HIV-1
MMP-2

Indinavir（0-50 µM；18 小时）抑制 PBMC 中淋巴细胞周期的 G0/G1 期，并降低细胞增殖能力 [1]。
Huh7 和 SK-HEP-1 肝癌细胞的细胞体外茚地那韦（40 µM–40 nM；5 天）和 40 µM–40 nM（48 小时）分别抑制侵袭和 MMPs-2 激活[2]。

Indinavir（70 mg/kg；ig；每天一次，持续 3 周）可抑制体内肝癌细胞的生长[2]。

细胞系：PBMC（来自健康和感染 HIV 的志愿者）
浓度：0-50 µM
孵育时间：18 小时（预处理；用抗 CD3 刺激另外 48 小时）
结果：封闭抗CD3以剂量依赖性方式诱导细胞周期进程。导致淋巴细胞增殖反应的剂量依赖性减少。

Animal Model: Nude mice(s.c. into Huh7 and SK-HEP-1 cells)[2].
Dosage: 70 mg/kg
Administration: Oral gavage; once a day for 3 weeks.
Result: Compared to placebo, delayed the growth of s.c. implanted hepatocarcinoma xenografts in naked mice.

Absorption, Distribution and Excretion
Rapidly absorbed
Less than 20% of indinavir is excreted unchanged in the urine.

---

Metabolism / Metabolites
Hepatic. Seven metabolites have been identified, one glucuronide conjugate and six oxidative metabolites. In vitro studies indicate that cytochrome P-450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites.
Indinavir has known human metabolites that include 1-[4-benzyl-2-hydroxy-5-[(2-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]-5-oxopentyl]-N-tert-butyl-4-[(1-oxidopyridin-1-ium-3-yl)methyl]piperazine-2-carboxamide, N-tert-butyl-1-[2-hydroxy-5-[(2-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]-4-[(4-hydroxyphenyl)methyl]-5-oxopentyl]-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide, 1-[4-Benzyl-2-hydroxy-5-[(2-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]-5-oxopentyl]-N-tert-butylpiperazine-2-carboxamide, and 1-[4-benzyl-5-[(2,3-dihydroxy-2,3-dihydro-1H-inden-1-yl)amino]-2-hydroxy-5-oxopentyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide.

---

Biological Half-Life
1.8 (± 0.4) hours

Hepatotoxicity
Some degree of serum aminotransferase elevations occur in a high proportion of patients taking indinavir containing antiretroviral regimens. Moderate-to severe elevations in serum aminotransferase levels (>5 times the upper limit of normal) are found in 3% to 10% of patients, although rates may be higher in patients with HIV-HCV coinfection. These elevations are usually asymptomatic and self-limited and can resolve even with continuation of the medication. Indinavir therapy also causes increases in unconjugated (indirect) and total serum bilirubin that can manifest as jaundice in up to 10% of patients. These elevations are due to the inhibition of UDP glucuronyl transferase, the hepatic enzyme responsible for conjugation of bilirubin that is deficient in Gilbert syndrome. The hyperbilirubinemia is usually mild, the increases averaging 0.3-0.5 mg/dL, but can be more marked in patients with Gilbert syndrome with increases of 1.5 mg/dL or more and clinical jaundice. The jaundice, however, is not indicative of hepatic injury. Clinically apparent acute liver injury due to indinavir is rare. The few cases that have been reported have arisen after 1 to 8 weeks of starting indinavir, and the pattern of serum enzyme elevations has varied from hepatocellular to cholestatic. Signs of hypersensitivity (fever, rash, eosinophilia) are rare as is autoantibody formation. The acute liver injury due to indinavir is usually self-limited, but it can be severe, and isolated cases of acute liver failure have been reported. In addition, initiation of indinavir based highly active antiretroviral therapy can lead to exacerbation of an underlying chronic hepatitis B or C in coinfected individuals, typically arising 2 to 12 months after starting therapy and associated with a hepatocellular pattern of serum enzyme elevations and increases in serum levels of hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA. Indinavir therapy has not been clearly linked to lactic acidosis and acute fatty liver that is reported in association with several nucleoside analogue reverse transcriptase inhibitors.
Likelihood score: C (frequent cause of serum bilirubin elevations and probable cause of rare instances of clinically apparent liver injury).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Indinavir is no longer marketed in the US. Published experience with indinavir during breastfeeding is limited, but some infants may achieve high levels of the drug in breastmilk. Indinavir is not a recommended agent during breastfeeding. 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.

