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Unique nonclinical safety profile of PF-06835919, a ketohexokinase inhibitor, highlights a species-dependent mechanism
Zhou, Houle, Geoly et al
Regul Toxicol Pharmacol (2026) 172, 106194 DOI: 10.1016/j.yrtph.2026.106194

Abstract: PF-06835919 is a ketohexokinase inhibitor developed for the treatment of non-alcoholic fatty liver disease and type 2 diabetes. To support its clinical development, nonclinical safety studies in rats up to 6 months and in dogs up to 9 months were conducted. In rat repeat-dose studies, findings consistent with hepatic microsomal enzyme induction (hepatocyte hypertrophy/hyperplasia, with secondary hypertrophy/hyperplasia of thyroid follicular cells and vacuolation of cells in the pars distalis of the pituitary gland) were observed and, in the 6-month study, foci of hepatocellular alteration and thyroid follicular cell adenoma were also noted at higher doses. Other findings included heart weight increase, changes in white and brown fat and serum lipids, decreased/absent corpora lutea in the ovary, and seminiferous tubular degeneration in the testis. None of these findings, except for lower cholesterol and higher heart weight, were present in dog studies. In vitro, PF-06835919 showed little effect on PPAR α, β/δ or γ activities at therapeutic concentrations. It is concluded that PF-06835919 does not directly activate PPARs at exposures achieved at planned clinical doses and most of these rat findings reflect species-specific adaptive changes to liver enzyme induction in addition to the pharmacology of the compound.Copyright © 2026 Elsevier Inc. All rights reserved.

Snippet: Positive controls for PPAR α, β/δ, and γ activation, respectively, were GW590735, GW0742, and rosiglitazone and were supplied with the test kit by Indigo Biosciences (

Human PPARα Reporter Assay Kit Human PPARγ Reporter Assay Kit Human PPARβ/δ Reporter Assay Kit

Individual variation in estrogenic plant consumption predicts fecal estradiol levels in the Ugandan red colobus monkey (Piliocolobus tephrosceles)
Steinbeiser, Chester, Mutegeki et al
Horm Behav (2026) 186, 105998 DOI: 10.1016/j.yhbeh.2026.105998

Abstract: Phytoestrogens are plant secondary compounds that can bind to estrogen receptors and mimic or modulate endogenous estrogen activity, with potential downstream physiological and behavioral effects. To test whether daily variation in wild estrogenic plant consumption was associated with subsequent variation in fecal steroid hormone concentrations, we sequentially followed six individually recognized...

Snippet: Estrogenic activity of extracts was quantified using an estrogen receptor β (ERβ) luciferase reporter assay (Indigo Biosciences, 2020;Chester et al., 2020). Each 96-well plate contained 100 μL of reporter cells and 100 μL of sample, standard, or positive control (in triplicate)

Human ERβ Reporter Assay Kit

Gut Commensal Candida albicans Constrains Whole-Body Energy Storage in Mice
Arrieta, Gutierrez, Nguyen et al
Research Square (2026)

Abstract: Candida albicans is a prevalent member of the gut microbiome and a potent modulator of host immunity, yet its role in metabolic regulation remains unclear. Using gnotobiotic mice colonized with a defined bacterial community (Oligo-MM12) with or without C. albicans, we demonstrate that persistent, non-infectious colonization with this yeast constrains host energy storage and confers resistance to d...

Snippet: FXR activity was quantified using the Mouse Farnesoid X Receptor Reporter Assay System (Indigo Bioscience, USA) according to

Human FXR Reporter Assay Kit Mouse FXR Reporter Assay Kit

Stable simulations do not guarantee functional engagement: a case study of off-target prediction for Seladelpar and Zanamivir
Kemp, Kean, Medvedev
J Comput Aided Mol Des (2026) 40 (1) DOI: 10.1007/s10822-026-00936-w

Abstract: Identifying off-target interactions of approved drugs is important to anticipate side effects and uncover repurposing opportunities. Computational pipelines combining structural homology, structure prediction, and molecular dynamics (MD) simulations offer a promising strategy, but it remains unclear whether stable, control-like MD trajectories reliably indicate functional engagement. We examined t...

