CYP3; HIV-1

体外活性：Atazanavir 在病毒感染的 H9 细胞中抑制病毒 gag 前体 p55 多蛋白的蛋白水解裂解，IC50 约为 47 nM。 Atazanavir 在 RF/MT-2 菌株中表现出有效的抗病毒活性，EC50 为 3.89 nM。 Atazanavir 是一种胆红素葡萄糖醛酸化抑制剂，IC50 为 2.4 μM。 Atazanavir 抑制重组 UGT1A1，Ki 为 1.9 μM。 Atazanavir 抑制 U251、T98G 和 LN229 胶质母细胞瘤细胞系的细胞生长，并显着增加 GRP78 和 CHOP 蛋白水平。阿扎那韦导致 U251 胶质母细胞瘤细胞中各种不同大小的多泛素化蛋白显着增加。 Atazanavir 还抑制人 20S 蛋白酶体，IC50 为 26 μM。 Atazanavir (30 μM) 改变 HepG2 细胞中 ER 应激和 UPR 基因表达的程度。 Atazanavir (30 mM) 导致 LS180V 细胞中免疫反应性 P-gp 表达增加 2.5 倍，同时细胞内 Rh123 减少。激酶测定：为了确定每种 Prt 抑制剂的抑制常数 (Ki)，将纯化的 HIV-1 RF 野生型 Prt (2.5 nM) 与 1 μM 至 15 μM 荧光底物在反应缓冲液（1 M NaCl， 1 mM EDTA、0.1 M 乙酸钠 [pH 5.5]、0.1% 聚乙二醇 8000），存在或不存在阿扎那韦。使用 Cytoflor 4000 在 340 nM 激发后，通过测量 490 nM 荧光发射的增加来量化底物的裂解。使用 1.36 μM、1.66 μM、2.1 μM、3.0 μM、5.0 μM 或 15 μM 底物进行反应存在五种浓度的阿扎那韦（1.25 nM 至 25 nM）。以 5 分钟的间隔监测底物裂解，持续 30 分钟。然后确定每个样品在反应早期时间点的裂解率，并根据所得米氏图的斜率确定 Ki 值。细胞测定：为了确定细胞毒性，将宿主细胞在连续稀释的阿扎那韦存在下孵育 6 天，并使用 XTT[2,3-bis(2-methoxy-4-硝基-5-磺基苯基-2H-) 定量细胞活力。 tetrazolium-5-carboxanilide] 测定计算 50% 细胞毒性浓度 (CC50s)。为了评估人血清蛋白对抗病毒活性的影响，通常用于测定的 10% 胎牛血清替换为 40% 成人血清或 1 α1-酸性糖蛋白毫克/毫升。

阿扎那韦具有出色的口服生物利用度，范围为 60-70%

[1]. Atazanavir: new option for treatment of HIV infection. Clin Infect Dis. 2004 Jun 1;38(11):1599-604.

[2]. Atazanavir: its role in HIV treatment. Expert Rev Anti Infect Ther. 2008 Dec;6(6):785-96.

[3]. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212.

C38H52N6O7

704.86

704.38975

C, 64.75; H, 7.44; N, 11.92; O, 15.89

198904-31-3

Atazanavir sulfate;229975-97-7;Atazanavir-d15;1092540-56-1;Atazanavir-d18;1092540-52-7;Atazanavir-d9;1092540-51-6;Atazanavir-d5;1132747-14-8;Atazanavir-d6;1092540-50-5

Solid powder

CC(C)(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)[C@H](CN(CC2=CC=C(C=C2)C3=CC=CC=N3)NC(=O)[C@H](C(C)(C)C)NC(=O)OC)O)NC(=O)OC

AXRYRYVKAWYZBR-GASGPIRDSA-N

InChI=1S/C38H52N6O7/c1-37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47)/t29-,30-,31+,32+/m0/s1

methyl N-[(2S)-1-[2-[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoyl]amino]-4-phenylbutyl]-2-[(4-pyridin-2-ylphenyl)methyl]hydrazinyl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate

Latazanavir; Zrivada; Reyataz; BMS-232632; BMS232632; BMS 232632; Atazanavir

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)

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。