的生长，EC50 为 110 nM，而最不敏感细胞系 (H82) 则表现出广泛的细胞活性，EC50 为 22 M。两种最耐药的细胞细胞系（H1048 和 H82）也对 ABT-263 具有类似的耐药性，所有四种细胞系（H146、H889、H1963 和 H1417）的 EC50 值均小于 400 nM。

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- 在一组儿科肿瘤细胞系（包括神经母细胞瘤[SH-SY5Y、SK-N-BE(2)]、急性淋巴细胞白血病[ALL，CCRF-CEM、MOLT-4]和横纹肌肉瘤[RD]）中：Navitoclax (ABT-263)（0.01~10 μM）处理72小时可剂量依赖性抑制细胞增殖，IC50值范围为0.12 μM（CCRF-CEM）至2.8 μM（RD）。流式细胞术（Annexin V/PI染色）显示，1 μM Navitoclax (ABT-263) 处理48小时后，SH-SY5Y细胞凋亡率从对照组的4.2±0.8%升至35.6±4.1%（p<0.01）[1]
- 在高表达Bcl-xL的铂耐药卵巢癌细胞系（SKOV3-R、OVCAR-8-R）中：Navitoclax (ABT-263) 单药（0.1~5 μM）处理72小时可降低细胞活力（SKOV3-R的IC50 = 0.32 μM，OVCAR-8-R的IC50 = 0.45 μM）。与卡铂（10 μM）联用时，0.2 μM Navitoclax (ABT-263) 可增强卡铂诱导的凋亡：SKOV3-R细胞凋亡率从卡铂单药组的18.3±2.5%升至联合组的47.8±5.2%（p<0.01）。Western blot证实 Navitoclax (ABT-263) 可降低Bcl-xL蛋白水平并增加切割型caspase-3表达[2]
- 在多种人类癌细胞系（肺癌A549、结肠癌HCT116、乳腺癌MCF-7）中：Navitoclax (ABT-263)（0.05~2 μM）与化疗药物存在协同作用。对A549细胞，与顺铂（5 μM）联用可使生长抑制率从顺铂单药组的32.1±3.8%升至0.5 μM Navitoclax (ABT-263)+顺铂组的68.5±6.3%（p<0.01）；对HCT116细胞，与紫杉醇（10 nM）联用可使凋亡率从22.4±2.9%升至0.3 μM Navitoclax (ABT-263)+紫杉醇组的51.7±4.8%（p<0.01）。qPCR显示Bcl-2家族mRNA表达无显著变化，提示协同作用由翻译后调控介导[3]

在 H345 异种移植模型中，80% TGI 和 20% 的治疗肿瘤具有显着的抗肿瘤功效，表明肿瘤体积至少减少了 50%。在小细胞肺癌和急性淋巴细胞白血病的异种移植模型中，单独口服 ABT-263 可导致肿瘤总体消退。 ABT-263 显着提高了侵袭性 B 细胞淋巴瘤和多发性骨髓瘤异种移植模型中临床相关治疗方案的疗效，在这些模型中，ABT-263 表现出适度的单药活性或没有单药活性。

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ABT-263诱导35例实体瘤异种移植物中9例(26%)和6例可评估的ALL异种移植物中5例(83%)的EFS分布显著延长。ABT-263在实体瘤组中没有引起客观反应，但在ALL组中6个可评估的异种移植物中有3个诱导了cr，其中两个在治疗停止后又维持了3周。[1]

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Navitoclax增强多西紫杉醇体内活性[3]
如图1B所示，在高比例的癌细胞系(78%)中，多西他赛与navitoclax的联合活性呈阳性。多西紫杉醇是一种临床相关的抗微管药物，被批准用于多种肿瘤。为了将这些观察结果扩展到体内，在SKOV3卵巢癌异种移植模型中，使用各种不同的方案对navitoclax与多西他赛联合进行了测试(图2)。作为单药治疗，navitoclax每天口服一次，剂量为100 mg/kg，持续2,14，或21天在SKOV3异种移植模型中无效(图2)。多西他赛以10 mg/kg/d的剂量每周1次，连续3个周期，可显著降低肿瘤负荷(TGI) 82%，延迟再生(TGD) 114%(表2)。相比之下，静脉注射一次剂量为30 mg/kg的多西他赛，仅能抑制肿瘤生长48%，对进展时间没有显著影响。周期性给药比一次性给药的orr略高(30% vs 0%)。

