Joining the dark side: waterfall spiders in subterranean habitats, with the description of a new genus and two new species from Brazil (Araneae: Trechaleidae)

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  Joining the dark side: waterfall spiders in subterranean habitats, with the description of a new genus and two new species from Brazil (Araneae: Trechaleidae) Abstract Trechaleidae is a family of spiders often recognized by its semiaquatic species, but its diversity extends beyond these well-known examples. In this study, we describe Troglotrechalea gen. nov. , a new genus with two novel species, T. faleroae spec. nov. and T. agorai spec. nov. , found exclusively in subterranean habitats within karst formations in central and southeastern Brazil. Both species exhibit pale coloration, but unmodified eyes and legs if compared to other species in the family. The slight degree of troglomorphism, along with their geographic and habitat records, suggests that these species are restricted to hypogean habitats, although they probably move through epigean habitats. Additionally, we report in detail the occurrence of the trechaleid genera Enna O. Pickard-Cambridge, 1897, Heidrunea Brescovi...

In vitro-in vivo discord: a preclinical study of AZD2716 and its racemate with comparison to varespladib for the development of snake venom sPLA2 inhibitors

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In vitro-in vivo discord: a preclinical study of AZD2716 and its racemate with comparison to varespladib for the development of snake venom sPLA2 inhibitors

Abstract

We evaluated a family of repurposed sPLA2 inhibitors as novel candidate snakebite envenoming therapeutics. Stereospecific (R)-7 AZD2716 and its racemic mixture were compared to varespladib in an in vitro sPLA2 assay against a sample of 26 venoms from medically important snake species from five continents. All compounds demonstrated potent nano- to picomolar IC50 values, comparable to the benchmark inhibitory profile of varespladib. Surprisingly, however, this in vitro efficacy did not translate to survival in an in vivo mouse model under GLP standard conditions at an independent third party laboratory. In animal rescue studies evaluating both oral and IV dosing against the same four high sPLA2 venoms, varespladib demonstrated more consistent survival duration versus the chirally separated AZD2716 enantiomer and racemate following single-dose intravenous or two-dose oral drug administration. Additionally, the stereospecific AZD2716 did not provide the same survival advantage as the racemic mixture and neither molecule resulted in the same survival advantage as varespladib in vivo (p < 0.05), despite similar in vitro potency. These findings highlight the importance of following in vitro inhibition assays with preclinical studies in drug candidate selection for lead compounds and advancement to clinical development.
Hearth, J. L., Surovtseva, Y., Karjala, Z., Casewell, N. R., Giang, K., & Lewin, M. R. (2026). In vitro-in vivo discord: A preclinical study of AZD2716 and its racemate with comparison to varespladib for the development of snake venom sPLA2 inhibitors. Toxicon: X, 100243. https://doi.org/10.1016/j.toxcx.2026.100243