Journal: bioRxiv

Article Title: Auxin is metabolized through kynurenine in Hypericum perforatum L

doi: 10.64898/2026.05.18.726114

Figure Lengend Snippet: (A) Schematic representation of major tryptophan (Trp)-derived metabolic pathways, including the kynurenine pathway (center), the indole-3-pyruvic acid (IPA)–indole-3-acetic acid (IAA) pathway, and the tryptamine– serotonin–melatonin branch (top). Solid, dashed, and double boxes indicate metabolites reported in animals, plants, or both, respectively. Enzymes are indicated at each step: IDO1/IDO2 (indoleamine 2,3-dioxygenase), TDO (tryptophan 2,3-dioxygenase), AFMID (arylformamidase), KAT (kynurenine aminotransferase), TDC (tryptophan decarboxylase), TAA1/TAR (tryptophan aminotransferase), KYNU (kynureninase), KMO (kynurenine 3-monooxygenase), HAAO (3-hydroxyanthranilate 3,4-dioxygenase), ACMSD (α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase), and QPRT (quinolinate phosphoribosyltransferase). Inhibitor targets are indicated at the corresponding steps: JM6 and RO 61-8048 inhibit KMO, and PF-04859989 inhibits KAT. (B) Chemical structures of the kynurenine pathway metabolites quantified in this study: kynurenine, kynurenic acid (KYNA), and 3-hydroxyanthranilic acid (3-HAA). (C) Chemical structures of the inhibitors used in this study. Core structural differences between JM6 and RO 61-8048 are highlighted in red.

Article Snippet: The compound (R)-3-amino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one (PF-04859989) was identified by a high-throughput screen of the Pfizer compound library as a high-affinity inhibitor of human kynurenine aminotransferase (KAT; ).

Techniques: Derivative Assay

Journal: bioRxiv

Article Title: Auxin is metabolized through kynurenine in Hypericum perforatum L

doi: 10.64898/2026.05.18.726114

Figure Lengend Snippet: ( A) Representative images of explants cultured on MSO (control), kynurenine (KYN), indole-3-acetic acid (IAA), and IAA combined with inhibitors (IAA + JM6, IAA + PF-04859989 [PF], and IAA + RO 61-8048 [RO]). Scale bar = 1 cm (B) Rooting frequency, (C) internodal length (cm per node), (D) root number, and (E) maximum root length (cm) of explants under each treatment. For rooting frequency (B), bars represent mean proportion rooted ± SE. For (C–E), boxplots represent median (center line), interquartile range (box), and range (whiskers). Differences relative to the MSO control were evaluated using Dunnett-adjusted contrasts (p < 0.05; n = 12–18 per treatment).

Article Snippet: The compound (R)-3-amino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one (PF-04859989) was identified by a high-throughput screen of the Pfizer compound library as a high-affinity inhibitor of human kynurenine aminotransferase (KAT; ).

Techniques: Cell Culture, Control

Journal: bioRxiv

Article Title: Auxin is metabolized through kynurenine in Hypericum perforatum L

doi: 10.64898/2026.05.18.726114

Figure Lengend Snippet: (A–C) Representative extracted ion chromatograms (EICs) of PF-04859989 (A), RO 61-8048 (B), and JM6 (KMO inhibitor II) (C) detected in plant tissue by LC–HRMS. Each panel shows the precursor ion trace at the expected m/z and retention time. (D–F) Relative abundance of PF (D), RO (E), and JM6 (F) in roots and shoots following treatment with MSO (control), inhibitor alone, or IAA + inhibitor. Peak areas are shown as log□□-transformed values. Boxplots represent median (center line), interquartile range (box), and range (whiskers). Signals corresponding to each inhibitor were observed in treated tissues and were not detected in MSO controls. Detection was also observed in IAA co-application treatments.

Article Snippet: The compound (R)-3-amino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one (PF-04859989) was identified by a high-throughput screen of the Pfizer compound library as a high-affinity inhibitor of human kynurenine aminotransferase (KAT; ).

Techniques: Control, Transformation Assay

Journal: bioRxiv

Article Title: Auxin is metabolized through kynurenine in Hypericum perforatum L

doi: 10.64898/2026.05.18.726114

Figure Lengend Snippet: Concentrations of (A, D) kynurenic acid (KYNA), (B, E) kynurenine (KYN), and (C, F) 3-hydroxyanthranilic acid (3-HAA) in shoots (A–C) and roots (D–F) of explants cultured on MSO (control), IAA, or IAA combined with kynurenine pathway inhibitors (IAA + JM6, IAA + PF-04859989, and IAA + RO 61-8048). Concentrations are shown as log□□ (ng g −1 FW). Boxplots represent median (center line), interquartile range (box), and range (whiskers). For shoots (A–C), different letters indicate significant differences among treatments (one-way ANOVA followed by Tukey’s HSD, p < 0.05; n = 3). For roots (D–F), differences relative to the MSO control were evaluated using Dunnett-adjusted contrasts (p < 0.05; n = 3).

