WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 315142
CAS#: 1051375-16-6 (free)
Description: Dolutegravir, also known as GSK1349572, is a potent inhibitor of HIV integrase with an IC50 value of 2.7 nM for HIV-1 integrase-catalyzed strand transfer in vitro.1 It inhibits HIV-1 viral replication (EC50 = 0.51 nM) in peripheral blood mononuclear cells (PBMCs). Dolutegravir (DTG) is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential exposure.
MedKoo Cat#: 315142
CAS#: 1051375-16-6 (free)
Chemical Formula: C20H19F2N3O5
Exact Mass: 419.12928
Molecular Weight: 419.38
Elemental Analysis: C, 57.28; H, 4.57; F, 9.06; N, 10.02; O, 19.08
Synonym: Dolutegravir; GSK1349572; GSK-1349572; GSK 1349572; Tivicay; S/GSK1349572.
IUPAC/Chemical Name: (4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide
InChi Key: RHWKPHLQXYSBKR-BMIGLBTASA-N
InChi Code: InChI=1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1
SMILES Code: O=C(C1=CN(C2=C(O)C1=O)C[C@]3([H])OCC[C@@H](C)N3C2=O)NCC4=CC=C(F)C=C4F
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.
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
|Biological target:||Dolutegravir is a potent inhibitor of HIV integrase with an IC50 of 2.7 nM for HIV-1 integrase-catalyzed strand transfer.|
|In vitro activity:||To evaluate the potential role of dolutegravir in HIV-2 treatment, the susceptibilities of wild-type and INSTI-resistant HIV-1 and HIV-2 strains to dolutegravir were compared using single-cycle assays, spreading infections of immortalized T cells, and site-directed mutagenesis. HIV-2 group A, HIV-2 group B, and HIV-1 isolates from INSTI-naïve individuals were comparably sensitive to dolutegravir in the single-cycle assay (mean EC50 values = 1.9, 2.6, and 1.3 nM, respectively). Integrase substitutions E92Q, Y143C, E92Q + Y143C, and Q148R conferred relatively low levels of resistance to dolutegravir in HIV-2ROD9 (2- to 6-fold), but Q148K, E92Q + N155H, T97A + N155H and G140S + Q148R resulted in moderate resistance (10- to 46-fold), and the combination of T97A + Y143C in HIV-2ROD9 conferred high-level resistance (>5000-fold). In contrast, HIV-1NL4-3 mutants E92Q + N155H, G140S + Q148R, and T97A + Y143C showed 2-fold, 4-fold, and no increase in EC50, respectively, relative to the parental strain. The resistance phenotypes for E92Q + N155H, and G140S + Q148R HIV-2ROD9 were also confirmed in spreading infections of CEM-ss cells. Reference: Retrovirology. 2015 Feb 5;12:10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4328052/|
|In vivo activity:||The efficacy of 20 week monotherapy with dolutegravir was evaluated in humanized mice (HSC-NSG) infected with HIVBaL. Drug-untreated control mice maintained constant viraemia throughout the study. Virus isolates from these mice were susceptible to dolutegravir (EC50 of <1 nM). Mice treated with dolutegravir had plasma drug levels comparable to those in humans. Monotherapy with dolutegravir suppressed viraemia in 5/5 of mice, but viraemia rebounded in one animal. The virus from this mouse had mutations E138K, G140S, Q148H, N155H and S230R, was highly resistant to both raltegravir (EC50 of >1000 nM) and dolutegravir (EC50 of 550 nM), and replicated to levels similar to those of control viruses in PBMCs. These results suggest that monotherapy with dolutegravir does not consistently maintain HIV suppression and that dual therapy may be required in simplification strategies. Reference: J Antimicrob Chemother. 2017 Sep 1;72(9):2570-2573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890682/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|DMF:PBS (pH 7.2) (1:4)||0.2||0.48|
The following data is based on the product molecular weight 419.38 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.
