Abstract
At Bristol-Myers (BM) (1985–1990), John C. Martin started his HIV career with directing the clinical development of didanosine (ddI) and stavudine (d4T). During this period, he became aware of the acyclic nucleoside phosphonates (ANPs), such as (S)-HPMPA and PMEA, as potential antiviral drugs. Under his impulse, BM got involved in the evaluation of these ANPs, but the merger of BM with Squibb (to become BMS) incited John to leave BM and join Gilead Sciences, and the portfolio of the ANPs followed the transition. At Gilead, John succeeded in obtaining the approval from the US FDA for the use of cidofovir in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients, which was reminiscent of John’s first experience with ganciclovir (at Syntex) as an anti-CMV agent. At Gilead, John would then engineer the development of tenofovir, first as TDF (tenofovir disoproxil fumarate) and then as TAF (tenofovir alafenamide) and various combinations thereof, for the treatment of HIV infections (i), TDF and TAF for the treatment of hepatitis B (HBV) infections (ii), and TDF and TAF in combination with emtricitabine for the prophylaxis of HIV infections (iii).
Highlights
Introduction to the Antiviral Drug FieldGanciclovirJohn C
At Gilead, John would engineer the development of tenofovir, first as Tenofovir disoproxil fumarate (TDF) and as Tenofovir alafenamide (TAF) and various combinations thereof, for the treatment of human immunodeficiency virus (HIV) infections (i), TDF and TAF for the treatment of hepatitis B (HBV) infections (ii), and TDF and TAF in combination with emtricitabine for the prophylaxis of HIV infections (iii)
Ganciclovir would later be derivatized to its aminoacyl ester, valganciclovir, in analogy with acyclovir that was converted to valacyclovir, its valine ester, to ensure improved oral bioavailability
Summary
On 26 October 2001, 20 years ago, tenofovir in its prodrug form, TDF (tenofovir disoproxil fumarate), was formally approved by the US FDA (Food and Drug Administration) for the treatment of HIV infections. Officer (1995–2020) of Gilead Sciences, intended to commemorate the 20th anniversary of this milestone event in the fight against AIDS (HIV infection), but John suddenly died on. 30 March 2021, a few weeks before his 70th birthday. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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