WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H315142
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.
Hodoodo Cat#: H315142
Name: Dolutegravir
CAS#: 1051375-16-6 (free)
Chemical Formula: C20H19F2N3O5
Exact Mass: 419.13
Molecular Weight: 419.380
Elemental Analysis: C, 57.28; H, 4.57; F, 9.06; N, 10.02; O, 19.08
Related CAS #: 1051375-19-9 (sodium) 1051375-16-6 (free)
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
More Info: 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.
| 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 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 | |
|---|---|---|---|
| Solubility | |||
| DMSO | 31.8 | 75.90 | |
| DMF | 5.0 | 11.92 | |
| 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: Scott LJ. Dolutegravir/Lamivudine Single-Tablet Regimen: A Review in HIV-1 Infection. Drugs. 2020 Jan;80(1):61-72. doi: 10.1007/s40265-019-01247-1. PMID: 31865558.
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5: Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, Asienzo J, Kaimal A, Mirembe G, Lugemwa A, Ategeka G, Borok M, Mugerwa H, Siika A, Odongpiny ELA, Castelnuovo B, Kiragga A, Kambugu A; NADIA Trial Team. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. Lancet HIV. 2022 Jun;9(6):e381-e393. doi: 10.1016/S2352-3018(22)00092-3. Epub 2022 Apr 20. PMID: 35460601.
6: Turkova A, Waalewijn H, Chan MK, Bollen PDJ, Bwakura-Dangarembizi MF, Kekitiinwa AR, Cotton MF, Lugemwa A, Variava E, Ahimbisibwe GM, Srirompotong U, Mumbiro V, Amuge P, Zuidewind P, Ali S, Kityo CM, Archary M, Ferrand RA, Violari A, Gibb DM, Burger DM, Ford D, Colbers A; ODYSSEY Trial Team. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e627-e637. doi: 10.1016/S2352-3018(22)00160-6. Epub 2022 Jul 19. PMID: 35868341; PMCID: PMC9630157.
7: Blair HA. Dolutegravir/Rilpivirine: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(16):1741-1750. doi: 10.1007/s40265-018-1005-4. PMID: 30406902.
8: Ciccullo A, Baldin G, Borghetti A, Di Giambenedetto S. Dolutegravir plus lamivudine for the treatment of HIV-1 infection. Expert Rev Anti Infect Ther. 2020 Apr;18(4):279-292. doi: 10.1080/14787210.2020.1729742. Epub 2020 Feb 18. PMID: 32067525.
9: Orkin C, DeJesus E, Sax PE, Arribas JR, Gupta SK, Martorell C, Stephens JL, Stellbrink HJ, Wohl D, Maggiolo F, Thompson MA, Podzamczer D, Hagins D, Flamm JA, Brinson C, Clarke A, Huang H, Acosta R, Brainard DM, Collins SE, Martin H; GS-US-380-1489; GS-US-380-1490 study investigators. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir- containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020 Jun;7(6):e389-e400. doi: 10.1016/S2352-3018(20)30099-0. PMID: 32504574.
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11: Venter WDF, Sokhela S, Simmons B, Moorhouse M, Fairlie L, Mashabane N, Serenata C, Akpomiemie G, Masenya M, Qavi A, Chandiwana N, McCann K, Norris S, Chersich M, Maartens G, Lalla-Edward S, Vos A, Clayden P, Abrams E, Arulappan N, Hill A. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV. 2020 Oct;7(10):e666-e676. doi: 10.1016/S2352-3018(20)30241-1. PMID: 33010240.
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13: Christensen BL, Tan DH. An up-to-date evaluation of dolutegravir/abacavir/lamivudine for the treatment of HIV. Expert Opin Pharmacother. 2022 Mar;23(4):439-446. doi: 10.1080/14656566.2022.2029409. Epub 2022 Jan 24. PMID: 35073817.
14: Dolutegravir/lamivudine (Dovato)--a two-drug complete regimen for HIV-1 infection. Med Lett Drugs Ther. 2019 Aug 26;61(1579):134-136. PMID: 31581158.
15: Wu G, Abraham T, Saad N. Dolutegravir for the treatment of adult patients with HIV-1 infection. Expert Rev Anti Infect Ther. 2014 May;12(5):535-44. doi: 10.1586/14787210.2014.907525. Epub 2014 Apr 2. PMID: 24694091.
16: Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar ES, Wohl D, Rockstroh J, Wei X, Custodio J, White K, Martin H, Cheng A, Quirk E. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2063-2072. doi: 10.1016/S0140-6736(17)32299-7. Epub 2017 Aug 31. PMID: 28867497.
17: Wainberg MA, Han YS, Mesplède T. Might dolutegravir be part of a functional cure for HIV? Can J Microbiol. 2016 May;62(5):375-82. doi: 10.1139/cjm-2015-0725. Epub 2016 Jan 27. PMID: 27031127.
18: Blanco JL, Marcelin AG, Katlama C, Martinez E. Dolutegravir resistance mutations: lessons from monotherapy studies. Curr Opin Infect Dis. 2018 Jun;31(3):237-245. doi: 10.1097/QCO.0000000000000453. PMID: 29634660.
19: Hester EK, Astle K. Dolutegravir-Rilpivirine, Dual Antiretroviral Therapy for the Treatment of HIV-1 Infection. Ann Pharmacother. 2019 Aug;53(8):860-866. doi: 10.1177/1060028019831674. Epub 2019 Feb 13. PMID: 30758229.
20: The Lancet Hiv. End resistance to dolutegravir roll-out. Lancet HIV. 2020 Sep;7(9):e593. doi: 10.1016/S2352-3018(20)30231-9. PMID: 32890495
