Didanosine-d2 (Synonyms: ddl-d2, 2′,3′-Dideoxyinosine-d2)

Didanosine-d₂ is intended for use as an internal standard for the quantification of didanosine by GC- or LC-MS. Didanosine is an antiviral nucleoside analog and an inhibitor of reverse transcriptase.¹ It undergoes cellular amination and phosphorylation to its active triphosphate form, 2’,3’-dideoxyadenosine 5’-triphosphate . Didanosine inhibits human T cell leukemia virus type 1 (HTLV-1) reverse transcriptase activity (IC₅₀ = 30 nM).² It inhibits the replication of HIV-1 clinical isolates containing various mutations in the gene encoding reverse transcriptase, pol, in isolated human peripheral blood mononuclear cells (PBMCs; IC₅₀s = 0.3-11.1 μM).³ Didanosine inhibits proliferation and differentiation of primary human skeletal muscle cells (IC₅₀s = 1 and 0.1 mM, respectively), as well as decreases the activities of mitochondrial complex IV, also known as cytochrome c oxidase, and mitochondrial complex II, also known as succinate dehydrogenase, in the same cells when used at a concentration of 1 mM.⁴ In vivo, didanosine protects mice from HIV infection (EC₅₀ = 13.7 mg/kg).⁵ Formulations containing didanosine have been used in the treatment of HIV-1 infections.

1.Perry, C.M., and Noble, S.Didanosine: An updated review of its use in HIV infectionDrugs58(6)1099-1135(1999) 2.Anantharaman, V., and Moen, L.K.Effects of nucleoside analogs on native and site-directed mutants of HTLV type 1 reverse transcriptaseBioorg. Chem.28(5)293-305(2000) 3.Eron, J.J., Chow, Y.-K., Caliendo, A.M., et al.pol Mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivoAntimicrob. Agents Chemother.37(7)1480-1487(1993) 4.Benbrik, E., Chariot, P., Bonavaud, S., et al.Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cellsJ. Neurol. Sci.149(1)19-25(1997) 5.Kaneshima, H., Shih, C.C., Namikawa, R., et al.Human immunodeficiency virus infection of human lymph nodes in the SCID-hu mouseProc. Natl. Acad. Sci. USA88(10)4523-4527(1991)