HIV protease (Ki = 2.66 nM)

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。

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%）中于 37 °C 孵育聚乙二醇 8000），有或没有阿扎那韦，以计算每种 Prt 抑制剂的抑制常数 (Ki)。使用 Cytoflor 4000，以 340 nM 激发后 490 nM 荧光发射的增加来测量底物的裂解。在五种不同浓度的阿扎那韦（1.25 nM 至 25 nM）中，使用 1.36 μM、1.66 μM、2.1 μM、3.0 μM、5.0 μM 或 15 μM 的底物进行反应。在半小时内，每五分钟观察一次底物裂解。然后，在反应的早期阶段，计算每个样品的裂解率，并根据随后的 Michaelis-Menten 图的斜率确定 Ki 值。

为了评估细胞毒性，将宿主细胞与连续稀释的阿扎那韦一起培养六天。然后使用 XTT[2,3-双(2-甲氧基-4-硝基-5-磺基苯基-2H-四唑鎓-5-甲酰苯胺)]测定法测量细胞活力，产生 50% 细胞毒性浓度 (CC50s)。为了评估人血清蛋白如何影响抗病毒活性，将 40% 成人血清或 1 mg α1-酸性糖蛋白/mL 添加到通常用于检测的 10% 胎牛血清中。

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Amounts of atazanavir in milk appear to be low based on limited data. The combination product, which also contains the CYP3A inhibitor cobicistat, has not been studied during breastfeeding, but would be expected to have similar or greater levels of atazanavir in milk. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

[1]. Antimicrob Agents Chemother . 2000 Aug;44(8):2093-9.

[2]. Drug Metab Dispos . 2005 Nov;33(11):1729-39.

[3]. Cancer Res . 2007 Nov 15;67(22):10920-8.

[4]. Mol Pharmacol . 2005 Jun;67(6):1909-19.

[5]. Drug Metab Dispos . 2005 Jun;33(6):764-70.

Atazanavir (brand name: Reyataz) is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults and children. Atazanavir comes in two different dosage forms: capsules and oral powder.
Atazanavir capsules are approved for use in adults and children 6 years of age and older who weigh at least 33 lb (15 kg). Atazanavir capsules may be used with a pharmacokinetic enhancer (boosting agent) – either ritonavir (brand name: Norvir) or cobicistat (brand name: Tybost). (A fixed-dose combination tablet containing atazanavir and cobicistat [brand name: Evotaz] is also available.)
Atazanavir oral powder is approved for use in children 3 months of age and older who weigh at least 11 lb (5 kg) and must be used with the boosting agent ritonavir.
Atazanavir is always used in combination with other HIV medicines.
Atazanavir Sulfate is a sulfate salt form of atazanavir, an aza-dipeptide analogue with a bis-aryl substituent on the (hydroxethyl)hydrazine moiety with activity against both wild type and mutant forms of HIV protease. Atazanavir does not elevate serum lipids, a common problem with other protease inhibitors.
An azapeptide and HIV-PROTEASE INHIBITOR that is used in the treatment of HIV INFECTIONS and AIDS in combination with other ANTI-HIV AGENTS.
See also: Atazanavir (has active moiety); Atazanavir sulfate; ritonavir (component of); Atazanavir sulfate; cobicistat (component of) ... View More ...

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Drug Indication
Reyataz capsules, co-administered with low dose ritonavir, are indicated for the treatment of HIV-1 infected adults and paediatric patients 6 years of age and older in combination with other antiretroviral medicinal products (see section 4. 2). Based on available virological and clinical data from adult patients, no benefit is expected in patients with strains resistant to multiple protease inhibitors (≥ 4 PI mutations). The choice of Reyataz in treatment experienced adult and paediatric patients should be based on individual viral resistance testing and the patient's treatment history (see sections 4. 4 and 5. 1). Reyataz oral powder, co-administered with low dose ritonavir, is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected paediatric patients at least 3 months of age and weighing at least 5 kg (see section 4. 2). Based on available virological and clinical data from adult patients, no benefit is expected in patients with strains resistant to multiple protease inhibitors ( 4 PI mutations). The choice of Reyataz in treatment experienced adult and paediatric patients should be based on individual viral resistance testing and the patient's treatment history (see sections 4. 4 and 5. 1).
Treatment of human immunodeficiency virus (HIV-1) infection

C38H54N6O11S

802.93

802.357

C, 56.84; H, 6.78; N, 10.47; O, 21.92; S, 3.99

229975-97-7

Atazanavir;198904-31-3

158550

White to light yellow solid powder

1.164g/cm3

995.5ºC at 760 mmHg

195.0°, or acetone; mp 198-199° (dec)

555.8ºC

0mmHg at 25°C

6.203

254.2

7

13

18

56

1190

4

S(=O)(=O)(O[H])O[H].O([H])[C@@]([H])(C([H])([H])N(C([H])([H])C1C([H])=C([H])C(C2=C([H])C([H])=C([H])C([H])=N2)=C([H])C=1[H])N([H])C([C@]([H])(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])[H])=O)[C@]([H])(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])N([H])C([C@]([H])(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])[H])=O

DQSGVVGOPRWTKI-QVFAWCHISA-N

InChI=1S/C38H52N6O7.H2O4S/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;1-5(2,3)4/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47);(H2,1,2,3,4)/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;sulfuric acid

Atazanavir sulfate; BMS-232632; BMS 232632; BMS232632

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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: ≥ 2.5 mg/mL (3.11 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，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (3.11 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，若需制备1 mL的工作液，可将 100 μL 25.0 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: ≥ 2.5 mg/mL (3.11 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 25.0 mg/mL 澄清 DMSO 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 (3.11 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 (3.11 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。
*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 6 中的溶解度: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL

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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。