Why we keep this list
The list
Does SR-17018 have a clinically meaningful therapeutic window in humans?
Oral administration produces respiratory depression in mice. The 'safer than morphine' framing was based largely on intraperitoneal experiments. We don't yet know whether the wider window survives translation to people, and to the only route they actually use.
Is the apparent G-protein bias an artifact of high receptor expression in standard in vitro assays?
Gillis 2020 raised this concern. Many of the canonical bias measurements come from cells engineered to express far more MOR than any neuron. Lower-expression assays make many 'biased' agonists look like ordinary partial agonists.
What is the molecular basis of SR-17018's non-competitive, slowly-reversible binding kinetics?
Stahl 2021 framed SR-17018 as engaging both an orthosteric and an allosteric site. A structural confirmation of an allosteric MOR pocket — and a description of how SR-17018 occupies it — would change how the field thinks about MOR drug design.
By what mechanism does SR-17018 reverse opioid tolerance in animal models?
This is reproducible across labs but mechanistically unexplained. If understood, it could become a research tool for building tolerance-resistant opioids — or for unwinding tolerance in patients on chronic opioid therapy.
Does SR-17018 have utility in any approved-drug development pathway?
The compound itself may never be a drug. But it may be the most useful chemical probe we have for the receptor states that matter for OUD and chronic pain — its primary value may turn out to be as a tool for designing the next compound.
What is its true human pharmacokinetic profile, and how does it differ from rodents?
Rodent half-life is 6–8 hours. Self-reports describe an effective duration of 6–12 hours per oral dose. We do not have any formal human PK data — distribution, metabolism, elimination, drug-drug interactions are all open.
What is the actual prevalence and clinical impact of unregulated human use?
Many forensic toxicology labs do not target SR-17018. Postmortem cases attributable to it could be substantially undercounted. A more complete picture requires both expanded testing in coroner casework and analytical surveillance of the unregulated supply — exactly the gap our testing program aims to help fill.