Snippet: Reporter assays were performed using commercial engineered mammalian reporter cell lines (Indigo Biosciences, State College, PA, USA). FXR and RARγ were

Human FXR Reporter Assay Kit Human RARγ Reporter Assay Kit Human ERRγ Reporter Assay Kit

Long-Acting RXR Agonism Preserves Retinal Function and Modulates Inflammation in Diabetic Retinopathy
Johnson, Kaffash, Sheini et al
Diabetes (2026) 75 (9), 1554-1567 DOI: 10.2337/db26-0053

Abstract: Diabetic retinopathy (DR) is a leading cause of vision loss and is associated with reduced nuclear retinoid X receptor (RXR) activity. Retinal explants exposed to high glucose showed downregulation of RXR, peroxisome proliferator-activated receptor (PPAR), and liver X receptor-β and their lipid metabolism targets (Abca1, Scd1, and Acox1). Supplementation with the RXR agonist UAB126 restored nuclea...

Snippet: assays were performed to evaluate the activation of PPARα, PPARγ, and LXRα pathways in response to treatment with RXR agonist UAB126 using INDIGO Bioscience

Human PPARα Reporter Assay Kit Human PPARγ Reporter Assay Kit Human LXRα Reporter Assay Kit

Nestorone, a potent progestin, exhibits anti-inflammatory activity and prevents preterm birth in murine models of premature labor
Kumar, Singer, Sachdeva et al
Am J Obstet Gynecol (2026)

Abstract: Preterm birth is the leading cause of neonatal and infant mortality worldwide. Vaginal progesterone reduces the rate of preterm birth by approximately 45% in women with a singleton gestation and a mid-trimester sonographically short cervix, but it is not effective in women with a prior spontaneous preterm birth who do not have cervical shortening. Whether a more potent, next-generation progestin c...

Snippet: one and glucocorticoid receptor transactivation assaysThe transcriptional activity of Nestorone was evaluated using human progesterone and glucocorticoid receptor reporter assays (Indigo Biosciences, State College, PA) to assess its progestational and glucocorticoid-like activity compared to other progestins. Engineered mammalian reporter cell lines expressing full-length human

Human PGR Reporter Assay Kit Human GR Reporter Assay Kit

Investigation of a metabolism-dependent aryl hydrocarbon receptor off-target activation for a drug development candidate and a screening strategy for de-risking backups
Aslamkhan, Kang, Otte et al
Toxicol Sci (2026) 209 (8) DOI: 10.1093/toxsci/kfag083

Abstract: During lead optimization, off-target activation of the aryl hydrocarbon receptor (AhR) was identified for Compound 25. AhR is a xenobiotic-responsive transcription factor associated with adverse outcomes in rodents (and potentially humans) and modulation of drug metabolism. In rats, marked hepatic induction of AhR target genes, Cyp1a1 and Cyp1a2, was observed following repeat dosing and increased ...

Snippet: Immediately prior to assay setup, master stocks were diluted appropriately using compound screening medium (CSM;Indigo Biosciences, State College, PA) to generate 2

Human AhR Reporter Assay Kit

Microbiota-derived 10-hydroxystearic acid activates PPARα to restore gut epithelial barrier integrity and enhance anti-retroviral therapy
Kramer, Santos Rocha, Gaulke et al
Nat Microbiol (2026) 11 (8), 2365-2383 DOI: 10.1038/s41564-026-02433-0

Cited by 2

Abstract: HIV infection disrupts gut epithelial barrier integrity and mucosal immunity, driving chronic inflammation and disease progression which are not fully resolved despite anti-retroviral therapy. Here we identify the microbiota-derived octadecanoid-hydroxy-fatty-acid metabolite 10-hydroxystearic acid (10-HSA), produced by Lactiplantibacillus plantarum, as a key mediator of gut epithelial barrier repa...

