Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: A brief history of stavudine (D4T) and its comparison with other dideoxynucleosides

Martin, John; Hitchcock, Michael; Clercq, Erik De; Prusoff, William H.

doi:10.1016/j.antiviral.2009.10.006

Cited by 51 publications

(43 citation statements)

References 58 publications

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“…Success came quickly with the (almost simultaneous) description of the anti-HIV activity of 2 ,3 -didehydro-2 ,3 -dideoxythymidine (stavudine, or d4T) by three groups [our own group in Leuven (55), Prusoff 's at Yale (56), and Yamamoto's in Tokyo (57)]. Stavudine would become the fourth and one of the most popular anti-HIV drugs to be used worldwide (58). Then these followed, in chronological order of their approval: the fifth, lamivudine [originally described as its racemic mixture BCH-189 (59) Acyclic guanosine analogs and their prodrugs.…”

Section: The 2 3 -Dideoxynucleoside Analogsmentioning

confidence: 99%

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

Clercq

2011

Annu. Rev. Pharmacol. Toxicol.

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My search for a selective antiviral chemotherapy started more than 40 years ago with interferon inducers, then shifted to nucleoside analogs with the discovery of BVDU (brivudin), a highly selective anti-HSV-1 and anti-VZV agent, and to dideoxynucleoside analogs such as d4T (stavudine), anti-HIV agents. The search culminated in the discovery of acyclic nucleoside phosphonates (ANPs) (in collaboration with Antonin Holý), a key class of compounds active against HIV, hepatitis B virus, and DNA viruses at large; the best known of these compounds is tenofovir. Along the way, the principle of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was established. This work, initiated in collaboration with the late Paul A.J. Janssen, eventually led to the identification of rilpivirine as perhaps an "ideal" NNRTI.1

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Section: The 2 3 -Dideoxynucleoside Analogsmentioning

confidence: 99%

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

Clercq

2011

Annu. Rev. Pharmacol. Toxicol.

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148

144

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“…Monotherapy is avoided as well because treatment with only competitive inhibitors slowed the progression of AIDS, but the drug resistance arose quickly Martin et al, 2010). Besides the viral resistance issue, these drugs cause different side effects (Table 1) that become extremely toxic in long term use (Temesgen et al, 2006;Sweeney & Klumpp, 2008;Cihlar & Ray, 2010).…”

Section: Hiv-1 Reverse Transcriptase (Hiv-1 Rt) -Still An Effective Tmentioning

confidence: 99%

“…This is analogous to the complexity of marine natural products, with a great variety of structures with different degrees of biological activity (De Clercq, 1998). NNRTI have in common the affi nity for the extremely fl exible hydrophobic p66 chain located near the active site (approximately 10 Å away) and located between the β-sheet-6-9-β-β and β-10-12-13-β-β-14 from the palm domain, called the "non-nucleoside inhibitor binding pocket" (NNIBP) (Boyer et al, 1994a(Boyer et al, , 1994bSluis-Cremer et al, 2004;Martin et al, 2010;Zhan et al, 2011). The inhibition mechanism is due to the expansion of the region of NNBIP, since this hydrophobic "pocket" is closed during the active period of TR.…”

Section: Terpenes As Nnrti Models: Looking At Future Anti-hiv Treatmementioning

confidence: 99%

HIV-1 Reverse Transcriptase: a potential target for marine products

Miceli¹,

Souza²,

Rodrigues³

et al. 2012

Rev. bras. farmacogn.

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HIV-1 reverse transcriptase (HIV-1 RT) is a therapeutic target for the treatment of HIV-positive individuals or those already showing AIDS symptoms. In this perspective, the identifi cation of new inhibitors for this enzyme is of great importance in view of the growing viral resistance to the existing treatments. This resistance has compromised the quality of life of those infected with multidrug-resistant strains, whose treatment options are already limited, putting at risk these individuals lives. The literature has recognized marine organisms and their products as natural sources for the identifi cation of new therapeutic options for different pathologies. In this brief review, we consider the structure of HIV-1 RT and its most common inhibitors, as well as some marine diterpenes originally reported as HIV-1 RT inhibitors to encourage the identifi cation and development of new marine antiviral prototypes.

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“…He serves as Senior Research Career Scientist at the Atlanta Department of Veterans Affairs and Director of the Scientific Working Group on Viral Eradication within the NIH-sponsored Emory University Center for AIDS Research (CFAR). He is probably best known for contributions to discovery and development of nucleoside anti-virals, for example: d4T (stavudine) [33], 3TC (lamivudine) [34,35], FTC (emtriva) [36,37], RCV (racivir) [38] and DAPD (amdoxovir) [39], drugs that are approved or in clinical development. Ray and co-workers have submitted a paper describing synthesis of novel 2′,3′-dideoxy-2′,3′-difluoro-D-arabino nucleosides and their HIV and HCV activities.…”

mentioning

confidence: 99%

Dedication to Kyoichi A. Watanabe

Patterson

2015

Heterocyclic Communications

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Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: A brief history of stavudine (D4T) and its comparison with other dideoxynucleosides

Cited by 51 publications

References 58 publications

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

HIV-1 Reverse Transcriptase: a potential target for marine products

Dedication to Kyoichi A. Watanabe

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