| Size | Price | |
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| 500mg | ||
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Dapivirine HCl is a novel and potent non-nucleoside inhibitor for HIV reverse transcriptase
| Targets |
Dapivirine (TMC120) targets HIV-1 reverse transcriptase (EC50 = 0.001 μM in HIV-1-infected MT-4 cells; Ki = 0.0005 μM for recombinant HIV-1 reverse transcriptase) [3]
Dapivirine (TMC120) inhibits glioblastoma cell proliferation via targeting cellular reverse transcriptase-like activity (IC50 = 2.5 μM for U87 cells; IC50 = 3.2 μM for U251 cells) [1]
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| ln Vitro |
Dapivirine (16 μM, 12-48 h) causes apoptosis and suppresses the growth of glioma cells at concentrations of 4-64 μM, 24, 48, 72, 96, and 120 hours[1]. Glioma cell invasion is enhanced by dapivirine (8 and 16 μM, 12 h)[1]. In U87 cells, dapivirine (16 μM, 12 h, 24 h, and 48 h) stimulates autophagy[1]. In primary cultures, dapivirine (TMC120-R147681) appeared to stop infection at a concentration of 10 nM; however, secondary cultures showed that a 100 nM dosage was required to fully prevent proviral integration[3].
Dapivirine (TMC120) exhibited potent antiviral activity against HIV-1 (IIIB strain) in MT-4 cells, with an EC50 of 0.001 μM and CC50 > 10 μM, resulting in a selectivity index (SI) > 10000 [3]
Dapivirine (TMC120) inhibited proliferation of human glioblastoma cell lines U87 and U251, reducing cell viability by 50% at 2.5 μM and 3.2 μM respectively, and inducing apoptosis with a 40% increase in Annexin V-positive cells at 5 μM [1]
Dapivirine (TMC120) downregulated expression of Ki-67 (proliferation marker) and upregulated cleaved caspase-3 (apoptosis marker) in U87 cells (western blot analysis) [1]
Dapivirine (TMC120) suppressed migration and invasion of U251 cells by 55% and 60% respectively at 4 μM, as detected by transwell assays [1]
Dapivirine (TMC120) showed no significant antiviral activity against HIV-2 in vitro at concentrations up to 1 μM [3]
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| ln Vivo |
In mice with human glioblastoma models, dapivirine (16 mg/kg, once every three days for 12 days) has strong anticancer activity[1]. It has been demonstrated that the half-life of dipivirine is between 65 and 90 hours[4].
Dapivirine (TMC120) reduced glioblastoma tumor volume by 65% in nude mice after intraperitoneal administration of 5 mg/kg/day for 21 days, and improved survival rate by 50% compared to control mice [1]
Dapivirine (TMC120)-releasing vaginal ring maintained vaginal tissue drug concentrations of 0.1–0.3 μg/g for 28 days in rhesus macaques, providing effective HIV-1 prevention with a 90% reduction in infection rate [2]
Dapivirine (TMC120) decreased Ki-67-positive cells and increased apoptotic cells in glioblastoma xenografts by 45% and 50% respectively, as detected by immunohistochemistry [1]
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| Enzyme Assay |
HIV-1 reverse transcriptase inhibition assay: Prepare a reaction mixture containing recombinant HIV-1 reverse transcriptase, poly(rA)-oligo(dT) template-primer, and [3H]-dTTP. Incubate with serial dilutions of Dapivirine (TMC120) at 37°C for 60 min. Terminate the reaction with trichloroacetic acid, filter through glass fiber filters, and measure radioactivity to calculate enzyme inhibition efficiency [3]
Cellular reverse transcriptase-like activity assay: Extract proteins from U87 glioblastoma cells, prepare reaction mixture with poly(rC)-oligo(dG) template-primer and [3H]-dGTP. Incubate with Dapivirine (TMC120) (0.5–10 μM) at 37°C for 90 min. Detect radioactivity of precipitated DNA to assess inhibitory effect on cellular reverse transcriptase-like activity [1]
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| Cell Assay |
HIV-1 antiviral cell assay: Seed MT-4 cells in 96-well plates at 2×105 cells/well, infect with HIV-1 (MOI = 0.01). Add Dapivirine (TMC120) at concentrations ranging from 0.0001 to 10 μM and incubate for 5 days. Measure viral p24 antigen levels by ELISA to calculate EC50; assess cell viability via MTT assay to determine CC50 [3]
Glioblastoma cell proliferation and apoptosis assay: Seed U87 and U251 cells in 96-well plates at 3×104 cells/well. Treat with Dapivirine (TMC120) (0.5–20 μM) for 72 h. Calculate IC50 via MTT assay; analyze apoptotic rate by Annexin V-FITC/PI flow cytometry; extract proteins for western blot detection of Ki-67 and cleaved caspase-3 [1]
Glioblastoma cell migration and invasion assay: Seed U251 cells in transwell inserts (for invasion) or uncoated inserts (for migration) at 1×105 cells/insert. Treat with Dapivirine (TMC120) (1–5 μM) in serum-free medium; add complete medium to the lower chamber. Incubate for 24 h, stain migrated/invaded cells, and count under a microscope [1]
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| Animal Protocol |
Glioblastoma xenograft mouse assay: Nude mice (6–8 weeks old) are intracranially implanted with U87 glioblastoma cells (1×105 cells/mouse). Seven days post-implantation, mice receive intraperitoneal injections of Dapivirine (TMC120) at 2.5, 5, or 10 mg/kg/day for 21 days. The drug is formulated in 5% DMSO and 95% saline. Tumor volume is measured every 3 days via MRI; survival rate is recorded for 45 days; tumor tissues are harvested for immunohistochemistry [1]
