This paper might be of interest to the BIT investors [1] as it is an independent (if biased) assessment of BIT225. Two things were very interesting.
1. BIT225 is thought to be too toxic to use. Quoting from the paper
Two acylguanidine-containing compounds, HMA (Fig. 1A) and BIT-225 (Fig. 1B), are reported to inhibit HIV-1 replication; however, both display substantial in vitro toxicity, particularly to T cells (5, 6, 34, 35). We therefore sought to design an acylguanidine-based derivative with a reduced cytotoxic component. We observed that the heterocyclic amino-pyrazine core of HMA resembles the heterocyclic core of methotrexate, which is also cytotoxic (46), and speculated that the high nitrogen density in these cores might be a cause.
2. HIV-1 resistance mutations to acylguanidines can be easily be isolated. The highly conserved structure of VPU does not seem to prevent HIV-1 resistance mutations arising in this protein.
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044834/
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