Dapivirine
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MedKoo CAT#: 317132

CAS#: 244767-67-7

Description: Dapivirine, also known as TMC120, is a non-nucleoside inhibitor for HIV reverse transcriptase with IC50 of 24 nM. The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising drug candidates being used in topical microbicide products for prevention of HIV-1 sexual transmission.

Chemical Structure

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Dapivirine
CAS# 244767-67-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 317132
Name: Dapivirine
CAS#: 244767-67-7
Chemical Formula: C20H19N5
Exact Mass: 329.16
Molecular Weight: 329.410
Elemental Analysis: C, 72.92; H, 5.81; N, 21.26

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 350 Ready to ship
200mg USD 450 Ready to ship
500mg USD 950 Ready to ship
1g USD 1650 Ready to ship
2g USD 2950 Ready to ship
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Synonym: TMC120; TMC 120; TMC-120; R 147681; R-147681; R147681; Dapivirine.

IUPAC/Chemical Name: 4-[[4-[(2,4,6-Trimethylphenyl)amino]-2-pyrimidinyl]amino]benzonitrile

InChi Key: ILAYIAGXTHKHNT-UHFFFAOYSA-N

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)

SMILES Code: N#CC1=CC=C(NC2=NC=CC(NC3=C(C)C=C(C)C=C3C)=N2)C=C1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Dapivirine (TMC120) is a nonnucleoside reverse transcriptase inhibitor (NRTI).
In vitro activity: It was found that dapivirine inhibited A/California/07/2009 (H1N1) replication in a dose-dependent manner with an EC50 of 1.2 ± 0.1 μM (Fig. 1D). The cytotoxicity of dapivirine in MDCK cells was 14.3 ± 0.3 μM with 48 h incubation time (same as plaque assay); therefore, the observed antiviral effect was not due to the cellular cytotoxicity of dapivirine. Dapivirine was also found to inhibit the B/Brisbane/60/2008 virus with EC50 value of 1.1 ± 0.1 μM in plaque assay (Fig. 1D). Reference: Antiviral Res. 2017 Sep; 145: 103–113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599177/
In vivo activity: The tumor volumes of dapivirine-treated cells were significantly decreased in mice than controls (Fig. 4D and 4E). These results indicate that cancer proliferation is inhibited by dapivirine in vivo. In addition, proliferation status of tumor tissues was evaluated by Ki67, a marker for proliferating cells that is over-expressed in many cancers. Immunohistochemistry experiments performed on the sections of U87 tumor tissues showed a significant decrease in Ki67 staining in sections of dapivirine-treated tumors compared to tumors from vehicle-treated mice (Fig. 5E-F). Specifically, quantification of Ki67 positive cells revealed that dapivirine treatment reduced tumor growth by 2.8-fold and reduced cell proliferation (Ki67) by 2.6-fold with in U87. Reference: J Cancer. 2018; 9(1): 117–128. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743718/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 27.1 82.18
DMF 0.3 0.91
DMF:PBS (pH 7.2) (1:3) 0.3 0.76

Preparing Stock Solutions

The following data is based on the product molecular weight 329.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Hu Y, Zhang J, Musharrafieh RG, Ma C, Hau R, Wang J. Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses. Antiviral Res. 2017 Sep;145:103-113. doi: 10.1016/j.antiviral.2017.07.016. Epub 2017 Aug 2. PMID: 28778830; PMCID: PMC5599177. 2. Fletcher P, Harman S, Azijn H, Armanasco N, Manlow P, Perumal D, de Bethune MP, Nuttall J, Romano J, Shattock R. Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2009 Feb;53(2):487-95. doi: 10.1128/AAC.01156-08. Epub 2008 Nov 24. PMID: 19029331; PMCID: PMC2630639. 3. Liu W, Song XL, Zhao SC, He M, Wang H, Chen Z, Xiang W, Yi G, Qi S, Liu Y. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer. 2018 Jan 1;9(1):117-128. doi: 10.7150/jca.21965. PMID: 29290776; PMCID: PMC5743718. 4. Shi L, Yu L, Zhong D, Gu C, Lv L, Zeng X, Yao X, Li L, Liu S. TMC120 displayed potent cytotoxic effect on human cervical carcinoma through enhancing the polymerization of microtubules. AIDS. 2018 Jun 1;32(9):1107-1114. doi: 10.1097/QAD.0000000000001808. PMID: 29596107.
In vitro protocol: 1. Hu Y, Zhang J, Musharrafieh RG, Ma C, Hau R, Wang J. Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses. Antiviral Res. 2017 Sep;145:103-113. doi: 10.1016/j.antiviral.2017.07.016. Epub 2017 Aug 2. PMID: 28778830; PMCID: PMC5599177. 2. Fletcher P, Harman S, Azijn H, Armanasco N, Manlow P, Perumal D, de Bethune MP, Nuttall J, Romano J, Shattock R. Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2009 Feb;53(2):487-95. doi: 10.1128/AAC.01156-08. Epub 2008 Nov 24. PMID: 19029331; PMCID: PMC2630639.
In vivo protocol: 1. Shi L, Yu L, Zhong D, Gu C, Lv L, Zeng X, Yao X, Li L, Liu S. TMC120 displayed potent cytotoxic effect on human cervical carcinoma through enhancing the polymerization of microtubules. AIDS. 2018 Jun 1;32(9):1107-1114. doi: 10.1097/QAD.0000000000001808. PMID: 29596107. 2. Liu W, Song XL, Zhao SC, He M, Wang H, Chen Z, Xiang W, Yi G, Qi S, Liu Y. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer. 2018 Jan 1;9(1):117-128. doi: 10.7150/jca.21965. PMID: 29290776; PMCID: PMC5743718.

