A Multicenter, Randomized, Double-blinded, Placebo-controlled, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of E1K After Single Dose in Patients With Knee Osteoarthritis

The objective of this study is to evaluate the efficacy and safety of pain relief treatment on knee osteoarthritis when administered E1K or placebo in patients with knee osteoarthritis aged 40 to 70 to determine the optimal dose.

开始日期2022-06-13

申办/合作机构

Ensol Biosciences, Inc.

KCT0006030 / Completed临床1期

A Single-center, Dose Block-Randomized, Double-blinded, Placebo-controlled, Dose-escalation, Phase 1b Clinical Trial to Evaluate the Safety and Tolerability of E1K after Multiple Dose in patients with Osteoarthritis

开始日期2021-07-06

申办/合作机构

Ensol Biosciences, Inc.

KCT0004081 / Completed临床1期

A Single-center, Dose Block-Randomized, Double-blinded, Placebo-controlled, Dose-escalation, Phase 1 clinical trial to evaluate the safety and tolerability of E1K after single dose

开始日期2019-05-27

申办/合作机构

Ensol Biosciences, Inc.

100 项与 Engedi-1000 相关的临床结果

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100 项与 Engedi-1000 相关的转化医学

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100 项与 Engedi-1000 相关的专利（医药）

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项与 Engedi-1000 相关的文献（医药）

2023-03-20·Chemical Research in Toxicology

High-Throughput Screening of ToxCast PFAS Chemical Library for Potential Inhibitors of the Human Sodium Iodide Symporter

Article

作者: Stoker, Tammy E. ; Murr, Ashley S. ; Buckalew, Angela R. ; Wang, Jun ; Bailey, Jarod R.

Over the past decade, there has been increased concern for environmental chemicals that can target various sites within the hypothalamic-pituitary-thyroid axis to potentially disrupt thyroid synthesis, transport, metabolism, and/or function. One well-known thyroid target in both humans and wildlife is the sodium iodide symporter (NIS) that regulates iodide uptake into the thyroid gland, the first step of thyroid hormone synthesis. Our laboratory previously developed and validated a radioactive iodide uptake (RAIU) high-throughput assay in a stably transduced human NIS cell line (hNIS-HEK293T-EPA) to identify chemicals with potential for NIS inhibition. So far, we have tested over 2000 chemicals (US EPA's ToxCast chemical libraries PI_v2, PII, and e1K) and discovered a subset of chemicals that significantly inhibit iodide uptake in the hNIS assay. Here, we utilized this screening assay to test a set of 149 unique per- and polyfluoroalkyl substances (PFAS) (ToxCast PFAS library) for potential NIS inhibition. For this evaluation, the 149 blinded samples were screened in a tiered approach, first in an initial single-concentration (≤100 μM) RAIU assay and subsequent evaluation of the chemicals that produced ≥20% inhibition using multiconcentration (MC) response (0.001-100 μM) testing in parallel RAIU and cell viability assays. Of this set, 38 of the PFAS chemicals inhibited iodide uptake ≥20% in the MC testing with 25 displaying inhibition ≥50%. To prioritize the most potent PFAS NIS inhibitors in this set, chemicals were ranked based on outcomes of both iodide uptake and cytotoxicity and normalized to perchlorate, a known positive control. Consistent with previous findings, PFOS and PFHxS were again found to be potent NIS inhibitors, yet significant inhibition was also observed for several other screened PFAS chemicals. Although further studies are clearly warranted, this initial screening effort identifies NIS as a molecular target for potential thyroid disruption by this persistent and structurally diverse class of chemicals.

2021-05-01·Archives of Toxicology2区 · 医学

Expanded high-throughput screening and chemotype-enrichment analysis of the phase II: e1k ToxCast library for human sodium-iodide symporter (NIS) inhibition

2区 · 医学

Article

作者: Lougee, Ryan R ; Wang, Jun ; Stoker, Tammy E ; Buckalew, Angela R ; Shobair, Mahmoud ; Richard, Ann M ; Laws, Susan C ; Hallinger, Daniel R ; Murr, Ashley S

The sodium-iodide symporter (NIS) mediates the uptake of iodide into the thyroid. Inhibition of NIS function by xenobiotics has been demonstrated to suppress circulating thyroid hormones and perturb related physiological functions. Until recently, few environmental chemicals had been screened for NIS inhibition activity. We previously screened over 1000 chemicals from the ToxCast Phase II (ph1v2 and ph2) libraries using an in vitro radioactive iodide uptake (RAIU) with the hNIS-HEK293T cell line to identify NIS inhibitors. Here, we broaden the chemical space by expanding screening to include the ToxCast e1k library (804 unique chemicals) with initial screening for RAIU at 1 × 10^-4 M. Then 209 chemicals demonstrating > 20% RAIU inhibition were further tested in multiple-concentration, parallel RAIU and cell viability assays. This identified 55 chemicals as active, noncytotoxic RAIU inhibitors. Further cytotoxicity-adjusted potency scoring (with NaClO₄ having a reference score of 200) revealed five chemicals with moderate to strong RAIU inhibition (scored > 100). These data were combined with our previous PhII screening data to produce binary hit-calls for ~ 1800 unique chemicals (PhII + e1k) with and without cytotoxicity filtering. Results were analyzed with a ToxPrint chemotype-enrichment workflow to identify substructural features significantly enriched in the NIS inhibition hit-call space. We assessed the applicability of enriched PhII chemotypes to prospectively predict NIS inhibition in the e1k dataset. Chemotype enrichments derived for the combined ~ 1800 dataset also identified additional enriched features, as well as chemotypes affiliated with cytotoxicity. These enriched chemotypes provide important new information that can support future data interpretation, structure-activity relationship, chemical use, and regulation.

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