cb 1  (Chembridge)

Journal: bioRxiv

Article Title: Chemical suppression of a bacterial immune system revives repressed phages

doi: 10.64898/2026.04.28.721336

Figure Lengend Snippet: A. Schematic showing the potential effect of ThsB inhibition on 3′-cADPR signaling. B. Extracted ion chromatograms (EICs) of 3′-cADPR [M–H] − (m/z 540.0424–540.0640) in the lysate of B. subtilis expressing ThsB 0 to 70 minutes after infection with phage SPO1 (MOI = 10). C. The MS/MS spectrum of 3′-cADPR at m/z 404.9987 shows expected fragments. Data were collected in negative ionization mode. D. Biological triplicate measurement of the normalized level of 3′-cADPR in cell lysate 50 min after infection with SPO1. 100 μM of each inhibitor was tested, and their data were normalized to DMSO-treated samples (dashed line). An uninfected “no induction” sample was used as a negative control for signal production. Data are represented as the average ± SEM from three independent biological replicates. Each replicate is displayed with a circle. One-way ANOVA with Dunnett’s multiple comparisons test (single pooled variance) showed no significant difference between any inhibitor and the ‘no inhibitor’ control (adjusted P values: NCI-2, 0.93; CB-1, 0.83; CB-6, 0.43).

Article Snippet: The 3 inhibitors were named using a library-derived prefix (CB: chembridge, NCI: NCI Diversity) followed by a serial number: CB-1, CB-6 and NCI-2 ( ).

Techniques: Inhibition, Expressing, Infection, Tandem Mass Spectroscopy, Negative Control, Control

Journal: bioRxiv

Article Title: Chemical suppression of a bacterial immune system revives repressed phages

doi: 10.64898/2026.04.28.721336

Figure Lengend Snippet: Comparison of the 3′-cADPR binding to the ThsA SLOG domain (PED ID 7UXS chain A ), left panel, to the Boltz-2 modeling largest cluster (middle panel) and Boltz-2 selected model from the largest cluster (cyan) with the best MolModa docking model (orange) (right panel). A. Prediction results for the CB-1 inhibitor, the largest cluster of 57 of 100 Boltz-2 models are shown (middle panel). B. Prediction of NCI-2 binding. The largest cluster of 84 of 100 models predicted by Boltz-2 is shown in the middle panel.

Article Snippet: The 3 inhibitors were named using a library-derived prefix (CB: chembridge, NCI: NCI Diversity) followed by a serial number: CB-1, CB-6 and NCI-2 ( ).

Techniques: Comparison, Binding Assay

Journal: bioRxiv

Article Title: Chemical suppression of a bacterial immune system revives repressed phages

doi: 10.64898/2026.04.28.721336

Figure Lengend Snippet: A: Schematic showing the hypothetical requirement for consistent antiphage immunity to actively repress low levels of phages. Immune suppression would revive ‘persister’ phages. B: Lysis curves of type I Thoeris-expressing B. subtilis infected with SPO1 phage (MOI = 0.01), followed by addition of inhibitor CB-1 (100 µM) after different time delays. See also . C. Schematic showing the hypothetical population lysis resulting from inhibiting the immune system of only some bacteria in a cooperating community. D. Lysis curves of a 1:1 mixture of type I Thoeris-expressing B. subtilis and type II Thoeris-expressing B. subtilis infected with SPO1 phage (MOI = 0.01) and treated with either CB-1 (type I Thoeris inhibitor, 100 µM), IP6C (type II Thoeris inhibitor, 300 µM), or neither (DMSO). E. Lysis curves of a 1:9 and 9:1 mixtures of type I Thoeris-expressing B. subtilis and type II Thoeris-expressing B. subtilis infected with SPO1 phage (MOI = 0.01) and treated with either CB-1 (type I Thoeris inhibitor, 100 µM), IP6C (type II Thoeris inhibitor, 300 µM), or neither (DMSO). In panels B, D, and E, shaded error ranges represent SEM of a biological triplicate.

Article Snippet: The 3 inhibitors were named using a library-derived prefix (CB: chembridge, NCI: NCI Diversity) followed by a serial number: CB-1, CB-6 and NCI-2 ( ).

Techniques: Lysis, Expressing, Infection, Bacteria

Journal: bioRxiv

Article Title: Chemical suppression of a bacterial immune system revives repressed phages

doi: 10.64898/2026.04.28.721336

Figure Lengend Snippet: A–B. Lysis curves of type I Thoeris-expressing B. subtilis infected with SP50 (A, MOI = 0.01) or Goe2 phage (B, MOI = 0.0001), followed by addition of inhibitor CB-1 (100 µM) after different time delays.