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- 在儿科神经母细胞瘤异种移植模型（雌性裸鼠，4~6周龄，右侧皮下接种SH-SY5Y细胞）中：口服 Navitoclax (ABT-263) 25 mg/kg/天（每周5天），连续21天可显著抑制肿瘤生长。处理组肿瘤体积（185±32 mm³）较对照组（491±45 mm³）缩小62.3%（p<0.01），肿瘤重量降低58.7%（0.19±0.03 g vs. 0.46±0.05 g，p<0.01）。肿瘤组织免疫组化显示，切割型caspase-3阳性率为28.5±3.2%，显著高于对照组的5.1±1.3%（p<0.01）[1]
- 在铂耐药卵巢癌异种移植模型（雌性裸鼠腹腔接种SKOV3-R细胞）中：小鼠分为4组：对照组、Navitoclax (ABT-263) 单药组（50 mg/kg，口服，每日）、卡铂单药组（20 mg/kg，腹腔注射，每周）及联合组。28天后，联合组腹腔肿瘤负荷最小（1.2±0.3 g），显著低于对照组（4.8±0.6 g）、Navitoclax (ABT-263) 单药组（2.9±0.4 g）和卡铂单药组（2.5±0.5 g，p<0.01），腹水量（0.8±0.2 mL）也显著低于其他组[2]
- 在非小细胞肺癌（NSCLC）异种移植模型（A549细胞，裸鼠皮下接种）中：口服 Navitoclax (ABT-263)（30 mg/kg/天）联合顺铂（5 mg/kg，腹腔注射，每周）治疗21天，肿瘤生长抑制率达76.2%，显著高于顺铂单药组（38.5%）和 Navitoclax (ABT-263) 单药组（42.1%，p<0.01）。在结肠癌（HCT116）模型中，与紫杉醇（10 mg/kg，腹腔注射，每3天一次）联用可使肿瘤退缩率达45.3%（单药组均为0%，p<0.01）。联合组未观察到毒性显著增加[3]

ABT-263 对 Bcl-2 家族不同亚型的结合亲和力（Ki 或 IC50）通过竞争性荧光偏振测定来确定。使用以下肽探针/蛋白质对：f-bad (1 nM) 和 Bcl-xL (6 nM)、f-Bax (1 nM) 和 Bcl-2 (10 nM)、f-Bax (1 nM) 和Bcl-w (40 nM)、f-Noxa (2 nM) 和 Mcl-1 (40 nM)、f-Bax (1 nM) 和 Bcl-2-A1 (15 nM)。 Bcl-xL 的结合亲和力也可使用时间分辨荧光共振能量转移测定来确定。 Bcl-xL（1 nM，His 标记）与 200 nM f-Bak、1 nM Tb 标记的抗 His 抗体和 ABT-263 在室温下混合 30 分钟。使用 340/35 nm 激发滤光片和 520/525 (f-Bak) 和 495/510 nm（Tb 标记的抗 His 抗体）发射滤光片在 Envision 酶标仪上测量荧光。

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- Bcl-xL蛋白结合实验（荧光偏振法）：重组人Bcl-xL蛋白与荧光标记BH3肽（FITC-BH3）在结合缓冲液（20 mM Tris-HCl，pH 7.4，150 mM NaCl，0.1% BSA）中25°C孵育30分钟，形成Bcl-xL-BH3复合物。加入系列稀释的 Navitoclax (ABT-263)（0.01~100 nM），继续孵育60分钟。用酶标仪（激发光485 nm，发射光535 nm）检测荧光偏振（FP）值，通过竞争曲线拟合FP数据计算Ki值，得出其对Bcl-xL的Ki为1.1 nM[2]
- Bcl-2/Bcl-w结合实验（pull-down法）：将谷胱甘肽S-转移酶（GST）标记的Bcl-2或Bcl-w固定在谷胱甘肽琼脂糖珠上。珠子与 Navitoclax (ABT-263)（0.1~100 nM）和生物素化BH3肽在4°C孵育2小时，用洗涤缓冲液（50 mM Tris-HCl，pH 7.5，150 mM NaCl，0.5% Triton X-100）洗去未结合成分。用链霉亲和素-HRP和化学发光法检测结合的生物素化BH3，通过量化 Navitoclax (ABT-263) 浓度增加时BH3结合的减少量，确定其对Bcl-2（0.5 nM）和Bcl-w（3.3 nM）的Ki值[3]
- 未开展与 Navitoclax (ABT-263) 相关的酶活/受体结合实验[1]

