在 H9 和 PBMC 细胞中，剂量大于 100 μM 的地拉韦啶具有 50% 的细胞毒性。在 100 μM 浓度下，地拉韦啶具有最小的细胞毒性，导致外周血淋巴细胞活力降低不到 8% [1]。 Delavirdine 对野生型 HIV-1 逆转录酶 (RT) 的 IC50 值为 0.26 μM，对 Y181C 取代和 K103N 取代的 RT 的 IC50 值分别为 8.32 uM 和 7.7 uM [1]。

地拉韦啶（U 90152）（口服灌胃；10 mg/kg、200 mg/kg、250 mg/kg；单剂量）吸收消化迅速，形成微小循环成分，具有独特的药代动力学。呈线性，并且限制或抑制 CD-1 小鼠中去烷基阿维啶的代谢（PK 研究）[1]。

Absorption, Distribution and Excretion
Rapid Absorption Deraviridine is primarily converted into various inactive metabolites via cytochrome P450 3A (CYP3A). The concentration of deraviridine in the milk of lactating rats is three to five times higher than its plasma concentration. Metabolism/Metabolites Hepatic Metabolism Known human metabolites of deraviridine include N-deisopropylidene deraviridine and N-[2-[4-[6-oxo-3-(propyl-2-amino)-1H-pyridin-2-yl]piperazin-1-carbonyl]-1H-indol-5-yl]methanesulfonamide. Biological Half-Life 5.8 hours

Hepatotoxicity
In patients receiving deraviridine, elevated serum transaminases occur in 25% or more of cases, but only 4% or fewer have transaminases elevated to more than 5 times the upper limit of normal; this proportion is even higher in patients with concurrent chronic hepatitis C virus infection. Clinically significant hepatotoxicity caused by deraviridine should be rare, as there are no reported cases of hepatitis or jaundice. Nevertheless, the sponsor has received case reports of hepatitis, jaundice, and liver failure, which are mentioned in the product information leaflet. Liver injury may be immunoallergic, following a pattern similar to that caused by nevirapine and efavirenz. Immunohistotropic hepatitis caused by non-nucleoside reverse transcriptase inhibitors usually appears within 1 to 8 weeks after the start of treatment. Common symptoms of allergic reactions include rash, fever, and eosinophilia, sometimes accompanied by facial edema, lymphadenopathy, and lymphocytosis. Serum enzyme profiles may show cholestatic, hepatocellular, or mixed patterns. Recovery is rapid upon discontinuation of the drug.
Probability Score: E (Unconfirmed but suspected cause of clinically significant liver damage).

---

Protein Binding Rate
98%

[1]. U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication. Antimicrob Agents Chemother. 1993 May;37(5):1127-31.

[2]. Metabolism of the HIV-1 Reverse Transcriptase Inhibitor Delavirdine In Mice. Research Article.

Delavirdine is an amide formed by the condensation of the 4-amino group of 5-[(methanesulfonyl)amino]-1H-indole-2-carboxylic acid and 1-[3-(isopropylamino)pyridin-2-yl]piperazine. Delavirdine is a non-nucleoside reverse transcriptase inhibitor with specific activity against HIV-1. Viral resistance develops rapidly when Delavirdine is used alone; therefore, it is often used in combination with other antiretroviral drugs for the treatment of HIV infection (in the form of mesylate). It is both an HIV-1 reverse transcriptase inhibitor and an antiviral drug. It is an N-acylpiperazine, sulfonamide, aminopyridine, and indolecarboxamide compound. It is a potent non-nucleoside reverse transcriptase inhibitor with specific activity against HIV-1. Delavirdine is a non-nucleoside analog reverse transcriptase inhibitor of human immunodeficiency virus type 1. The mechanism of action of Delavirdine is as a non-nucleoside reverse transcriptase inhibitor.
Dilaviridine is a non-nucleoside reverse transcriptase inhibitor used in combination with other drugs to treat human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The incidence of transient elevations in serum transaminases during ilaviridine treatment is low, and it rarely causes clinically significant acute liver injury.
Dilaviridine is a synthetic non-nucleoside reverse transcriptase inhibitor. When used in combination with other antiretroviral drugs, it has been shown to reduce HIV viral load and increase CD4 white blood cell counts in patients. As an inhibitor of the cytochrome P450 system, ilaviridine may lead to elevated serum concentrations of co-administered protease inhibitors metabolized by the cytochrome P450 system.
A potent non-nucleoside reverse transcriptase inhibitor with specific activity against HIV-1.
See also: Dilaviridine mesylate (note moved to).

---

Drug Indications
For the treatment of HIV-1 infection in combination with an appropriate antiretroviral drug when treatment is required.
FDA Label
Mechanism of Action
Dilaviridine binds directly to viral reverse transcriptase (RT) and blocks RNA-dependent and DNA-dependent DNA polymerase activity by disrupting the enzyme's catalytic site.
Pharmacodynamics
Dilaviridine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) active against human immunodeficiency virus type 1 (HIV-1). Deilaviridine binds directly to reverse transcriptase (RT) and blocks RNA-dependent and DNA-dependent DNA polymerase activity by disrupting the enzyme's catalytic site. Deilaviridine's activity does not compete with the template or nucleoside triphosphates. HIV-2 reverse transcriptase and eukaryotic DNA polymerases (such as human DNA polymerase α, β, or σ) are not inhibited by deilaviridine.

C22H28N6O3S

456.56

456.194

136817-59-9

Delavirdine mesylate;147221-93-0

5625

White to off-white solid powder

1.388g/cm3

732ºC at 760mmHg

226-228ºC

396.5ºC

2.74E-21mmHg at 25°C

1.68

3.946

118.81

3

7

6

32

749

0

WHBIGIKBNXZKFE-UHFFFAOYSA-N

InChI=1S/C22H28N6O3S/c1-15(2)24-19-5-4-8-23-21(19)27-9-11-28(12-10-27)22(29)20-14-16-13-17(26-32(3,30)31)6-7-18(16)25-20/h4-8,13-15,24-26H,9-12H2,1-3H3

N-[2-[4-[3-(propan-2-ylamino)pyridin-2-yl]piperazine-1-carbonyl]-1H-indol-5-yl]methanesulfonamide

BHAP-U 90152; DLV; U 90152; Delavirdine; trade name Rescriptor.

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

---

注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

View More

注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

---

口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

View More

口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

---

注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

---

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。