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1: Dezzutti CS, Yandura S, Wang L, Moncla B, Teeple EA, Devlin B, Nuttall J, Brown ER, Rohan LC. Pharmacodynamic Activity of Dapivirine and Maraviroc Single Entity and Combination Topical Gels for HIV-1 Prevention. Pharm Res. 2015 Nov;32(11):3768-81. doi: 10.1007/s11095-015-1738-7. Epub 2015 Jun 16. PubMed PMID: 26078001.

2: Palanee-Phillips T, Schwartz K, Brown ER, Govender V, Mgodi N, Kiweewa FM, Nair G, Mhlanga F, Siva S, Bekker LG, Jeenarain N, Gaffoor Z, Martinson F, Makanani B, Naidoo S, Pather A, Phillip J, Husnik MJ, van der Straten A, Soto-Torres L, Baeten J. Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention. PLoS One. 2015 Jun 10;10(6):e0128857. doi: 10.1371/journal.pone.0128857. eCollection 2015. PubMed PMID: 26061040; PubMed Central PMCID: PMC4489588.

3: Chen BA, Panther L, Marzinke MA, Hendrix CW, Hoesley CJ, van der Straten A, Husnik MJ, Soto-Torres L, Nel A, Johnson S, Richardson-Harman N, Rabe LK, Dezzutti CS. Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics of Dapivirine and Maraviroc Vaginal Rings: a Double-Blind Randomized Trial. J Acquir Immune Defic Syndr. 2015 May 28. [Epub ahead of print] PubMed PMID: 26034880.

4: das Neves J, Sarmento B. Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides. Acta Biomater. 2015 May;18:77-87. doi: 10.1016/j.actbio.2015.02.007. Epub 2015 Feb 17. PubMed PMID: 25700657.

5: Grammen C, Plum J, Van Den Brande J, Darville N, Augustyns K, Augustijns P, Brouwers J. The use of supersaturation for the vaginal application of microbicides: a case study with dapivirine. J Pharm Sci. 2014 Nov;103(11):3696-703. doi: 10.1002/jps.24176. Epub 2014 Sep 17. PubMed PMID: 25231545.

6: Parsons TL, Emory JF, Seserko LA, Aung WS, Marzinke MA. Dual quantification of dapivirine and maraviroc in cervicovaginal secretions from ophthalmic tear strips and polyester-based swabs via liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analysis. J Pharm Biomed Anal. 2014 Sep;98:407-16. doi: 10.1016/j.jpba.2014.06.018. Epub 2014 Jun 21. PubMed PMID: 25005891; PubMed Central PMCID: PMC4143664.

7: Nel A, Haazen W, Nuttall J, Romano J, Rosenberg Z, van Niekerk N. A safety and pharmacokinetic trial assessing delivery of dapivirine from a vaginal ring in healthy women. AIDS. 2014 Jun 19;28(10):1479-87. doi: 10.1097/QAD.0000000000000280. PubMed PMID: 24901365.

8: Murphy DJ, Desjardins D, Dereuddre-Bosquet N, Brochard P, Perrot L, Pruvost A, Le Grand R, Lagatie O, Vanhooren L, Feyaerts M, van Roey J, Malcolm RK. Pre-clinical development of a combination microbicide vaginal ring containing dapivirine and darunavir. J Antimicrob Chemother. 2014 Sep;69(9):2477-88. doi: 10.1093/jac/dku160. Epub 2014 May 26. PubMed PMID: 24862093.