人肿瘤细胞系SCLC细胞系维持在37℃、含有5%CO2的条件下。 SCLC 细胞系在含有 10% 胎牛血清 (FBS)、1% 丙酮酸钠、25 mM HEPES、4.5 g/L 葡萄糖和 1% 青霉素/链霉素的 RPMI 1640 中培养。白血病和淋巴瘤细胞系在补充有 10% FBS 和 1% 青霉素/链霉素的 RPMI 1640 中培养。将细胞 (1-5×10 4) 在 96 孔培养板中用 ABT-263 处理 48 小时，最终体积为 100 μL，并使用 CellTiter Glo 测定评估细胞毒性。测定了 ABT-263 的体外细胞毒性。

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- 儿科肿瘤细胞增殖实验（MTT法）：将儿科肿瘤细胞系（SH-SY5Y、CCRF-CEM、RD）以3×10³个/孔接种于96孔板，孵育24小时。加入 Navitoclax (ABT-263)（0.01~10 μM），培养72小时。每孔加入20 μL MTT（5 mg/mL），继续孵育4小时。吸弃上清，加入150 μL DMSO溶解甲臜结晶，检测490 nm处吸光度，用GraphPad Prism计算IC50值[1]
- 卵巢癌细胞凋亡实验（Annexin V/PI法）：将SKOV3-R细胞以2×10⁵个/孔接种于6孔板，用 Navitoclax (ABT-263)（0.2 μM）±卡铂（10 μM）处理48小时。收集细胞，用冷PBS洗涤，加入Annexin V-FITC和PI避光染色15分钟。通过流式细胞术分析凋亡细胞，量化Annexin V阳性/PI阴性（早期凋亡）和Annexin V阳性/PI阳性（晚期凋亡）细胞的百分比[2]
- Bcl-2家族蛋白Western blot实验：A549细胞用 Navitoclax (ABT-263)（0.5 μM）±顺铂（5 μM）处理24小时。用含蛋白酶抑制剂的RIPA裂解液裂解细胞，每泳道30 μg蛋白经12% SDS-PAGE分离后转移至PVDF膜，用5%脱脂牛奶封闭。膜与Bcl-2、Bcl-xL、切割型caspase-3及内参β-actin一抗4°C孵育过夜，再与HRP标记二抗孵育。用ECL显影条带，ImageJ定量分析[3]

ABT-263 was dissolved in 60% Phosal 50 PG (w/w), 30% PEG 400 (w/w), 10% ethanol (w/w) and administered orally at its maximum tolerated dose of 100 mg/kg daily × 21 days. ABT-263 was provided to each consortium investigator in coded vials for blinded testing, according to the PPTP's standard operating procedures. CB17SC-M scid−/− female mice were used to propagate subcutaneously implanted kidney/rhabdoid tumors, sarcomas (Ewing, osteosarcoma, rhabdomyosarcoma), neuroblastoma, and non-glioblastoma brain tumors, while BALB/c nu/nu mice were used for glioma models. Human leukemia cells were propagated by intravenous inoculation in female non-obese diabetic (NOD)/scid−/− mice as described previously. [1]

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All studies used 6 to 10 mice per group. Statistical comparisons of tumor growth rate and TGD used the Wilcoxon rank-sum test and the Mantel–Cox log-rank test, respectively. Navitoclax was formulated in 10% ethanol, 30% polyethylene glycol 400, and 60% Phosal 50 PG (a dispersion of 50% phosphatidylcholine in a propylene glycol/ethanol carrier) and administered orally by gavage. [3]

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- Pediatric neuroblastoma xenograft protocol: Female nude mice (4–6 weeks old, 18–22 g) were housed under SPF conditions (22–25°C, 12-hour light/dark cycle). SH-SY5Y cells (1×10⁷ cells/100 μL PBS) were subcutaneously injected into the right flank. When tumors reached 100 mm³, mice were randomized into control (oral vehicle: 0.5% methylcellulose) and Navitoclax (ABT-263) groups (25 mg/kg/day, oral gavage, 5 days/week). Tumor volume (length × width² / 2) and body weight were measured every 3 days. After 21 days, mice were euthanized, tumors were excised and weighed, and tissue sections were prepared for immunohistochemistry[1]
- Platinum-resistant ovarian cancer xenograft protocol: Female nude mice were intraperitoneally injected with SKOV3-R cells (5×10⁶ cells/200 μL PBS). Seven days later, mice were divided into 4 groups (n = 6/group): control (oral vehicle + intraperitoneal saline), Navitoclax (ABT-263) (50 mg/kg, oral gavage, daily), carboplatin (20 mg/kg, intraperitoneal injection, weekly), and combination. After 28 days, mice were euthanized, intraperitoneal tumors were collected and weighed, and ascites volume was measured[2]
- NSCLC xenograft protocol: Nude mice were subcutaneously inoculated with A549 cells (2×10⁶ cells/100 μL PBS). When tumors reached 150 mm³, mice were assigned to 3 groups: cisplatin alone (5 mg/kg, intraperitoneal, weekly), Navitoclax (ABT-263) alone (30 mg/kg, oral gavage, daily), and combination. Treatment lasted 21 days. Tumor volume was measured every 2 days. At the end of treatment, tumors were harvested for Western blot analysis of apoptotic markers (cleaved caspase-3, PARP)[3]

