Dapivirine (TMC120)

製品コードS2914 バッチS291401

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H19N5
分子量 329.4 CAS No. 244767-67-7
Solubility (25°C)* 体外 DMSO 34 mg/mL (103.21 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 1.700mg/ml (5.16mM) Taking the 1 mL working solution as an example, add 50 μL of 34 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution
5% DMSO 95% Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 0.240mg/ml (0.73mM) Taking the 1 mL working solution as an example, add 50 μL of 4.8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Dapivirine (TMC120) is a non-nucleoside inhibitor for HIV reverse transcriptase with IC50 of 24 nM, inhibits a broad panel of HIV-1 isolates from different classes, inclucing a wide range of NNRTI-resistant isolates. Phase 3.
in vitro Dapivirine (TMC120) prevents HIV-induced syncytium formation in the nanomolar range and shows a low cytostatic activity. It 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. [1] This compound is well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants with CC50 (50% cytotoxic concentration) of 10 μM to 20 μM. It potently inhibits infection by both X4- and R5-utilizing HIV-1 strains with IC50 of 1.46 nM in cell-based assays. It also potently inhibits HIV-1BaL infection of human ectocervical explant tissue in a dose-dependent manner, as evaluated by the reduction in both p24 release and provirus content in cultured explants. It inhibits the transmission of virus to permissive T cells in a dose-dependent manner, with an IC50 of 0.1 nM. It results in significant inhibition of HIV infection when explants are challenged with virus immediately with IC90 of 100 nM. It is also able to inhibit viral dissemination by migratory cells. [2]
in vivo Dapivirine (TMC120)-containing gel at vaginal level inhibits cell-associated HIV infection in mice. [3] More placebo (7 of 12) than this compound (3 of 24) gel users has positive vaginal swab results, with white blood cells being the most common finding. It results in Cmax of 715 pg/mL, AUC of 15 ng×h/mL and T1/2 of 89.87 hours in plasma after 14 days post-dose. Mean concentrations of the compound in vaginal fluids collected at the introitus, mid vagina, and cervix are in the range of 62-265 μg/g on day 1. [4]

プロトコル(参考用のみ)

参考

  • https://pubmed.ncbi.nlm.nih.gov/14693562/
  • https://pubmed.ncbi.nlm.nih.gov/19029331/
  • https://pubmed.ncbi.nlm.nih.gov/12853741/
  • https://pubmed.ncbi.nlm.nih.gov/20574411/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Next-generation 3D printed multipurpose prevention intravaginal ring for prevention of HIV, HSV-2, and unintended pregnancy [ J Control Release, 2024, 376:1209-1224] PubMed: 39500407
Multifaceted impact of HIV inhibitor dapivirine on triple negative breast cancer cells reveals potential entities as targets for novel therapy [ Sci Rep, 2024, 14(1):30103] PubMed: 39627279
Comprehensive Study of Antiretroviral Drug Permeability at the Cervicovaginal Mucosa via an In Vitro Model [ Pharmaceutics, 2022, 14(9)1938] PubMed: 36145684
Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV [ Viruses, 2022, 14(8)1723] PubMed: 36016345
Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism [ PLoS Pathog, 2020, 16(12):e1009024] PubMed: 33270801
Reciprocal Modulation of Antiretroviral Drug and Steroid Receptor Function In Vitro. [ Antimicrob Agents Chemother, 2019, 64(1)] PubMed: 31658973
Combination of G2-S16 dendrimer/dapivirine antiretroviral as a new HIV-1 microbicide. [ Future Med Chem, 2019, 11(23):3005-3013] PubMed: 31710246
Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. [ J Cancer, 2018, 9(1):117-128] PubMed: 29290776
In Silico and in Vitro Screening for P-Glycoprotein Interaction with Tenofovir, Darunavir, and Dapivirine: An Antiretroviral Drug Combination for Topical Prevention of Colorectal HIV Transmission. [ Mol Pharm, 2017, 14(8):2660-2669] PubMed: 28648081
In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150, Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical Development for the Prevention of HIV-1 Infection. [ Antimicrob Agents Chemother, 2017, 61(7)] PubMed: 28507107

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。