Snippet: The experiment was run in triplicate. Luciferase reporter gene assayAssays for determining the activation of PPARα were performed by Indigo Biosciences. Reporter CHO cells used is this study express either the native receptor or a receptor hybrid in which the native N-terminal DNA binding domain (DBD) has been replaced with that of

Human PPARα Reporter Assay Kit

Takeda G-protein-coupled receptor 5 and farnesoid X receptor agonists for diabetes treatment: a patent review and clinical advancements (2015-present)
Sharma, Kumar, Kumar et al
Expert Opin Ther Pat (2026) 36 (7), 593-625 DOI: 10.1080/13543776.2026.2682837

Abstract: Takeda G-protein-coupled receptor 5 (TGR5) and farnesoid X receptor (FXR) are bile acid-activated receptors involved in glucose, lipid, and energy homeostasis, making them promising therapeutic targets for type 2 diabetes mellitus (T2DM) and metabolic liver diseases.This review critically analyzes patents published between 2015 and 2025 retrieved from WIPO Patentscope, Espacenet, USPTO, and Google...

Snippet: In vitro evaluation employed human FXR reporter assays in CHO cells (Indigo Biosciences) and human TGR5 cAMP assays in CHO-K1 cells (DiscoverX), classifying

Human FXR Reporter Assay Kit

Engineering single-dose plasmid DNA for sustained in vivo delivery of designer incretins
Gary, Gao, Hojecki et al
Trends Biotechnol (2026)

Abstract: Incretin mimetic drugs have transformed the treatment of obesity and type 2 diabetes; however, production and patient compliance challenges remain. Plasmid DNA has recently demonstrated the ability to deliver functional monoclonal antibodies for over a year in human patients. We generated plasmid-encoded long-acting incretins (pLincretins) by fusing cleavage-resistant glucagon-like peptide-1 and g...

Snippet: Human GLP-1R Reporter Assay Kit (IB33001) and Human GIP-R Reporter Assay Kit (IB38001) were purchased from Indigo Biosciences and used according to the

Human GIPR Reporter Assay Kit Human GLP-1R Reporter Assay Kit

Discovery of novel chalcone-benzenesulfonamide conjugates as PPARγ agonists: Design, synthesis, and biological evaluation
Ali, Hassan, El Kerdawy et al
Eur J Med Chem (2026) 316, 119024 DOI: 10.1016/j.ejmech.2026.119024

Cited by 1

Abstract: In the present study, a series of novel chalcone-benzenesulfonamides 7a-w was designed and synthesized. Compounds 7a-w were evaluated for their PPARγ ligand binding compared to pioglitazone, and their IC50 (μM) values were determined. The 4-methoxybenzyloxy (unsubstituted)benzenesulfonamide 7o revealed as the most potent PPARγ ligand (IC50 = 1.752 ± 0.04 μM), and high binding affinity (Ki = 54.81 ...

Snippet: Rα/γ/δ reporter assay kits (Cat. No. IB00111, IB00101, and IB00121), respectively, according to the manufacturer's (Indigo Biosciences - US) instructions [19]. The PPARs reporter assays protocol utilized in details is outli

Human PPARα Reporter Assay Kit Human PPARβ/δ Reporter Assay Kit Human PPARγ Reporter Assay Kit

Activity-guided substructure prioritization accelerates discovery of gut microbiota-derived immune-regulating metabolites
Zhao, Chi, Zhang et al
Nat Commun (2026)

Abstract: Gut microbiota exert significant influences on host physiology through bioactive molecules such as indole derivatives. The characteristic aromatic heterocycle substructure shared among various indole derivatives is intrinsically associated with the activation of aryl hydrocarbon receptor (AhR), suggesting a potential structure-activity relationship (SAR). Here, we develop a substructure-activity r...

Snippet: described in Supplementary Method. 1 . Human AhR reporter assay was purchased from INDIGO Biosciences , Inc (PA, USA). LS -180 cell was purchased from ATCC. All analytical reagents are of high - performance liquid chromatograph grade or higher unless otherwise stated

Human AhR Reporter Assay Kit

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