Drug Database
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nicotinic acid (nicotinic acid ER / Niaspanor / Niaspan)

✓ Approved

Merck KGaA · HCAR2 · 小分子

什么是 nicotinic acid?

nicotinic acid 是一种小分子,由Merck KGaA研发。该药已获批,用于治疗相关适应症,给药途径:Oral (PO)。

药物档案

商品名nicotinic acid ER, Niaspanor, Niaspan
公司Merck KGaA
药物类别小分子
分子靶点HCAR2
给药途径Oral (PO)
状态Approved

作用机制

分子靶点

nicotinic acid 作用于 1 个分子靶点:

HCAR2hydroxycarboxylic acid receptor 2 (NIACR1, GPR109A)
需要更深入的分析?Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

nicotinic acid 针对 8 个适应症,涉及 4 个治疗领域。

治疗领域疾病/病症分期
Vascular disordersArteriosclerosis✓ Approved
Metabolism and nutrition disordersHypercholesterolaemia✓ Approved
Metabolism and nutrition disordersHypertriglyceridaemia✓ Approved
Cardiac disordersMyocardial infarction✓ Approved
Metabolism and nutrition disordersDyslipidaemia✓ Approved

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相关研究文献

PubMedJournal of comparative physiology. B, Biochemical, systemic, and environmental physiology2026-07-27

TRP channel activation and cholinergic signaling in insect thermoregulation: evidence from the American cockroach.

Maliszewska Justyna J, Jankowska Milena M, Artkop Marianna M, Rogalska Justyna J

Transient receptor potential (TRP) channels mediate insect thermosensation, yet the downstream neurotransmitter pathways linking TRP activation to behavioral output remain unclear. We investigated the role of nicotinic acetylcholine receptors (nAChRs) in thermoregulatory and neural responses induced by TRP ligands in the American cockroach, Periplaneta americana. Extracellular recordings from the ventral nerve cord showed that capsaicin reduced spontaneous neuronal firing, whereas the selective α7-containing nAChR antagonist MG 624 increased baseline activity. Notably, nicotinic receptor blockade prevented the capsaicin-induced suppression of neuronal activity, suggesting an interaction between cholinergic signaling and capsaicin-induced neuronal modulation. Behaviorally, capsaicin shifted thermal preference toward cooler temperatures, consistent with TRP-mediated heat avoidance. This response, as well as the effect of the TRPV1 antagonist capsazepine, was markedly attenuated by MG 624 pretreatment. Grooming assays revealed differential modulation of antennal and leg grooming, suggesting distinct neural mechanisms and partial interaction between cholinergic and monoaminergic pathways. Despite pronounced neural and behavioral effects, neither TRP ligands nor nicotinic receptor blockade significantly altered whole-animal metabolic rate, as assessed by CO₂ production. Together, these findings indicate that cholinergic signaling contributes to behavioral responses induced by TRP ligands and interacts with capsaicin-induced neuronal modulation in P. americana. The results provide new insight into the neurochemical integration of thermosensory signaling and highlight cholinergic pathways as important contributors to insect thermoregulatory responses.

PMID 42507117
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PubMedInsects2026-07-27

Identification of α6-Containing Nicotinic Acetylcholine Receptors as the Primary Target of Nereistoxin Insecticides and Structural Basis of Channel Blockade.

Gu Licheng L, Liang Yunxin Y, Zhang Boyan B, Huang Jia J et al.

Nereistoxin (NTX) and its derivative insecticides cartap and monosultap have been used for decades to control lepidopteran pests by targeting nicotinic acetylcholine receptors (nAChRs). Unlike neonicotinoid agonists that induce excitatory neurotoxicity, nereistoxin insecticides act as antagonists, blocking cholinergic neurotransmission. However, the molecular target and mechanism of action of these compounds remain incompletely understood. Here, we elucidated the mode of action of cartap and monosultap in Drosophila melanogaster through integrated genetic and computational approaches. Bioassays with Drosophila nAChR subunit mutants demonstrated that the α6 subunit is critically required for insecticidal activity of both compounds, with α6 knockout conferring approximately 10-fold resistance to monosultap and 7-fold resistance to cartap. Molecular docking of protonated NTX into an α6 homopentameric channel model revealed a "dual-anchor" blocking mechanism: the protonated amine forms electrostatic interactions with residue Glu267, while the dithiolane ring creates steric hindrance at residue Thr270. Pore diameter measurements showed an optimal binding cavity of 5.96-6.22 Å in the 267-270 region, narrowing dramatically to 1.64 Å at the deep gate (Ser278), explaining how NTX binding physically occludes the channel. Collectively, these results identify α6-containing nAChRs as the primary target of nereistoxin insecticides and provide a structural framework for understanding channel blockade, with important implications for resistance monitoring and the development of next-generation channel-blocking insecticides.

PMID 42505854
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PubMedMarine drugs2026-07-27

Microbial Community Differentiation and Predicted Chemical-Defense-Related Functional Potential Across Distinct Microhabitats of Cultured Hemicentrotus pulcherrimus.

Li Ding D, Wu Xiaoping X, Yuan Fangyu F, Zhou Fengfang F et al.

