NF-κB; 20S proteasome (Ki = 0.6 nM)

体外活性：硼替佐米是一种硼酸二肽，是 26S 蛋白酶体的高选择性、可逆抑制剂，其主要功能是降解错误折叠的蛋白质，对于细胞周期的调节至关重要。研究表明，接触硼替佐米可以稳定 p21、p27 和 p53，以及促凋亡 Bid 和 Bax 蛋白、caveolin-1 和抑制剂 κB-α，从而防止核因子 κB 诱导的细胞存活途径的激活。 Bortezomib 还促进促凋亡 c-Jun-NH2 末端激酶的激活以及内质网应激反应。这些细胞蛋白水平的改变会抑制癌细胞的增殖、迁移和促进细胞凋亡。硼替佐米可渗透到细胞中，抑制蛋白酶体介导的长寿命蛋白质的细胞内蛋白水解，浓度约为 0.1 μM，可抑制 50% 的蛋白水解。在来自美国国家癌症研究所 (NCI) 的多种人类肿瘤的整个 60 个癌细胞系中，硼替佐米的 50% 平均生长抑制值为 7 nM。用 Bortezomib (100 nM) 处理 PC-3 细胞 8 小时，导致 G2-M 细胞积累，G1 细胞数量相应减少。 Bortezomib 在 24 小时和 48 小时杀死 PC-3 细胞，IC50 分别为 100 和 20 nM。硼替佐米在治疗后 16-24 小时诱导核凝结。 Bortezomib 处理导致 PARP 以时间依赖性方式裂解，浓度低至 100 nM 在 24 小时内有效。激酶测定：典型的动力学运行，将 2.00 mL 测定缓冲液（20 mM HEPES、0.5 mM EDTA、0.035% SDS、pH 7.8）和 DMSO 中的 Suc-Leu-Leu-Val-Tyr-AMC 添加到 3 mL 荧光管中比色皿，将比色皿置于荧光分光光度计的带夹套的比色池支架中。通过循环水浴将反应温度维持在37℃。反应液达到热平衡后（5分钟），将1 μL−10 μL酶原液加入比色皿中。通过伴随 AMC 从肽-AMC 底物上裂解而产生的 440 nm (λex= 380 nm) 荧光发射的增加来监测反应进度。细胞测定：通过测量细胞的MTT染料吸光度来评估硼替佐米对细胞生长的抑制作用。在 48 小时培养的最后 4 小时，将来自 48 小时培养的细胞（人多发性骨髓瘤细胞系 U266）用 10 µL 5 mg/mL MTT 脉冲到每个孔中，然后加入 100 µL 含有 0.04 N HCl 的异丙醇。使用分光光度计在 570 nm 处测量吸光度。

硼替佐米作为单药的抗癌作用已在多发性骨髓瘤、成人 T 细胞白血病、肺癌、乳腺癌、前列腺癌、胰腺癌、头颈癌、结肠癌以及黑色素瘤的异种移植模型中得到证实。每天口服硼替佐米 1.0 mg/kg，持续 18 天会导致肿瘤生长延迟，并减少 Lewis 肺癌模型中的转移数量。单剂量高达 5 mg/kg 的硼替佐米显着降低了乳腺肿瘤细胞的存活率。在前列腺癌小鼠异种移植模型中，每周给予硼替佐米 1.0 mg/kg，持续 4 周，可使肿瘤生长减少 60%。 1.0 mg/kg Bortezomib 给药 4 周可导致胰腺癌小鼠异种移植物生长减少 72% 或 84%，并增加肿瘤细胞凋亡。 1.0 mg/kg Bortezomib 治疗可显着抑制人浆细胞瘤异种移植物的生长，增加肿瘤细胞凋亡和总体存活率，并减少肿瘤血管生成。

在典型的动力学运行中，将 DMSO 中的 Suc-Leu-Leu-Val-Tyr-AMC 和 2.00 mL 测定缓冲液（20 mM HEPES、0.5 mM EDTA、0.035% SDS，pH 7.8）添加到 3 mL 荧光比色皿中。然后将比色皿放置在荧光分光光度计的带夹套的样品池支架中。循环水浴将反应温度保持在37°C。一旦反应溶液达到热平衡，就将一微升到十微升的储备酶溶液添加到比色皿中，这需要五分钟。当 AMC 从肽-AMC 底物上裂解时，在 440 nm (λex= 380 nm) 处荧光发射的程度增加表明反应的进展情况。

