Ortholog Kits and Services
Many labs are interested in cross-species comparisons, especially contrasting human nuclear receptor activity to common laboratory animals. Determining a drug candidate’s cross-activity with human xenobiotic-sensing receptors provides important early indications of that drug’s potential for downstream drug-drug interactions. With more than 30 ortholog kits and services available, INDIGO’s assay solutions provide the critical data you need, while lowering the time, cost, and risk associated with drug discovery.
Pre-clinical studies utilize animals as human surrogates to assess a drug’s pharmacokinetic and toxicologic profiles. These studies are often confounded by the fact that the ligand preferences and response dynamics can vary dramatically between the human receptor and the corresponding ortholog receptors, with even the receptors of closely related species, such as mouse and rat, sometimes exhibiting dramatically different ligand preferences and responses. This creates a challenge when selecting the most human-relevant animal model for pre-clinical studies.
With animal studies required by the FDA, selecting the animal model that provides the most representative human-surrogate is critical to assessing a potential drug’s likelihood of unwanted effects. This is why cell-based assay models are crucial to help make this determination prior to entering ADMET studies.
With more than 30 ortholog assays - including rat, mouse, dog, monkey, and zebrafish - available as kits and/or services, and others available for custom development, INDIGO helps researchers screen the right animal, before trial.
What to know more about choosing the right ortholog model? Find more information on profiling drug activity of human and ortholog xenobiotic-sensing receptors in this scientific poster. or view related articles in the Related Articles tab.
Discovery and development research depends on reliable, high-performing assays designed to meet your needs. INDIGO currently offers numerous ortholog nuclear receptor assays in rat, mouse, dog, non-human primate, and zebrafish, though if you need an assay for a species or nuclear receptor not currently available, our services lab can clone and optimize an assay for your research.
We supplement the world’s largest portfolio of nuclear receptor assay kits and services and in vitro toxicology solutions with greater results readability, reproducibility, and faster turnaround times. Our custom assay kit solutions, plus supportive team and reliable science and platforms aim to reduce time, cost, and risk associated with the discovery process. Contact us today and Request a Quote to discuss your research needs.
Species Differences in Pregnane X Receptor Activation: Examination of common laboratory animal species
INTRODUCTION Nuclear receptors (NRs) are ligand-dependent transcription factors found in many species that regulate the expression of important target genes involved in a spectrum of developmental and physiological processes. In addition to ligand binding, the transcriptional activities of NRs are also modulated through a range of protein-protein interactions with coregulatory proteins, either with coactivator or
Expansion Meets Industry Demand for Pre-Clinical Models for Cancer and Environmental Research State College, PA (23 January 2020) – INDIGO Biosciences, the recognized industry leader in nuclear receptor research, has announced the addition of four zebrafish assays to its portfolio. These additions both expand INDIGO’s robust portfolio of in vitro animal model assay systems and
Identifying qualitative differences in PPARα signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods
ABSTRACT In this paper, we evaluate the PPARα signaling network in rats, examining transcriptional responses in primary hepatocytes exposed to a PPARα specific ligand, GW7647. These transcriptomic studies were complemented with ChIP-seq studies of PPARα binding and transcription binding motif identification for PPARα responsive genes. We also conducted a limited study of GW7647 dosing the in
Quinazolinone derivative BNUA‐3 ameliorated [NDEA+2‐AAF]‐ induced liver carcinogenesis in SD rats by modulating AhR‐CYP1B1‐Nrf2‐Keap1 pathway
ABSTRACT Cytochrome P450 1B1, considered as one of the novel chemotherapeutic targets involved in cancer prevention and therapy is also associated with the conversion of procarcinogens into their active metabolites. The aryl hydrocarbon receptor (AhR) is responsible for mediating different biological responses to a wide variety of environmental pollutants and also causes transcriptional activation of
ABSTRACT Takeda G protein-coupled receptor 5 (TGR5) agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L cells, a potentially therapeutic action against metabolic diseases such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and Type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects, including inhibition of gallbladder emptying.
Involvement of estrogen receptor α in pro-pruritic and pro-inflammatory responses in a mouse model of allergic dermatitis
ABSTRACT It has been reported that endogenous or exogenous estrogens can affect the immune system, resulting in immune disorders; however, their direct involvement in such conditions remains to be demonstrated. The purpose of this study was to investigate whether estrogen receptors (ER) are directly implicated in pro-pruritic and pro-inflammatory reactions in cutaneous allergy. Initially, enhancement of the pro-inflammatory
Bitter melon seed oil increases mitochondrial content in gastrocnemius muscle and improves running endurance in sedentary C57BL/6 J mice
ABSTRACT The α-eleostearic acid (α-ESA) in bitter melon seed oil (BMSO) is efficiently converted by the body into rumenic acid. The objective of this study was to investigate effects of BMSO on skeletal muscle fiber-type switch and endurance capacity in mice, with or without exercise training. In a 3 x 2 factorial design, C57BL/6 J
Disruption of Nuclear Receptor Signaling Alters Triphenyl Phosphate-Induced Cardiotoxicity in Zebrafish Embryos
ABSTRACT Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on (1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and (2) high-content screening to identify nuclear receptor ligands that
Sedaxane—Use of Nuclear Receptor Transactivation Assays, Toxicogenomics, and Toxicokinetics as Part of a Mode of Action Framework for Rodent Liver Tumors
ABSTRACT Experimental data demonstrate a mode of action (MOA) for liver tumors in male rats and mice treated with sedaxane that starts with activation of CAR, followed by altered expression of CAR-responsive genes, increased cell proliferation, and eventually clonal expansion of preneoplastic cells, leading to the development of altered foci and tumors. This MOA is
Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats is not Attenuated by Dietary Choline Supplementation
ABSTRACT Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for four weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation