| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| 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 |
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.
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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 |
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| Additional Infomation |
Dapirine hydrochloride is an investigational drug being studied as a topical antimicrobial agent for the prevention of sexually transmitted HIV infection. Dapirine belongs to the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. NNRTIs bind to and block the activity of reverse transcriptase, an enzyme in HIV. Dapirine has been investigated for the prevention of HIV-1 infection and penile exposure. Dapirine is a diarylpyrimidine NNRTI inhibitor. It is effective against wild-type HIV strains and strains carrying various NNRTI resistance mutations, and may possess direct antiviral activity.
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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 # |
1329613-10-6; 244767-67-7; 244768-47-6 (HCl)
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| PubChem CID |
22398432
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
452
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| Defined Atom Stereocenter Count |
0
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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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| InChi Key |
RHIYZDNOTUMYCA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19N5.ClH/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);1H
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| Chemical Name |
4-[[4-(2,4,6-trimethylanilino)pyrimidin-2-yl]amino]benzonitrile;hydrochloride
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| Synonyms |
Dapivirine hydrochloride; 244768-47-6; UNII-55D48BY90H; 55D48BY90H; Benzonitrile, 4-((4-((2,4,6-trimethylphenyl)amino)-2-pyrimidinyl)amino)-, hydrochloride (1:1);
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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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