ArticleInvestigative ophthalmology & visual science2022
Ocular Hypotensive Properties and Biochemical Profile of QLS-101, a Novel ATP-Sensitive Potassium (KATP) Channel Opening Prodrug.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 7 citations in OpenAlex.
- Preclinical Evaluation of Safety and Efficacy of QLS-111: A Novel Formulation of an Adenosine Triphosphate-Sensitive Potassium Channel Opener.Ophthalmology science · 2026Article
- KThe Journal of pharmacology and experimental therapeutics · 2023Article
- Preclinical Pharmacokinetic Profile of Topical Ophthalmic and Intravenous Delivery of QLS-101, a Novel ATP-Sensitive Potassium Channel Opening Ocular Hypotensive Agent.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Purpose: To characterize the ocular hypotensive and pharmacological properties of QLS-101, a novel ATP-sensitive potassium (KATP) channel opening prodrug. Methods: Ocular hypotensive properties of QLS-101 were evaluated by measuring IOP with a handheld rebound tonometer after daily topical ocular instillation of 0.2% (n = 5) or 0.4% QLS-101 (n = 10) in C57BL/6J mice. KATP channel specificity was characterized in HEK-293 cells stably expressing human Kir6.2/SUR2B subunits and assessed for off-target interactions using a receptor binding screen. Conversion of QLS-101 prodrug to its active moiety, levcromakalim, was evaluated in vitro using human ocular tissues and plasma samples and after incubation with human phosphatase enzymes (2.0 nM-1.0 µM). Results: C57BL/6J mice treated once daily with 0.2% QLS-101 exhibited significant (P < 0.01) IOP reductions of 2.1 ± 0.4 mmHg after five days; however, a daily attenuation of the effect was noted by 23h post-dose. By comparison, treatment with 0.4% QLS-101 lowered IOP by 4.8 ± 0.7 mm Hg (P < 0.0001) which was sustained for 24 hours. Unlike levcromakalim, QLS-101 failed to induce KATP channel activity in HEK-Kir6.2/SUR2B cells consistent with its development as a prodrug. No off-target receptor effects were detected with either compound. In vitro ocular tissue conversion of QLS-101 prodrug was identified in human iris, ciliary body, trabecular meshwork, and sclera. Alkaline phosphatase was found to convert QLS-101 (mean Km = 630 µM, kcat = 15 min-1) to levcromakalim. Conclusions: QLS-101 is a novel KATP channel opening prodrug that when converted to levcromakalim shows 24-hour IOP lowering after once-daily topical ocular administration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.