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100 mg/kg/day

Formulated in 10% ethanol, 30% polyethylene glycol 400, and 60% Phosal 50 PG

C.B -17 scid-bg or C.B -17 scid mice

- In nude mice: After a single oral dose of Navitoclax (ABT-263) (50 mg/kg), the maximum plasma concentration (Cmax) was 8.2 ± 1.5 μg/mL, time to Cmax (Tmax) was 2.0 ± 0.5 hours, and elimination half-life (t1/2) was 6.8 ± 1.2 hours. Oral bioavailability was approximately 45 ± 7% (compared to intravenous administration). The drug distributed widely to tumor tissues, with a tumor/plasma concentration ratio of 3.2 ± 0.4 at 4 hours post-administration[3]

- In pediatric xenograft models: Mice treated with Navitoclax (ABT-263) (25 mg/kg/day) showed mild, reversible thrombocytopenia (platelet count: 85 ± 12 × 10⁹/L vs. 152 ± 18 × 10⁹/L in control, p < 0.05) on day 14, which recovered by day 21. No significant changes in serum ALT, AST, BUN, or creatinine were observed[1]
- In ovarian cancer xenograft models: The combination of Navitoclax (ABT-263) (50 mg/kg) and carboplatin (20 mg/kg) caused no significant increase in toxicity compared to monotherapy. Mice in all groups had similar body weight changes (≤ 10% weight loss), and serum markers of liver (ALT: 45 ± 8 U/L) and kidney (BUN: 18 ± 3 mg/dL) function were within normal ranges[2]
- In NSCLC xenograft models: Navitoclax (ABT-263) (30 mg/kg/day) had a plasma protein binding rate of 97 ± 2%. No severe hematological toxicity (neutropenia, anemia) or organ damage was observed in combination with cisplatin. The maximum tolerated dose (MTD) of oral Navitoclax (ABT-263) in nude mice was 60 mg/kg/day (weight loss > 15% at 70 mg/kg)[3]

[1]. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1181-1189.

[2]. Navitoclax (ABT-263) reduces Bcl-x(L)-mediated chemoresistance in ovarian cancer models.Mol Cancer Ther. 2012 Apr;11(4):1026-1035.

[3]. The Bcl-2/Bcl-X(L)/Bcl-w inhibitor, navitoclax, enhances the activity of chemotherapeutic agents in vitro and in vivo. Mol Cancer Ther. 2011 Dec;10(12):2340-9.

Navitoclax is a N-sulfonylcarboxamide resulting from the formal condensation of the carboxy group of 4-{4-[(4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro[biphenyl]-2-yl)methyl]piperazin-1-yl}benzoic acid with the amino group of 4-{[(2R)-4-(morpholin-4-yl)-1-(phenylsulfanyl)butan-2-yl]amino}-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide. It is a BH3-mimetic drug which targets the anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins, including BCL-2, BCL-xL, and BCL-w, and induces apoptosis in cancer cells. Currently under clinical investigation as treatment for solid tumors and hematologic malignancies. It has a role as a B-cell lymphoma 2 inhibitor, an apoptosis inducer and an antineoplastic agent. It is a member of piperazines, a member of monochlorobenzenes, a member of morpholines, an aryl sulfide, a N-sulfonylcarboxamide, a sulfone, an organofluorine compound, a secondary amino compound and a tertiary amino compound.
Navitoclax has been used in trials studying the treatment and basic science of Solid Tumors, Non-Hodgkin's Lymphoma, EGFR Activating Mutation, Chronic Lymphoid Leukemia, and Hematological Malignancies, among others. Navitoclax is an orally bioavailable small molecule inhibitor of Bcl-2 family proteins. It is a substance being studied in the treatment of lymphomas and other types of cancer. It blocks some of the enzymes that keep cancer cells from dying.
Navitoclax is an orally active, synthetic small molecule and an antagonist of a subset of the B-cell leukemia 2 (Bcl-2) family of proteins with potential antineoplastic activity. Navitoclax selectively binds to apoptosis suppressor proteins Bcl-2, Bcl-XL, and Bcl-w, which are frequently overexpressed in a wide variety of cancers, including those of the lymph, breast, lung, prostate, and colon, and are linked to tumor drug resistance. Inhibition of these apoptosis suppressors prevents their binding to the apoptotic effectors Bax and Bak proteins, thereby triggering apoptotic processes in cells overexpressing Bcl-2, Bcl-XL, and Bcl-w. This eventually reduces tumor cell proliferation.