Sea urchins harbor diverse microbial communities that may contribute to host-associated ecological interactions, microbial competition, and chemical defense. However, the compartment-specific organization of sea urchin-associated microbiota and their predicted chemical-defense-related functional potential remain poorly understood under aquaculture conditions. In this study, 16S rRNA gene amplicon sequencing was used to characterize microbial communities in rearing water, coelomic fluid, intestine, stomach contents, and surface mucus of Hemicentrotus pulcherrimus (H. pulcherrimus). KEGG Orthology (KO)-based functional prediction was further performed to evaluate predicted chemical-defense-related functional potential, including predicted chemical-defense-related pathways, siderophore-related functions, quorum sensing-related functions, and bacterial competition- and secretion system-related functions. Rarefaction curves and Coverage values indicated sufficient sequencing depth. Alpha diversity and Nonmetric multidimensional scaling (NMDS) analyses revealed clear microbial differentiation among the five sample types, with rearing water showing higher microbial richness. Taxonomic analysis identified Pseudomonadota, Bacteroidota, Campylobacterota, Bacillota, Planctomycetota, and Spirochaetota as dominant phyla, with several discriminative taxa across compartments. KO prediction showed that total predicted abundance of predicted chemical-defense-related KOs differed significantly among sample types. Among host-associated compartments, surface mucus showed relatively higher predicted siderophore-related KO potential, whereas stomach contents showed higher predicted quorum sensing-related KO potential among host-associated compartments. These findings suggest compartment-specific microbial communities and predicted chemical-defense-related functional potential in cultured H. pulcherrimus under aquaculture conditions. Because these functions were inferred from 16S-based KO prediction, they should be interpreted as preliminary hypotheses for future metagenomic, metabolomic, and culture-dependent validation.

PMID 42505983
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PubMedToxins2026-07-27

Integrated Venom Gland Transcriptomic and Venom Proteomic Analyses of the Digger Wasp Cerceris japonica.

Kazuma Kohei K, Tani Naoki N, Konno Katsuhiro K, Kawaguchi Migaku M et al.

Digger wasps are solitary apoid wasps that excavate ground nests and use venom to paralyze insect prey. Recent phylogenetic analyses suggest that digger wasps belong to an ancient lineage of aculeate Hymenoptera and share an evolutionary ancestry with other venomous hymenopterans, including bees and ants. Although the venoms of ants, bees, and social wasps have been extensively studied, those of digger wasps remain poorly characterized in terms of their composition, molecular diversity, and biological activity. In this study, we investigated the venom of the digger wasp Cerceris japonica using integrated transcriptomic and proteomic analyses. We identified 19 toxin-like proteins and peptides, 14 non-toxin-associated components, and 11 novel peptides and proteins with no detectable similarity to known peptides and proteins. Among these, peptide Cj 2 exhibited insecticidal activity but showed no antimicrobial, hemolytic, or nicotinic acetylcholine receptor-modulating activities. These findings provide new insights into the molecular diversity and biological activities of digger wasp venom, expand our understanding of venom evolution in venomous hymenopterans, and serve as a framework for elucidating the conserved and lineage-specific features of hymenopteran venoms.

PMID 42506727
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PubMedPhysical chemistry chemical physics : PCCP2026-07-27

Mechanistic insights into Kv1.6 inhibition by conotoxin Pl14A from molecular dynamics simulation.

Vanneikima, Paul Sandip S

Conotoxins are peptide toxins that are found in marine cone snails and inhibit ion channels with high affinity and selectivity. Pl14A is a conotoxin belonging to the J-superfamily, and is one of a few conotoxins that can inhibit two types of receptors, the Kv1.6 subtype of voltage-gated potassium channels as well as nicotinic acetylcholine receptors (nAChRs). In this work, we use classical molecular dynamics simulations to examine the mechanism of inhibition and structural interactions between Pl14A and the Kv1.6 channel. Our study reveals that Pl14A binds stably in the extracellular vestibule of Kv1.6, engaging key residues within the selectivity filter and turret region through a combination of electrostatic and hydrophobic contacts. The peptide's basic residues, mainly the arginine residue and putative dyad motif Lys18 and Tyr19, are implicated in its subtype specificity and pore-blocking activity. Structural analysis and free energy calculations provide a quantitative view of the conformational changes in both the peptide and the channel, consistent with a pore blocking mode of inhibition. These findings help us to understand the modulation of the Kv1.6 channel by conotoxin Pl14A and offer insight for designing selective peptide inhibitors with therapeutic potential against Kv1.6 related pathologies.

PMID 42506986
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PubMedJournal of fungi (Basel, Switzerland)2026-07-27

Transporter Engineering for Enhancing Citric Acid Production in Aspergillus niger.

Li Jie J, Li Mingyang M, Song Yan Y, Xu Zeyu Z et al.

The efficient industrial production of citric acid by A. niger requires overcoming the limitations of substrate uptake and citrate export on the citrate synthesis efficiency. This study addresses these obstacles using a transporter engineering strategy, modifying the endogenous high-affinity glucose transporter MstF and citrate exporter CexA. The "push-pull" strategy was used to improve citric acid production by increasing glucose import and citrate export. A single overexpression of mstF improved citric acid production, reaching 179.35 g/L in the H7 strain. However, cexA high expression impaired dense mycelium pellet formation and affected the expression of key genes, resulting in reduced citric acid production. For balancing intracellular accumulation and secretion of citrate, simultaneous overexpression of mstF and cexA increased citric acid production and efficiency. In a 30 L fermenter, strain A5 achieved a citric acid titer of 185.91 g/L, a productivity of 3.21 g/h/L, and a shortened fermentation cycle. Collectively, these results provide a reference for the industrial production of citric acid and other organic acids.

PMID 42506234
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