9: Akil A, Devlin B, Cost M, Rohan LC. Increased Dapivirine tissue accumulation through vaginal film codelivery of dapivirine and Tenofovir. Mol Pharm. 2014 May 5;11(5):1533-41. doi: 10.1021/mp4007024. Epub 2014 Apr 14. PubMed PMID: 24693866; PubMed Central PMCID: PMC4018102.

10: das Neves J, Araújo F, Andrade F, Amiji M, Bahia MF, Sarmento B. Biodistribution and pharmacokinetics of dapivirine-loaded nanoparticles after vaginal delivery in mice. Pharm Res. 2014 Jul;31(7):1834-45. doi: 10.1007/s11095-013-1287-x. Epub 2014 Jan 22. PubMed PMID: 24449442.

11: Seserko LA, Emory JF, Hendrix CW, Marzinke MA. The development and validation of an UHPLC-MS/MS method for the rapid quantification of the antiretroviral agent dapivirine in human plasma. Bioanalysis. 2013 Nov;5(22):2771-83. doi: 10.4155/bio.13.256. PubMed PMID: 24256358; PubMed Central PMCID: PMC4104354.

12: Devlin B, Nuttall J, Wilder S, Woodsong C, Rosenberg Z. Development of dapivirine vaginal ring for HIV prevention. Antiviral Res. 2013 Dec;100 Suppl:S3-8. doi: 10.1016/j.antiviral.2013.09.025. Epub 2013 Nov 1. Review. PubMed PMID: 24188702.

13: Cranston RD, Hoesley C, Carballo-Diéguez A, Hendrix CW, Husnik M, Levy L, Hall W, Soto-Torres L, Nel AM. A randomized male tolerance study of dapivirine gel following multiple topical penile exposures (MTN 012/IPM 010). AIDS Res Hum Retroviruses. 2014 Feb;30(2):184-9. doi: 10.1089/AID.2013.0170. Epub 2013 Oct 26. PubMed PMID: 24070431; PubMed Central PMCID: PMC3910451.

14: das Neves J, Amiji M, Bahia MF, Sarmento B. Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles. Int J Pharm. 2013 Nov 18;456(2):307-14. doi: 10.1016/j.ijpharm.2013.08.049. Epub 2013 Sep 4. PubMed PMID: 24012910.

15: das Neves J, Araújo F, Andrade F, Michiels J, Ariën KK, Vanham G, Amiji M, Bahia MF, Sarmento B. In vitro and ex vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine. Mol Pharm. 2013 Jul 1;10(7):2793-807. doi: 10.1021/mp4002365. Epub 2013 Jun 17. PubMed PMID: 23738946.

16: Gorajana A, Ying CC, Shuang Y, Fong P, Tan Z, Gupta J, Talekar M, Sharma M, Garg S. Development of solid dispersion systems of dapivirine to enhance its solubility. Curr Drug Deliv. 2013 Jun;10(3):309-16. PubMed PMID: 23360246.

17: das Neves J, Sarmento B, Amiji M, Bahia MF. Development and validation of a HPLC method for the assay of dapivirine in cell-based and tissue permeability experiments. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Dec 12;911:76-83. doi: 10.1016/j.jchromb.2012.10.034. Epub 2012 Nov 2. PubMed PMID: 23217310.

18: Major I, Boyd P, Kilbourne-Brook M, Saxon G, Cohen J, Malcolm RK. A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine. Contraception. 2013 Jul;88(1):58-66. doi: 10.1016/j.contraception.2012.10.018. Epub 2012 Nov 21. PubMed PMID: 23177261.

19: Akil A, Parniak MA, Dezzuitti CS, Moncla BJ, Cost MR, Li M, Rohan LC. Development and Characterization of a Vaginal Film Containing Dapivirine, a Non- nucleoside Reverse Transcriptase Inhibitor (NNRTI), for prevention of HIV-1 sexual transmission. Drug Deliv Transl Res. 2011 Jun 1;1(3):209-222. PubMed PMID: 22708075; PubMed Central PMCID: PMC3375737.

20: Schader SM, Oliveira M, Ibanescu RI, Moisi D, Colby-Germinario SP, Wainberg MA. In vitro resistance profile of the candidate HIV-1 microbicide drug dapivirine. Antimicrob Agents Chemother. 2012 Feb;56(2):751-6. doi: 10.1128/AAC.05821-11. Epub 2011 Nov 28. PubMed PMID: 22123692; PubMed Central PMCID: PMC3264246.