细胞的MTT染料吸光度用于测量硼替佐米对细胞生长的抑制作用。在 48 小时培养的最后 4 小时，每孔中用 10 μL 5 mg/mL MTT 脉冲细胞。随后加入 100 μL 含有 0.04 N HCl 的异丙醇。用分光光度计在 570 nm 处测定吸光度。

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硼替佐米预处理使多发性骨髓瘤、髓性白血病和肾癌细胞敏感，但对TRAIL/ apo2l诱导的细胞凋亡没有作用。在体内实验中，将骨髓和肾癌细胞混合物（含或不含硼替佐米和/或TRAIL/Apo2L）移植到小鼠骨髓中。所有接受TRAIL/Apo2L治疗的小鼠在35天内死于白血病，而接受硼替佐米治疗的小鼠中有50%的细胞存活超过100天，而同时接受TRAIL/Apo2L和硼替佐米治疗的小鼠中有90%的细胞存活超过100天。[2]
硼替佐米通过抑制NF-κB，不仅促进癌细胞凋亡，而且使这些细胞对化疗、放疗或免疫治疗敏感。然而，由于仅通过PS-1145特异性抑制NF-κB只能部分抑制肿瘤细胞的增殖，硼替佐米的细胞毒活性还必须依赖于对其他信号转导途径靶点的改变调节。[2]
有趣的是，对蛋白酶体抑制的敏感性部分依赖于体外乳腺癌和肺癌的p53状态，但硼替佐米诱导的凋亡和/或化疗增敏在前列腺、多发性骨髓瘤和结肠癌细胞中是p53独立的。因此，与p53状态相关的硼替佐米敏感性的变化程度似乎依赖于细胞类型。[2]
最近发表的一项研究发现，硼替佐米可阻止多发性骨髓瘤细胞中caveolin-1的活化。[2]

Human plasmacytoma xenografts RPMI 8226
1 mg/kg
i.v. twice weekly for 4 weeks, then once weekly

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Following weekly i.v. treatment of PS-341 to mice bearing the PC-3 tumor, a significant decrease (60%) in tumor burden was observed in vivo. Direct injection of PS-341 into the tumor also caused a substantial (70%) decrease in tumor volume with 40% of the drug-treated mice having no detectable tumors at the end of the study. Studies also revealed that i.v. administration of PS-341 resulted in a rapid and widespread distribution of PS-341, with highest levels identified in the liver and gastrointestinal tract and lowest levels in the skin and muscle. Modest levels were found in the prostate, whereas there was no apparent penetration of the central nervous system. An assay to follow the biological activity of the PS-341 was established and used to determine temporal drug activity as well as its ability to penetrate tissues. As such, PS-341 was shown to penetrate PC-3 tumors and inhibit intracellular proteasome activity 1.0 h after i.v. dosing. These data illustrate that PS-341 not only reaches its biological target but has a direct effect on its biochemical target, the proteasome. Importantly, the data show that inhibition of this target site by PS-341 results in reduced tumor growth in murine tumor models. Together, the results highlight that the proteasome is a novel biochemical target and that inhibitors such as PS-341 represent a unique class of antitumor agents. PS-341 is currently under clinical evaluation for advanced cancers.[1]