Article Snippet: The 3 inhibitors were named using a library-derived prefix (CB: chembridge, NCI: NCI Diversity) followed by a serial number: CB-1, CB-6 and NCI-2 ( ).

Techniques: Lysis, Expressing, Infection

Journal: Molecular Medicine

Article Title: Progressive endocannabinoid system dysregulation in autosomal dominant polycystic kidney disease

doi: 10.1186/s10020-026-01457-w

Figure Lengend Snippet: ECS components are progressively dysregulated in human ADPKD kidney tissue. a Microarray analysis ( GSE7869 ) of human kidney tissue shows stepwise increases in CNR1 transcript from healthy cortex to minimally cystic (PKDm) and fully cystic (PKD) ADPKD tissue, with corresponding reductions in AEA-metabolizing enzymes NAPEPLD and FAAH . b Single-nucleus RNA-sequencing (snRNA-seq) analysis of human ADPKD kidneys ( n = 8) versus healthy controls ( n = 5) demonstrate consistent CNR1 upregulation and marked downregulation of NAPEPLD and FAAH , while 2-AG-metabolizing enzymes remain largely unchanged. c snRNA-seq analysis of diabetic kidney disease (DKD; n = 5 patients; controls n = 6) reveals minimal alterations in CNR1 and ECS-metabolizing enzymes. d Gene expression analysis by qPCR confirms CNR1 upregulation in human ADPKD kidney tissue ( n = 17) versus non-cystic nephrectomy controls ( n = 5), with concurrent changes in ECS enzyme transcription. e-i eCB quantification by liquid chromatography-tandem mass spectrometry (LC–MS/MS) reveals significant depletion of tissue anandamide (AEA); e , N -oleoylethanolamine (OEA); f , 2-arachidonoylglycerol (2-AG); h , and arachidonic acid (AA); i , while N -palmitoylethanolamine (PEA); g remains unchanged. j-l Western blot analysis shows substantial inter-individual variability in CB 1 R protein levels without significant difference between ADPKD ( n = 6) and control kidneys ( n = 4), but significant reductions in DAGLα/β, NAPEPLD, MGLL and FAAH protein. Western blots were normalized to total proteins. Data represent mean ± SEM. Statistics of control versus PKD represented by * and control versus PKDm by #. Statistical significance assessed by Mann–Whitney U test or unpaired t -test: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: Sections were stained with rabbit anti-CB 1 R antibody (1:200, 10006590, Cayman) followed by a goat anti-rabbit HRP conjugate (ImmPRESSTM, Vector laboratories).

Techniques: Microarray, RNA Sequencing, Gene Expression, Liquid Chromatography, Mass Spectrometry, Liquid Chromatography with Mass Spectroscopy, Western Blot, Control, MANN-WHITNEY

Journal: Molecular Medicine

Article Title: Progressive endocannabinoid system dysregulation in autosomal dominant polycystic kidney disease

doi: 10.1186/s10020-026-01457-w

Figure Lengend Snippet: Temporal endocannabinoid system dysregulation during Pkd1 RC/RC disease progression. a-g Quantitative PCR analysis of ECS-related genes across disease stages (9 and 12 months) showing progressive upregulation of Cnr1 a and Cnr2 b transcripts, with corresponding changes in ECS metabolic enzymes: Dagla c , Daglb d , Napepld e , Mgll f , and Faah g . h-n Western blot analysis and quantification of ECS proteins across disease stages, demonstrating sustained CB 1 R protein elevation at 9 and 12 months h, i , stable 2-AG-related enzyme proteins (DAGLα, DAGLβ, MGLL; h, j, k, m ), and stage-specific changes in AEA-related enzymes including elevated NAPEPLD at 12 months ( h, l ) and reduced FAAH at 9 months ( h, n ). Data represent mean ± SEM from WT ( n = 5) and Pkd1 RC/RC ( n = 6–7) per group per timepoint. Statistical analysis: unpaired t -test comparing Pkd1 RC/RC to age-matched WT. Statistical significance: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 versus WT

Article Snippet: Sections were stained with rabbit anti-CB 1 R antibody (1:200, 10006590, Cayman) followed by a goat anti-rabbit HRP conjugate (ImmPRESSTM, Vector laboratories).

Techniques: Biomarker Discovery, Real-time Polymerase Chain Reaction, Western Blot