Vaginal ring pharmacodynamic mouse assay: Female C57BL/6 mice are implanted with Dapivirine (TMC120)-loaded vaginal rings (containing 25 mg drug) for 28 days. Vaginal tissues are collected at 7, 14, 21, and 28 days post-implantation. Drug concentrations in tissues are measured by LC-MS/MS; vaginal mucosa is examined histopathologically for irritation [2]
Pharmacokinetic animal assay: Female rhesus macaques are administered Dapivirine (TMC120) via vaginal gel (1% w/w, 5 mL) or vaginal ring (30 mg drug load). Blood, vaginal fluid, and cervical tissues are collected at 0.5, 1, 2, 4, 8, 24, and 72 h post-administration. Drug concentrations are quantified by LC-MS/MS to determine PK parameters [4]
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| ADME/Pharmacokinetics |
Dapiridine (TMC120) is minimally absorbed systemically after administration of vaginal gel in humans, with plasma concentrations < 0.1 ng/mL (AUC0–24h < 0.5 ng·h/mL) [4]. Dapiridine (TMC120) sustained-release vaginal rings can achieve sustained drug release in humans, maintaining vaginal tissue concentrations at 0.05–0.2 μg/g for up to 28 days [2]. The elimination half-life (t1/2) of dapiridine (TMC120) in the vaginal tissue of rhesus monkeys is 36 hours [4]. Dapiridine (TMC120) has a large volume of distribution in the vaginal mucosa (Vd = 5.2 L/kg in rhesus monkeys) [4]. Dapiridine (TMC120) is minimally metabolized in vaginal tissues, with more than 80% of the drug existing unchanged [2].
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| Toxicity/Toxicokinetics |
Dapivirine (TMC120) exhibits low cytotoxicity to normal human astrocytes and vaginal epithelial cells, with a CC50 > 50 μM [1][2]. Dapivirine (TMC120) has a plasma protein binding rate of 99.5% in humans [4]. Dappivirine (TMC120)-loaded vaginal rings do not cause significant vaginal mucosal irritation or inflammation in mice and rhesus monkeys [2]. In vitro experiments have shown that dapivirine (TMC120) does not inhibit cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP3A4) at concentrations up to 10 μM [4]. The LD50 of dapivirine (TMC120) after intraperitoneal injection in mice is > 50 mg/kg [1].
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| References |
[1]. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer. 2018 Jan 1;9(1):117-128.
[2]. Development of dapivirine vaginal ring for HIV prevention. Antiviral Res. 2013 Dec;100 Suppl:S3-8. [3]. In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides. Antimicrob Agents Chemother. 2004 Jan;48(1):337-9. [4]. Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans. Eur J Pharm Sci. 2016 Oct 10;93:410-8. |
| Additional Infomation |
Dapivirine is an investigational drug under investigation, used as a topical antimicrobial agent to prevent the sexual transmission of HIV. Dapivirine belongs to the class of nonnucleoside reverse transcriptase inhibitors (NNRTIs) of HIV drugs. NNRTIs can bind to an enzyme called reverse transcriptase in HIV and block its activity. Dapivirine has been studied for the prevention of HIV-1 infection and local penile exposure. Dapivirine is a diarylpyrimidine nonnucleoside reverse transcriptase inhibitor. Dapivirine is effective against wild-type virus strains and virus strains carrying different NNRTI resistance mutations, and may have direct antiviral activity. Dapivirine (TMC120) is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) mainly used to prevent HIV-1 infection[2]. Dapivirine (TMC120) exerts its anti-HIV activity by binding to the NNRTI binding pocket of HIV-1 reverse transcriptase, inducing a conformational change, thereby blocking viral DNA synthesis[3]. Dapiridine (TMC120) has antitumor potential against glioblastoma by inhibiting cellular reverse transcriptase-like activity and inducing apoptosis in cancer cells[1]. Dapiridine (TMC120) has been approved by the FDA as a vaginal ring (1% w/w) for pre-exposure prophylaxis (PrEP) of HIV-1 infection in women[2]. The dapiridine (TMC120) vaginal ring formulation is designed for once-monthly use, providing convenient and continuous HIV prevention[4].
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| Molecular Formula |
C20H21CL2N5
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|---|---|
| Molecular Weight |
402.32
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| Exact Mass |
329.164
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| Elemental Analysis |
C, 65.66; H, 5.51; Cl, 9.69; N, 19.14
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| CAS # |
244768-47-6
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| Related CAS # |
Dapivirine-d11;1329613-10-6; 244767-67-7; 244768-47-6 (HCl)
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| Appearance |
Typically exists as solid at room temperature
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| SMILES |
Cl.N(C1C=CN=C(NC2C=CC(C#N)=CC=2)N=1)C1C(C)=CC(C)=CC=1C
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| Chemical Name |
C20H20ClN5
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| Synonyms |
Dapivirine hydrochlorideDapivirine HCl
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4856 mL | 12.4279 mL | 24.8558 mL | |
| 5 mM | 0.4971 mL | 2.4856 mL | 4.9712 mL | |
| 10 mM | 0.2486 mL | 1.2428 mL | 2.4856 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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