| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Dapivirine (also known as TMC120) is a potent non-nucleoside inhibitor for HIV reverse transcriptase with IC50 of 24 nM, it inhibits a broad panel of HIV-1 isolates from different classes, inclucing a wide range of NNRTI-resistant isolates. Dapivirine prevents HIV-induced syncytium formation in the nanomolar range and shows a low cytostatic activity. Dapivirine apparently blocks HIV-1 infection in the primary cultures at a 10 nM concentration, but secondary cultures reveals that a 100 nM concentration is needed to completely prevent proviral integration.
| 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] |
| 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] |
| 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] |
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: U87 glioblastoma cells. Tested Concentrations: 4, 8, 16 μM. Incubation Duration: 24, 48, 72, 96 and 120 hrs (hours). Experimental Results: Inhibited proliferation of glioma cells. IC50 was 10.73 μM. Apoptosis Analysis[1] Cell Types: U87 glioblastoma cells. Tested Concentrations: 16 μM. Incubation Duration: 12h, 24h and 48h. Experimental Results: Induced apoptosis. diminished caspase-3. 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] |
| Animal Protocol |
Animal/Disease Models: U87 cells were subcutaneously (sc) injected into the nude mice[1].
Doses: 16 mg/kg. Route of Administration: Once every 3 days for 12 days. Experimental Results: Dramatically diminished the tumor volumes. A significant decrease in Ki67 (a marker for proliferating cells that is overexpressed in many cancers) staining in sections of dapivirine-treated tumors compared to tumors from vehicle-treated mice. 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] |
| ADME/Pharmacokinetics |
Dapiridine (TMC120) is poorly 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 distribution volume in the vaginal mucosa (rhesus monkey Vd = 5.2 L/kg) [4] The content of metabolized dapiridine (TMC120) in vaginal tissues is extremely low, with more than 80% of the drug existing unchanged [2] |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Dapirvirin is still in the investigational stage in the United States, but it is used overseas as a vaginal ring for pre-exposure prophylaxis (PrEP) of HIV infection. This formulation can be used during lactation. ◉ Effects on Breastfed Infants One study compared the efficacy of dapirvirin vaginal rings with emtricitabine in combination with tenofovir in preventing HIV infection. In 148 mother-infant pairs receiving dapirvirin vaginal rings, no adverse reactions related to dapirvirin were observed in the infants. ◉ Effects on Lactation and Breast Milk As of the revision date, no relevant published information was found. Dapiril (TMC120) has low cytotoxicity to normal human astrocytes and vaginal epithelial cells, CC50 > 50 μM [1][2] Dapiril (TMC120) has a plasma protein binding rate of 99.5% in humans [4] Dapiril (TMC120)-loaded vaginal rings do not cause significant irritation or inflammation of the vaginal mucosa in mice and rhesus monkeys [2] In vitro studies have shown that Dapiril (TMC120) does not inhibit cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP3A4) at concentrations up to 10 μM [4] Dapiril (TMC120) has an intraperitoneal LD50 of > 50 mg/kg in mice [1] |
| References |
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| Additional Infomation |
Dapivirine is an investigational drug currently being studied as a topical antimicrobial agent to prevent the sexual transmission of HIV. Dapivirine belongs to the class of nonnucleoside reverse transcriptase inhibitors (NNRTIs) for HIV. NNRTIs can bind to an enzyme in HIV called reverse transcriptase 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 active against wild-type viral strains and viral strains carrying different NNRTI resistance-inducing mutations, and may have direct antiviral activity. Dapivirine (TMC120) is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) that was initially developed for HIV-1 prevention[2].
Dapiril (TMC120) exerts its anti-HIV activity by binding to the NNRTI binding pocket of HIV-1 reverse transcriptase, inducing conformational changes, thereby blocking viral DNA synthesis[3]. Dapiril (TMC120) has anti-tumor potential against glioblastoma by inhibiting cellular reverse transcriptase-like activity and inducing apoptosis in cancer cells[1]. Dapiril (TMC120) has been approved by the FDA as a vaginal ring (1% w/w) for pre-exposure prophylaxis. Pre-exposure prophylaxis (PrEP) for HIV-1 infection in women[2] The dapiril (TMC120) vaginal ring formulation is designed for monthly use, providing convenient and continuous HIV prevention[4] |
| Molecular Formula |
C20H19N5
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| Molecular Weight |
329.4
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| Exact Mass |
329.164
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| Elemental Analysis |
C, 72.92; H, 5.81; N, 21.26
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| CAS # |
244767-67-7
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| Related CAS # |
Dapivirine-d11;1329613-10-6; 244767-67-7; 244768-47-6 (HCl)
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| PubChem CID |
214347
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
557.9±60.0 °C at 760 mmHg
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| Flash Point |
291.2±32.9 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.649
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| LogP |
3.98
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
452
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=C(C(=C1)C)NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C
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| InChi Key |
ILAYIAGXTHKHNT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19N5/c1-13-10-14(2)19(15(3)11-13)24-18-8-9-22-20(25-18)23-17-6-4-16(12-21)5-7-17/h4-11H,1-3H3,(H2,22,23,24,25)
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| Chemical Name |
4-[[4-[(2,4,6-Trimethylphenyl)amino]-2-pyrimidinyl]amino]benzonitrile
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (6.31 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0358 mL | 15.1791 mL | 30.3582 mL | |
| 5 mM | 0.6072 mL | 3.0358 mL | 6.0716 mL | |
| 10 mM | 0.3036 mL | 1.5179 mL | 3.0358 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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