Absorption, Distribution and Excretion
Following intravenous administration of 1 mg/m2 and 1.3 mg/m2 doses, the mean Cmax of bortezomib were 57 and 112 ng/mL, respectively. In a twice-weekly dosing regimen, the Cmax ranged from 67 to 106 ng/mL at the dose of 1 mg/m2 and 89 to 120 ng/mL for the 1.3 mg/m2 dose. In patients with multiple myeloma, the Cmax of bortezomib followig subcutaneous administration was lower than that of intravenously-administered dose; however, the total systemic exposure of the drug was equivalent for both routes of administration. There is a wide interpatient variability in drug plasma concentrations.
Bortezomib is eliminated by both renal and hepatic routes.
The mean distribution volume of bortezomib ranged from approximately 498 to 1884 L/m² in patients with multiple myeloma receiving a single- or repeat-dose of 1 mg/m² or 1.3 mg/m². Bortezomib distributes into nearly all tissues, except for the adipose and brain tissue.
Following the administration of a first dose of 1 mg/m² and 1.3 mg/m², the mean mean total body clearances were 102 and 112 L/h, respectively. The clearances were 15 and 32 L/h after the subsequent dose of 1 and 1.3 mg/m², respectively.
Following intravenous administration of 1 mg/sq m and 1.3 mg/sq m doses to 24 patients with multiple myeloma (n=12, per each dose level), the mean maximum plasma concentrations of bortezomib (Cmax) after the first dose (Day 1) were 57 and 112 ng/mL, respectively.
In subsequent doses, when administered twice weekly, the mean maximum observed plasma concentrations ranged from 67 to 106 ng/mL for the 1 mg/sq m dose and 89 to 120 ng/mL for the 1.3 mg/sq m dose. The mean elimination half-life of bortezomib upon multiple dosing ranged from 40 to 193 hours after the 1 mg/sq m dose and 76 to 108 hours after the 1.3 mg/sq m dose. The mean total body clearances was 102 and 112 L/hr following the first dose for doses of 1 mg/sq m and 1.3 mg/sq m, respectively, and ranged from 15 to 32 L/hr following subsequent doses for doses of 1 and 1.3 mg/sq m, respectively.
The mean distribution volume of bortezomib ranged from approximately 498 to 1884 L/sq m following single- or repeat-dose administration of 1 mg/sq m or 1.3mg/sq m to patients with multiple myeloma. This suggests bortezomib distributes widely to peripheral tissues. The binding of bortezomib to human plasma proteins averaged 83% over the concentration range of 100 to 1000 ng/mL.
It is not known whether bortezomib is excreted in human milk.
For more Absorption, Distribution and Excretion (Complete) data for BORTEZOMIB (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Bortezomib is primarily metabolized by CYP3A4, CYP2C19, and CYP1A2. CYP2D6 and CYP2C9 are also involved in drug metabolism, but to a smaller extent. Oxidative deboronation, which involves the removal of boronic acid from the parent compound, is the main metabolic pathway. Metabolites of bortezomib are pharmacologically inactive and more than 30 metabolites have been identified in human and animal studies.
In vitro studies with human liver microsomes and human cDNA-expressed cytochrome P450 isozymes indicate that bortezomib is primarily oxidatively metabolized via cytochrome P450 enzymes 3A4, 2C19, and 1A2. Bortezomib metabolism by CYP 2D6 and 2C9 enzymes is minor. The major metabolic pathway is deboronation to form 2 deboronated metabolites that subsequently undergo hydroxylation to several metabolites. Deboronated bortezomib metabolites are inactive as 26S proteasome inhibitors. Pooled plasma data from 8 patients at 10 min and 30 min after dosing indicate that the plasma levels of metabolites are low compared to the parent drug.
... The P450 inhibition potential of bortezomib and its major deboronated metabolites M1 and M2 and their dealkylated metabolites M3 and M4 was evaluated in human liver microsomes for the major P450 isoforms 1A2, 2C9, 2C19, 2D6, and 3A4/5. Bortezomib, M1, and M2 were found to be mild inhibitors of CYP2C19 (IC(50) approximately 18.0, 10.0, and 13.2 microM, respectively), and M1 was also a mild inhibitor of CYP2C9 (IC(50) approximately 11.5 microM). However, bortezomib, M1, M2, M3, and M4 did not inhibit other P450s (IC(50) values > 30 microM). There also was no time-dependent inhibition of CYP3A4/5 by bortezomib or its major metabolites. ...
... Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. ...

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Biological Half-Life
The mean elimination half-life of bortezomib ranged from 40 to 193 hours following a multiple dosing regimen at a 1 mg/m² dose. The half-life ranged from 76 to 108 hours after multiple dosing of 1.3 mg/m² bortezomib.
The mean elimination half-life of bortezomib upon multiple dosing ranged from 40 to 193 hours after the 1 mg/sq m dose and 76 to 108 hours after the 1.3 mg/sq m dose.