Article Snippet: The compound (R)-3-amino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one (PF-04859989) was identified by a high-throughput screen of the Pfizer compound library as a high-affinity inhibitor of human kynurenine aminotransferase (KAT; ).

Techniques: Cell Culture, Control

Journal: bioRxiv

Article Title: Auxin is metabolized through kynurenine in Hypericum perforatum L

doi: 10.64898/2026.05.18.726114

Figure Lengend Snippet: Indole-3-acetic acid (IAA) is primarily synthesized from tryptophan through the indole-3-pyruvate (IPyA) pathway via tryptophan aminotransferase (TAA) and YUCCA flavin monooxygenase (YUC). Free IAA may be regulated through conjugation, catabolism, oxidative transformation and through feedback effects on tryptophan-derived metabolism. Kynurenine pathway metabolism proceeds through N-formyl-kynurenine and kynurenine, which occupies a central branch point between kynurenic acid formation via kynurenine aminotransferase (KAT) and downstream oxidative metabolism toward 3-hydroxyanthranilic acid (3-HAA) via kynurenine monooxygenase (KMO). Reactive oxygen species (ROS), temperature, drought, iron, and Fe 2+ are shown as potential stress and redox inputs that may influence auxin and kynurenine-associated metabolism. The pharmacological inhibitors used in this study are shown at their proposed targets: PF-04859989 at KAT, and RO-61-8048 and JM6 at kynurenine monooxygenase (KMO). Dashed arrows indicate proposed interactions linking auxin catabolism or oxidative transformation with kynurenine-associated metabolite accumulation and potential feedback on tryptophan-dependent auxin biosynthesis.

Article Snippet: The compound (R)-3-amino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one (PF-04859989) was identified by a high-throughput screen of the Pfizer compound library as a high-affinity inhibitor of human kynurenine aminotransferase (KAT; ).

Techniques: Synthesized, Conjugation Assay, Transformation Assay, Derivative Assay

Journal: International Journal of Oncology

Article Title: FOXM1 inhibitor, RCM-1, enhances venetoclax mediated apoptosis through downregulation of ATP2B4 in rhabdomyosarcoma

doi: 10.3892/ijo.2026.5865

Figure Lengend Snippet: The combination of RCM1-NP FA and venetoclax decreases tumor growth and enhances caspase-mediated apoptosis in a murine RMS model. (A) Schematic diagram of tumor cells inoculation and treatment. The figure is created in BioRender. Merjaneh, N. (2024) https://BioRender.com/z67t342 . (B) Combination therapy significantly reduced tumor burden compared with vehicle. The mean vehicle tumor volume on day 21 was 685 mm 3 , compared with the average tumor volume of the combination therapy of 361 mm 3 . The maximum tumor diameter was 17.3×11.5 mm and the corresponding maximum tumor volume was 1,144 mm 3 . Tumor volume was measured at different time points during the experiment (P≤0.01; n=12). (C) Combination therapy inhibited proliferation, as indicated by the decreased number of Ki67-positive cells. Combination therapy increased apoptosis, shown by the increased number of (D) BAX-positive cells and (E) the number of caspase3-positive cells compared with single agents and/or vehicle. A total of five random fields per sample were used to quantify the number of Ki67, BAX and cleaved caspase 3 positive cells per group. Values are shown as mean ± SD. Scale bar, 10 μ m. * P≤0.05, ** P≤0.01, **** P≤0.0001. RMS, rhabdomyosarcoma.

Article Snippet: The small molecule compound RCM1 (2-[2-oxo-2-(thiophen-2-yl) ethyl]sulfanyl-4,6-di(thiophen-2-yl) pyridine-3-carbonitrile) was synthesized by Vitas-M Laboratory (95% purity) and dissolved in DMSO for in vitro studies.

Techniques:

Journal: Scientific Reports

Article Title: Protective role of IRG1/itaconate in acute myocardial injury: association with NLRP3 inflammasome and oxidative stress

doi: 10.1038/s41598-026-43821-0

Figure Lengend Snippet: Nrf2 pathway and oxidative stress were associated with IRG1/itaconate in acute myocardial injury. WT or IRG1 KO mice with acute myocardial injury were supplemented with 4-octyl itaconate (4-OI) and sacrificed 18 h post LPS exposure. ( A – D ) The levels of ROS, TBARS, the GSSG/GSH ratioin cardiac tissue homogenates and serum 8-OH-dG concentration were quantified ( n = 8). ( E , F ) Representative western blots and statistical analysis of IL-1β, NLRP3, Keap1, Nrf2, HO-1 and NQO1in heart samples were displayed ( n = 4). Data are representative of two independent experiments and show mean ± SD. ( A – D ) Two-way ANOVA with Sidak multiple comparison test. ( F ) two-sided t -test.

Article Snippet: The compound 4-Octyl itaconate (4-OI, #HY-112675) was sourced from MedChemExpress, USA.

Techniques: Concentration Assay, Western Blot, Comparison