|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. Smith RA, Raugi DN, Pan C, Sow PS, Seydi M, Mullins JI, Gottlieb GS; University of Washington-Dakar HIV-2 Study Group. In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Retrovirology. 2015 Feb 5;12:10. doi: 10.1186/s12977-015-0146-8. PMID: 25808007; PMCID: PMC4328052. 2. Heredia A, Hassounah S, Medina-Moreno S, Zapata JC, Le NM, Han Y, Foulke JS Jr, Davis C, Bryant J, Redfield RR, Wainberg MA. Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice. J Antimicrob Chemother. 2017 Sep 1;72(9):2570-2573. doi: 10.1093/jac/dkx195. PMID: 28637235; PMCID: PMC5890682.|
|In vitro protocol:||1. Smith RA, Raugi DN, Pan C, Sow PS, Seydi M, Mullins JI, Gottlieb GS; University of Washington-Dakar HIV-2 Study Group. In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Retrovirology. 2015 Feb 5;12:10. doi: 10.1186/s12977-015-0146-8. PMID: 25808007; PMCID: PMC4328052.|
|In vivo protocol:||1. Heredia A, Hassounah S, Medina-Moreno S, Zapata JC, Le NM, Han Y, Foulke JS Jr, Davis C, Bryant J, Redfield RR, Wainberg MA. Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice. J Antimicrob Chemother. 2017 Sep 1;72(9):2570-2573. doi: 10.1093/jac/dkx195. PMID: 28637235; PMCID: PMC5890682.|
1: Llibre JM, Clotet B. Once-daily single-tablet regimens: a long and winding road to excellence in antiretroviral treatment. AIDS Rev. 2012 Jul;14(3):168-78. PubMed PMID: 22833060.
2: Rhodes MC, Laffan S, Genell C, Gower J, Maier C, Fukushima T, Nichols G, Eaton Bassiri A. Assessing a Theoretical Risk of Dolutegravir-Induced Developmental Immunotoxicity in Juvenile Rats. Toxicol Sci. 2012 Jul 12. [Epub ahead of print] PubMed PMID: 22790968.
3: Adams JL, Greener BN, Kashuba AD. Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012 Jul 19. [Epub ahead of print] PubMed PMID: 22789987.
4: Lennox JL. The use of HIV-1 integrase inhibitors in antiretroviral naive patients. Curr Opin HIV AIDS. 2012 Jul 19. [Epub ahead of print] PubMed PMID: 22789985.
5: Shamroe CL, Bookstaver PB, Rokas KE, Weissman SB. Update on raltegravir and the development of new integrase strand transfer inhibitors. South Med J. 2012 Jul;105(7):370-8. PubMed PMID: 22766666.
6: Saladini F, Meini G, Bianco C, Monno L, Punzi G, Pecorari M, Borghi V, Di Pietro M, Filice G, Gismondo MR, Micheli V, Penco G, Carli T, De Luca A, Zazzi M; for the ARCA Collaborative Group. Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naÃ¯ve and pretreated patients. Clin Microbiol Infect. 2012 May 28. doi: 10.1111/j.1469-0691.2012.03917.x. [Epub ahead of print] PubMed PMID: 22716970.
7: Quashie PK, Sloan RD, Wainberg MA. Novel therapeutic strategies targeting HIV integrase. BMC Med. 2012 Apr 12;10:34. Review. PubMed PMID: 22498430; PubMed Central PMCID: PMC3348091.
8: Nguyen HL, Ruxrungtham K, Delaugerre C. Genetic barrier to the development of resistance to integrase inhibitors in HIV-1 subtypes CRF01_AE and B. Intervirology. 2012;55(4):287-95. Epub 2012 Mar 23. PubMed PMID: 22456540.
9: Chen S, Min SS, Peppercorn A, Borland J, Lou Y, Song I, Fujiwara T, Piscitelli SC. Effect of a single supratherapeutic dose of dolutegravir on cardiac repolarization. Pharmacotherapy. 2012 Apr;32(4):333-9. doi: 10.1002/j.1875-9114.2012.01033.x. Epub 2012 Mar 15. PubMed PMID: 22422361.
10: Katlama C, Murphy R. Dolutegravir for the treatment of HIV. Expert Opin Investig Drugs. 2012 Apr;21(4):523-30. Epub 2012 Mar 2. Review. PubMed PMID: 22380682.
Dolutegravir, also known as GSK1349572, is an FDA-approved drug for the treatment of HIV infection. It can be used to treat HIV-infected adults who have never taken HIV therapy (treatment-naïve) and HIV-infected adults who have previously taken HIV therapy (treatment-experienced), including those who have been treated with other integrase strand transfer inhibitors. Tivicay is also approved for children ages 12 years and older weighing at least 40 kilograms (kg) who are treatment-naïve or treatment-experienced but have not previously taken other integrase strand transfer inhibitors.