---

Protein Binding
60%

[1]. The HIV protease inhibitor Indinavir inhibits cell-cycle progression in vitro in lymphocytes of HIV-infected and uninfected individuals. Blood. 2001 Jul 15;98(2):383-9.

[2]. Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma. Clin Cancer Res. 2006 Apr 15;12(8):2634-9.

[3]. Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. J Mol Biol. 2005 Dec 9;354(4):789-800.

[4]. A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel Med Infect Dis. 2020 May-Jun;35:101646.

Indinavir is a N-(2-hydroxyethyl)piperazine, a piperazinecarboxamide and a dicarboxylic acid diamide. It has a role as a HIV protease inhibitor.
Indinavir anhydrous is a Protease Inhibitor. The mechanism of action of indinavir anhydrous is as a HIV Protease Inhibitor, and Cytochrome P450 3A4 Inhibitor.
Indinavir is an antiretroviral protease inhibitor used in the therapy and prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Indinavir can cause transient and usually asymptomatic elevations in serum aminotransferase levels and mild elevations in indirect bilirubin concentration. Indinavir is a rare cause of clinically apparent, acute liver injury. In HBV or HCV coinfected patients, antiretroviral therapy with indinavir may result in an exacerbation of the underlying chronic hepatitis B or C.
Indinavir has been reported in Streptomyces with data available.
Indinavir is a synthetic hydroxyaminopentane amide agent that selectively inhibits the protease of both human immunodeficiency virus 1 and 2. The incorporation of a basic amine into the hydroxyethylene backbone improves its aqueous solubility and its oral bioavailability.
Indinavir Anhydrous is an anhydrous formulation of indinavir, a synthetic hydroxyaminopentane amide agent that selectively inhibits the protease of both human immunodeficiency virus 1 and 2. The incorporation of a basic amine into the hydroxyethylene backbone improves its aqueous solubility and its oral bioavailability.
A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.

---

Drug Indication
Indinavir is an antiretroviral drug for the treatment of HIV infection.
FDA Label
Crixivan is indicated in combination with antiretroviral nucleoside analogues for the treatment of HIV-1 infected adults. ,

---

Mechanism of Action
Indinavir inhibits the HIV viral protease enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

---

Pharmacodynamics
Indinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Indinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

C36H47N5O4

613.79

613.362

C, 70.45; H, 7.72; N, 11.41; O, 10.43

150378-17-9

Indinavir sulfate;157810-81-6;Indinavir sulfate ethanolate;2563866-80-6;Indinavir-d6;185897-02-3

5362440

Solid powder

1.2±0.1 g/cm3

831.6±75.0 °C at 760 mmHg

150-153ºC

456.8±37.1 °C

0.0±3.2 mmHg at 25°C

1.629

4.04

118.03

4

7

12

45

952

5

O=C([C@@H](C[C@H](O)CN(CCN(CC1=CN=CC=C1)C2)[C@@H]2C(NC(C)(C)C)=O)CC3=CC=CC=C3)N[C@H]4C(C=CC=C5)=C5C[C@H]4O

CBVCZFGXHXORBI-PXQQMZJSSA-N

InChI=1S/C36H47N5O4/c1-36(2,3)39-35(45)31-24-40(22-26-12-9-15-37-21-26)16-17-41(31)23-29(42)19-28(18-25-10-5-4-6-11-25)34(44)38-33-30-14-8-7-13-27(30)20-32(33)43/h4-15,21,28-29,31-33,42-43H,16-20,22-24H2,1-3H3,(H,38,44)(H,39,45)/t28-,29+,31+,32-,33+/m1/s1

(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide

trade name: Crixivan; DRG-0233; L-735 524; DRG0233; MK-639; L 735 524; MK 639; DRG 233; L735 524; MK639;

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)

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。