Hepatotoxicity
In large clinical trials of bortezomib, elevations in serum aminotransferase levels were common, occurring in ~10% of patients. However, values greater than 5 times the upper limit of normal (ULN) were rare, occurring in
Bortezomib is typically given with other chemotherapeutic agents including cyclophosphamide and dexamethasone which can cause reactivation of hepatitis B. However, there have been no reports of reactivation of hepatitis B specifically attributable to bortezomib alone.
Likelihood score: C (probable cause of clinically apparent drug induced liver injury).

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Protein Binding
Over the concentration range of 100 to 1000 ng/mL, bortezomib is about 83% bound to human plasma proteins.

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Interactions
Hypoglycemia and hyperglycemia have been reported in patients with diabetes mellitus who received bortezomib concomitantly with oral antidiabetic agents. If bortezomib is used concomitantly with oral antidiabetic agents, blood glucose concentrations should be monitored carefully and dosage of the antidiabetic agent adjusted as necessary.
Potential interaction (increased risk of peripheral neuropathy) when bortezomib is used concomitantly with other drugs associated with peripheral neuropathy (eg, amiodarone, antiviral agents, isoniazid, nitrofurantoin, hydroxymethylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors [statins]).
Potential interaction (increased risk of hypotension) when bortezomib is used with drugs that can cause hypotension. Dosage adjustment of hypotensive agents may be necessary.
... In a preclinical toxicology study, bortezomib-treated rats resulted in liver enlargement (35%). Ex vivo analyses of the liver samples showed an 18% decrease in cytochrome P450 (P450) content, a 60% increase in palmitoyl coenzyme A beta-oxidation activity, and a 41 and 23% decrease in CYP3A protein expression and activity, respectively. Furthermore, liver samples of bortezomib-treated rats had little change in CYP2B and CYP4A protein levels and activities. To address the likelihood of clinical drug-drug interactions, the P450 inhibition potential of bortezomib and its major deboronated metabolites M1 and M2 and their dealkylated metabolites M3 and M4 was evaluated in human liver microsomes for the major P450 isoforms 1A2, 2C9, 2C19, 2D6, and 3A4/5. Bortezomib, M1, and M2 were found to be mild inhibitors of CYP2C19 (IC(50) approximately 18.0, 10.0, and 13.2 microM, respectively), and M1 was also a mild inhibitor of CYP2C9 (IC(50) approximately 11.5 microM). However, bortezomib, M1, M2, M3, and M4 did not inhibit other P450s (IC(50) values > 30 microM). There also was no time-dependent inhibition of CYP3A4/5 by bortezomib or its major metabolites. Based on these results, no major P450-mediated clinical drug-drug interactions are anticipated for bortezomib or its major metabolites. ...

[1]. Cancer Res . 1999 Jun 1;59(11):2615-22.

[2]. Cancer Cell Int . 2005 Jun 1;5(1):18.

[3]. Cancer Res . 2002 Sep 1;62(17):4996-5000.

[4]. Biochemistry . 1996 Apr 2;35(13):3899-908.

[5]. Cancer Res . 2001 Apr 1;61(7):3071-6.

[6]. Am J Cancer Res . 2011;1(7):913-24. Epub 2011 Aug 23.

Therapeutic Uses
Antineoplastic Agents; Protease Inhibitors
Bortezomib injection is indicated for the treatment of patients with multiple myeloma who have received at least 1 prior therapy. /Included in US product label/
Bortezomib injection is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy. /Included in US product label/

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Drug Warnings
Known hypersensitivity to bortezomib, boron, or mannitol.
Bortezomib mainly causes sensory peripheral neuropathy, but severe motor peripheral neuropathy also has been reported. In the phase III trial, peripheral neuropathy occurred in 36% of patients receiving bortezomib and 9% of patients receiving dexamethasone. Grade 3 or 4 peripheral neuropathy occurred in 7 or less than 1%, respectively, of patients receiving bortezomib. Following dosage adjustments, amelioration or resolution of peripheral neuropathy was reported in 51% of patients with grade 2 or higher peripheral neuropathy within a median of 3.5 months from onset. About 8% of patients discontinued bortezomib therapy because of peripheral neuropathy.
Patients receiving bortezomib should be monitored for manifestations of neuropathy (eg, burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain). Dose and/or frequency of administration of bortezomib should be adjusted in patients who experience new-onset or exacerbation of peripheral neuropathy.
In the phase III trial, asthenia (ie, fatigue, malaise, weakness) was reported in 61% of patients receiving bortezomib and 45% of patients receiving dexamethasone. Grade 3 asthenia occurred in 12 versus 6%, respectively, of patients receiving bortezomib or dexamethasone. About 3% of patients receiving bortezomib and 2% of patients receiving dexamethasone discontinued therapy because of asthenia.
For more Drug Warnings (Complete) data for BORTEZOMIB (26 total), please visit the HSDB record page.