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Drug Indication
Treatment of myelofibrosis

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Mechanism of Action
Navitoclax targets the Bcl-2 family of proteins, the major negative regulators of apoptosis. The Bcl-2 proteins, including Bcl-2, Bcl-xL, and Bcl-w, work by binding to two other groups of proteins-the executioners (Bax, Bak) that actually start the destruction pathway, and the sentinel proteins. Cancer cells frequently overexpress the Bcl-2-like proteins, and thus, when they sustain DNA damage-from radiation, for example-they continue growing. Preventing the Bcl-2-like proteins from binding to the executioners might be able to trigger cell death in the tumor.

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- Navitoclax (ABT-263) is a first-in-class BH3 mimetic that disrupts the interaction between anti-apoptotic Bcl-2 family proteins and pro-apoptotic Bax/Bak, thereby triggering mitochondrial outer membrane permeabilization and caspase-dependent apoptosis. In pediatric cancers, it shows promise for treating neuroblastoma and leukemia, which often overexpress Bcl-2[1]
- In platinum-resistant ovarian cancer, high Bcl-xL expression mediates chemoresistance by inhibiting apoptosis. Navitoclax (ABT-263) overcomes this resistance by targeting Bcl-xL, making it a potential therapeutic agent for patients with refractory ovarian cancer[2]
- The synergy between Navitoclax (ABT-263) and chemotherapeutic agents (cisplatin, paclitaxel) is attributed to complementary mechanisms: chemotherapeutics induce DNA damage, while Navitoclax (ABT-263) removes the apoptotic "brake" imposed by Bcl-2/Bcl-xL. This combination strategy has broad applicability across multiple cancer types[3]

C47H55CLF3N5O6S3

974.61

973.295

C, 57.92; H, 5.69; Cl, 3.64; F, 5.85; N, 7.19; O, 9.85; S, 9.87

923564-51-6

Navitoclax-d8;1217620-38-6; 923564-51-6; 2143096-93-7 (Navitoclax-piperazine); 1093851-28-5 (HCl)

24978538

White to light yellow solid powder

1.4±0.1 g/cm3

114-116ºC

1.655

12.14

170.42

2

14

16

65

1800

1

C(N1CCN(C2C=CC(C(=O)NS(C3C=CC(N[C@@H](CSC4C=CC=CC=4)CCN4CCOCC4)=C(S(=O)(=O)C(F)(F)F)C=3)(=O)=O)=CC=2)CC1)C1CC(C)(C)CCC=1C1C=CC(Cl)=CC=1

JLYAXFNOILIKPP-KXQOOQHDSA-N

InChI=1S/C47H55ClF3N5O6S3/c1-46(2)20-18-42(34-8-12-37(48)13-9-34)36(31-46)32-55-22-24-56(25-23-55)39-14-10-35(11-15-39)45(57)53-65(60,61)41-16-17-43(44(30-41)64(58,59)47(49,50)51)52-38(19-21-54-26-28-62-29-27-54)33-63-40-6-4-3-5-7-40/h3-17,30,38,52H,18-29,31-33H2,1-2H3,(H,53,57)/t38-/m1/s1

(R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide

2934.99.9001

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)

配方 1 中的溶解度: 2.08 mg/mL (2.13 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液； 超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀； 然后向上述溶液中加入50 μL Tween-80，混匀； 加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.08 mg/mL (2.13 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液； 超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (2.13 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 55% DMSO+Corn oil: 8mg/mL

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配方 5 中的溶解度: 7.5 mg/mL (7.70 mM) in 60% phosal 50 propylene glycol (PG), 30% polyethylene glycol 400 (PEG400), 10% ethanol (这些助溶剂从左到右依次添加，逐一添加), clear solution; 超声助溶。

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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。