Last update 19 Sep 2024

KAT2

Last update 19 Sep 2024

Basic Info

Synonyms

2-aminoadipate aminotransferase, 2-aminoadipate transaminase, AADAT

+ [14]

Introduction

Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).

Drugs associated with KAT2

KYN-5356

Target

KAT2

Mechanism

KAT2 inhibitors

Active Org.

Kynexis Therapeutics LLC [+1]

Originator Org.

Mitsubishi Tanabe Pharma Corp.

Active Indication

Cognitive Dysfunction [+1]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

PF-04859989

Target

KAT2

Mechanism

KAT2 inhibitors

Active Org.

Pfizer Inc.

Originator Org.

Pfizer Inc.

Active Indication

Schizophrenia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with KAT2

NCT06225115 / RecruitingPhase 1

A First in Human Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of KYN-5356 in Adult, Healthy Subjects

This first-in-human clinical trial with a randomized, double-blind, placebo-controlled, dose-escalation study design is regarded as standard to test the safety, tolerability, and pharmacokinetics of KYN-5356.
The study comprises 3 parts:
Part 1: Single Ascending Dose study Part 2: Multiple Ascending Dose study Part 3: Food Effect study
The aim of Parts 1 and 2 of the study is to evaluate the safety and tolerability following single and multiple ascending doses of KYN-5356.
The secondary aim is to evaluate the pharmacokinetics (PK) of escalating single and multiple doses of KYN-5356. In Part 2, cerebrospinal fluid will be sampled to explore PK and pharmacodynamic effects of KYN-5356.
The potential effect of food intake on the disposition of KYN-5356 following a single oral dose will be evaluated in Part 3. Part 3 is an open-label, randomized, 2 period, 2 sequence design.

Start Date21 Dec 2023

Sponsor / Collaborator

Kynexis Therapeutics LLC

[+1]

100 Clinical Results associated with KAT2

100 Translational Medicine associated with KAT2

0 Patents (Medical) associated with KAT2

307

Literatures (Medical) associated with KAT2

09 Aug 2024·Science Advances

KAT2A and KAT2B prevent double-stranded RNA accumulation and interferon signaling to maintain intestinal stem cell renewal

Article

Author: Potgieter, Sarah ; Yuan, Zuo-Fei ; Dent, Sharon ; Ellison, Christopher E. ; Woo, Sean ; Lawlor, Matthew ; Halstead, Angela ; Huang, Winston ; Zhao, Caifeng ; Sidoli, Simone ; Pfeffer, Julie ; Yang, Richard ; Nguyen, Mai-Uyen ; Zheng, Haiyan ; Sáenz, José B. ; Iqbal, Jahangir ; Rizly, Rahma ; P. Verzi, Michael

Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in robust activation of interferon signaling and interferon-associated phenotypes including the loss of intestinal stem cells. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and sequencing of immunoprecipitated double-stranded RNA were used to interrogate the mechanism behind this response, which identified mitochondria-encoded double-stranded RNA as the source of intrinsic interferon signaling. Kat2a and Kat2b therefore play an essential role in regulating mitochondrial functions and maintaining intestinal health.

01 Jul 2024·Neuroscience

Impact of Prenatal LPS and Early-life Constant Light Exposure on Circadian Gene Expression Profiles in Various Rat Tissues

Article

Author: Bendová, Zdeňka ; Novotný, Jiří ; Kubištová, Aneta ; Spišská, Veronika

Exposure to lipopolysaccharide (LPS) during prenatal development leads to various changes in neurobiological and behavioural patterns. Similarly, continuous exposure to constant light (LL) during the critical developmental period of the circadian system affects gene expression in various tissues in adulthood. Given the reciprocal nature of the interaction between the circadian and the immune systems, our study primarily investigated the individual effects of both interventions and, more importantly, their combined effect. We aimed to explore whether there might be a potential synergistic effect on circadian rhythms and their parameters, focussing on the expression of clock genes, immune-related genes, and specific genes in the hippocampus, pineal gland, spleen and adrenal gland of rats at postnatal day 30. Our results show a significant influence of prenatal LPS and postnatal LL on the expression profiles of all genes assessed. However, the combination of prenatal LPS and postnatal LL only revealed an enhanced negative effect in a minority of the comparisons. In most cases, it appeared to attenuate the changes induced by the individual interventions, restoring the measured parameters to values closer to those of the control group. In particular, genes such as Nr1d1, Aanat and Tph1 showed increased amplitude in the pineal gland and spleen, while the kynurenine enzymes Kynu and KatII developed circadian rhythmicity in the adrenal glands only after the combined interventions. Our data suggest that a mild immunological challenge during prenatal development may play a critical role in triggering an adaptive response of the circadian clock later in life.

01 Jun 2024·Toxicology Letters

Zinc oxide nanoparticles damage the prefrontal lobe in mouse: Behavioral impacts and key mechanisms

Article

Author: Li, Jun ; Zhang, Dan ; Wang, Tingting ; Wang, Zhiyuan ; Li, Tao ; Xiang, Bo ; Yi, Simeng ; Kang, Xinjiang ; Li, Chang ; Li, Guang ; Deng, Hongmei

Zinc Oxide nanoparticles (ZnO NPs) have dualistic properties due to their advantage and toxicity. However, the impact and mechanisms of ZnO NPs on the prefrontal lobe have limited research. This study investigates the behavioral changes following exposure to ZnO NPs (34 mg/kg, 30 days), integrating multiple behaviors and bioinformatics analysis to identify critical factors and regulatory mechanisms. The essential differentially expressed genes (DEGs) were identified, including ORC1, DSP, AADAT, SLITRK6, and STEAP1. Analysis of the DEGs based on fold change reveals that ZnO NPs primarily regulate cell survival, proliferation, and apoptosis in neural cells, damaging the prefrontal lobe. Moreover, disruption of cell communication, mineral absorption, and immune pathways occurs. Gene set enrichment analysis (GSEA) further shows enrichment of behavior, neuromuscular process, signal transduction in function, synapses-related, cAMP signaling, and immune pathways. Furthermore, alternative splicing (AS) genes highlight synaptic structure/function, synaptic signal transduction, immune responses, cell proliferation, and communication.

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KAT2

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