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Pharmacodynamics
Bortezomib works to target the ubiquitin-proteasome pathway, an essential molecular pathway that regulates intracellular concentrations of proteins and promotes protein degradation. The ubiquitin-proteasome pathway is often dysregulated in pathological conditions, leading to aberrant pathway signalling and the formation of malignant cells. In one study, patient-derived chronic lymphocytic leukemia (CLL) cells contained 3-fold higher levels of chymotrypsin-like proteasome activity than normal lymphocytes. By reversibly inhibiting proteasome, bortezomib prevents proteasome-mediated proteolysis. Bortezomib exerts a cytotoxic effect on various cancer cell types _in vitro_ and delays tumour growth _in vivo_ in nonclinical tumour models. Bortezomib inhibits the proteasome activity in a dose-dependent manner. In one pharmacodynamic study, more than 75% of proteasome inhibition was observed in whole blood samples within one hour after dosing of bortezomib.

C19H25BN4O4

384.24

384.196

C, 59.39; H, 6.56; B, 2.81; N, 14.58; O, 16.66

179324-69-7

Bortezomib-d8

387447

White solid powder

1.2±0.1 g/cm3

122-124°C

1.564

2.45

124.44

4

6

9

28

500

2

CC(C[C@H](NC([C@@H](NC(C1=CN=CC=N1)=O)CC1=CC=CC=C1)=O)B(O)O)C

GXJABQQUPOEUTA-RDJZCZTQSA-N

InChI=1S/C19H25BN4O4/c1-13(2)10-17(20(27)28)24-18(25)15(11-14-6-4-3-5-7-14)23-19(26)16-12-21-8-9-22-16/h3-9,12-13,15,17,27-28H,10-11H2,1-2H3,(H,23,26)(H,24,25)/t15-,17-/m0/s1

[(1R)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid

NSC 681239; PS-341; PS341; MLN-341; PS 341; LDP-341; LDP 341; LDP341; MLN341; PS-341; Bortezomib (PS-341); Ps 341; Bortezomib accord; MLN 341. Brand name: VELCADE

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

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: ≥ 4 mg/mL (10.41 mM) (饱和度未知) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (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 40.0 mg/mL 澄清 EtOH 储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入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: ≥ 4 mg/mL (10.41 mM) (饱和度未知) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (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 40.0mg/mL澄清EtOH储备液加入到900μL 20％SBE-β-CD生理盐水中，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: ≥ 4 mg/mL (10.41 mM) (饱和度未知) in 10% EtOH + 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 40.0 mg/mL 澄清乙醇储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: ≥ 2.5 mg/mL (6.51 mM) (饱和度未知) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*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 5 中的溶解度: ≥ 2.5 mg/mL (6.51 mM) (饱和度未知) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。

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配方 6 中的溶解度: ≥ 2.08 mg/mL (5.41 mM) (饱和度未知) 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), 澄清溶液。
例如，若需制备1 mL的工作液，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 7 中的溶解度: ≥ 2.08 mg/mL (5.41 mM) (饱和度未知) 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), 澄清溶液。
例如，要配制1 mL工作液，可将100 μL 20.8 mg/mL的澄清DMSO储备液加入到900 μL 20% SBE-β-CD生理盐水溶液中， 混合均匀。
*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 8 中的溶解度: ≥ 2.08 mg/mL (5.41 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，要配制1 mL工作液，可将100 μL 20.8 mg/mL 澄清DMSO 储备液加入900 μL 玉米油中，混匀。

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配方 9 中的溶解度: ≥ 0.5 mg/mL (1.30 mM) (饱和度未知) in 1% DMSO 99% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。

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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。