Comprehensive Report on the Investigational Compound DB01721: An Indinavir Analogue Targeting HIV-1 Protease

I. Introduction and Compound Identification

A. Overview of DB01721 as an Experimental Small Molecule Drug Candidate

The compound identified by DrugBank accession number DB01721 is an experimental small molecule that has garnered attention primarily for its structural relationship to Indinavir, an established Human Immunodeficiency Virus (HIV) protease inhibitor.[1] As an analogue of Indinavir, DB01721 has been a subject of research aimed at understanding and potentially overcoming the pervasive challenge of drug resistance in HIV-1 therapy. Its investigation is highlighted by detailed structural and biochemical analyses, particularly its interaction with multi-drug resistant (MDR) variants of the HIV-1 protease enzyme.[2]

The study of DB01721 is emblematic of a critical strategy in antiviral drug development: the modification of existing, clinically successful drugs to address limitations such as emergent viral resistance or suboptimal pharmacological profiles. Indinavir, while a potent therapeutic, has seen its utility diminished by the selection of resistant HIV-1 strains and a demanding clinical regimen.[5] The development of analogues like DB01721, which incorporates specific dual modifications to the Indinavir scaffold, represents a rational medicinal chemistry approach. The evaluation of such analogues against MDR HIV-1 protease aims not only to identify new therapeutic candidates but also to deepen the understanding of structure-activity relationships (SAR) and the molecular mechanisms by which resistance can be circumvented. The detailed characterization of DB01721, particularly the finding that its combined modifications did not lead to improved potency against a resistant protease [3], provides valuable insights into the complexities of inhibitor design and the adaptive capabilities of viral targets. This iterative process of