Ask about this productRelated genes to: OXER1 antibody
- Gene:
- OXER1 NIH gene
- Name:
- oxoeicosanoid receptor 1
- Previous symbol:
- -
- Synonyms:
- GPCR, TG1019, GPR170
- Chromosome:
- 2p21
- Locus Type:
- gene with protein product
- Date approved:
- 2004-04-02
- Date modifiied:
- 2016-10-05
Related products to: OXER1 antibody
Related articles to: OXER1 antibody
- GPR81 (HCAR1) is a lactate-sensing G protein-coupled receptor (GPCR) involved in tumor progression, immune evasion, and therapeutic resistance across various cancers. Despite their clinical relevance and druggable nature, selective HCAR1 antagonists have yet to be identified. This study aimed to construct a statistically significant Support Vector Machine (SVM) model for binary classification (agonists versus antagonists) of HCAR1's potential ligands and the prioritization of molecular substructures driving antagonism and receptor selectivity. An SVM model was trained on 144 ligands (66 agonists, 78 antagonists), listed in the IUPHAR/BPS Guide to Pharmacology, from 12 structurally related Class A GPCRs (HCAR1, HCAR2, HCAR3, OXER1, GPR35, SUCNR1, P2Y2, MCHR1, OPRD1, AGTR1, ADORA2A, and ADRA1A). Their ligands were encoded using physicochemical descriptors, 2048-bit ECFP4 fingerprints, and ΔAffinity scores from molecular docking to active and inactive receptor conformations. The data set was split 80/20 for training and testing, respectively, with hyperparameters (, γ) being optimized via 5-fold cross-validation. SHAP analysis was performed for feature interpretation. The final SVM model achieved a test set accuracy of 79.3%, with a sensitivity of 69.2% and specificity of 87.5%. The ROC analysis yielded an AUC of 0.94, while bootstrapping confirmed robust performance with a mean AUC of 0.874 and a 95% confidence interval [0.711, 1.000]. SHAP analysis highlighted polar, rigid, and aromatic substructures as selectivity-driving features. We applied the model to screen 3,377 compounds from natural products, synthetic libraries, and FDA-approved drugs, prioritizing potential HCAR1 ligands with antagonist-like features. Based on ΔAffinity, off-target scores, and prediction confidence, Ketanserin, Cryptopyranmoscatone A1 diacetate, and Cefuroxime emerged as reference ligands with promising antagonistic potential, two of which are FDA-approved drugs. Rather than representing final hits, these molecules illustrate how structural and electronic features can favor the stabilization of inactive states in HCAR1. Overall, this work presents a proof-of-concept framework that integrates conformational docking, machine learning, and substructure interpretation to elucidate the chemical and structural determinants of HCAR1 antagonism. The findings provide fragment-level insights that may guide future bioisosteric and fragment-based design of selective antagonists for lactate-driven tumors. - Source: PubMed
Publication date: 2026/02/03
Carvalho Letícia VivasSeyffert NúbiaMeyer RobertoTiwari SandeepCastro Thiago Luiz de Paula - The treatment and prevention of bronchial asthma continue to present significant challenges. Mendelian randomization (MR) has been extensively employed to identify novel therapeutic targets. Consequently, we conducted a systematic MR analysis across the druggable genome to identify potential therapeutic targets for asthma. - Source: PubMed
Publication date: 2026/01/21
Wang HaijiaoZhang PengYu HongpengShi LiWang Tan - Hepatoblastoma (HB) is a rare embryonal liver tumor, with an increasing global incidence that underscores the need to understand its genetic etiology. - Source: PubMed
Xie TiankaiSorenson Josey CSpector Logan GPankratz NathanHuang R StephanieHiyama EisoPoynter Jenny NTomlinson Gail EArmengol CarolinaKappler RolandScheurer Michael ERoman EveCastellano AuroraGrotzer Michael AZiegler David SBasu SaonliMarcotte Erin LYang Tianzhong - During the innate immune response at epithelial wound sites, oxidative stress acts microbicidal and-mechanistically less well understood-as an immune and resilience signal. The reversible sulfhydryl (SH) oxidation of kinases, phosphatases, and transcription factors constitute the perhaps best-known redox signalling paradigm, whereas mechanisms that transduce metabolic redox cues, such as redox cofactor balance, remain little explored. Here, using mammalian cells, microsomes, and live zebrafish, we identify DHRS7, a short-chain fatty acid dehydrogenase/reductase (SDR), as conserved, 5-hydroxyeicosanoid dehydrogenase (5-HEDH). Under oxidative stress, DHRS7 consumes NADP to convert arachidonic acid (AA)-derived 5(S)-HETE into the inflammatory lipid 5-KETE, which activates leukocyte chemotaxis via the OXER1 receptor. While Dhrs7 acts as a NADPH-dependent 5-KETE sink in unstressed, healthy tissue, it promotes rapid, 5-KETE dependent leukocytic inflammation in wounded zebrafish skin. Thus, DHRS7 epitomizes an underappreciated mode of redox signalling-beyond classic SH oxidation-that leverages NADPH metabolism to generate or quench a paracrine lipid signal. Metabolic redox sensors like DHRS7 might be promising therapeutic targets in diseases characterized by disturbed redox balance. - Source: PubMed
Publication date: 2025/02/08
Ma YananHui King LamAmbaw Yohannes AWalther Tobias CFarese Robert VLengyel MiklosGelashvili ZazaLu DajunNiethammer Philipp - Generation of reactive oxygen species is an important part of the innate immune response. Generating microbicidal levels of reactive oxygen species (ROS) requires adaptation of mucosal barriers. High tolerance of ROS provides improved innate immune defenses against pathogens, whereas low tolerance renders host cells prone to chronic toxicity and mutagenesis, which can promote inflammation (e.g., in asthma and Crohn's disease) and cancerogenesis. The mechanisms that sense and mediate host tolerance to ROS are little understood. In this study, we discover an unexpected role for the redox-sensitive, chemokine-like lipid 5-oxo-eicosatetraenoic acid (5-KETE) in redox adaptation. 5-KETE is known to attract leukocytes to damaged/infected mucosal barriers by signaling through its receptor, OXER1. Suggestive of a distinct non-immune function, we here report that the loss of the OXER1 ortholog Hcar1-4 causes barrier defects and baseline inflammation in the intestine of live zebrafish larvae. In zebrafish and cultured human cells, OXER1 signaling protects against oxidative nucleotide lesions by inducing DNA-protective Nudix hydrolases. Our data reveal the oxoeicosanoid pathway as a conserved ROS resilience mechanism that fortifies pathogen-exposed mucosal linings against increased oxidative stress . - Source: PubMed
Publication date: 2025/02/08
Lengyel MiklosMa YananGelashvili ZazaPeng SiyangQuraishi MeysoonNiethammer Philipp