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  • 91
    MedChemExpress riociguat
    ( A ) H & E stained lung histology. Hyperoxia exposure in the presence of placebo decreased radial alveolar count (RAC) ( B ) and increased mean linear intercept (MLI) ( C ) as compared with normoxia. Administration of <t>riociguat</t> increased RAC and decreased MLI during hyperoxia. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 100 μm.
    Riociguat, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 91/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/riociguat/product/MedChemExpress
    Average 91 stars, based on 1 article reviews
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    94
    Selleck Chemicals riociguat
    Differential responses of <t>Riociguat</t> treatment in CCL ‐ and BDL‐induced liver fibrosis. (A) The correlation of the expression of Gucy1a1 and Gucy1b1 in HSCs and PFs. (B) The expression of Gucy1a1 and Gucy1b1 in individual HSCs and portal fibroblasts were overlaid on the UMAP. Dot lines outline the different subclusters according to Figure B. (C) Schematic overview of the experimental design. CCL was injected twice a week for 3 weeks and Riociguat (10 mg/kg body weight) was administered twice a day by oral gavage. Representative images of liver sections from control, CCL ‐, and CCL + Riociguat‐treated mice were stained with sirius red to show the collagen deposit. (D) Sirius red positive area, hydroxyproline concentration, and serum ALT and AST enzymatic activity in the livers of control, CCL ‐, and CCL + Riociguat‐treated mice were quantitated (Corn oil + vehicle, n = 4; CCL + vehicle, n = 6; CCL + Riociguat, n = 6). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001. (E) Schematic overview of the experimental design of the BDL experiment. Vehicle or Riociguat (10 mg/kg body weight) was administered twice a day for 10 days. Representative images of liver sections of vehicle‐ or Riociguat‐treated BDL mice were stained with sirius red. (F) Quantification of sirius red positive area, hydroxyproline concentration, ALT and AST enzymatic activity, and total bilirubin (T‐BIL) concentration in the serum of vehicle‐ or Riociguat‐treated BDL mice (sham + vehicle, n = 4; BDL + vehicle, n = 6; BDL + Riociguat, n = 5). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001.
    Riociguat, supplied by Selleck Chemicals, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Average 94 stars, based on 1 article reviews
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    94
    TargetMol riociguat
    a Domain organization of the human α1β1 sGC heterodimer. The haem cofactor and the GTP substrate-binding site are shown in yellow and blue, respectively. The positions of residues interacting with <t>riociguat</t> are indicated with vertical dark lines. b End-point activity assay of wild-type sGC in the presence or absence of DEA, YC-1, or riociguat as indicated. Mean ± s.d., n = 3 biologically independent reactions. Source data are provided as a . c Cryo-EM map of sGC in complex with NO and riociguat. The densities of haem, riociguat, and GMPCPP are shown in yellow, purple, and blue, respectively. d The cut-open view of ( c ). e Density at the riociguat–binding site. The map is shown as a gray mesh and atomic model is shown as sticks. f Density at the YC-1–binding site. The map is shown as a gray mesh and atomic model is shown as sticks.
    Riociguat, supplied by TargetMol, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/riociguat/product/TargetMol
    Average 94 stars, based on 1 article reviews
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    86
    Bayer AG riociguat
    a Domain organization of the human α1β1 sGC heterodimer. The haem cofactor and the GTP substrate-binding site are shown in yellow and blue, respectively. The positions of residues interacting with <t>riociguat</t> are indicated with vertical dark lines. b End-point activity assay of wild-type sGC in the presence or absence of DEA, YC-1, or riociguat as indicated. Mean ± s.d., n = 3 biologically independent reactions. Source data are provided as a . c Cryo-EM map of sGC in complex with NO and riociguat. The densities of haem, riociguat, and GMPCPP are shown in yellow, purple, and blue, respectively. d The cut-open view of ( c ). e Density at the riociguat–binding site. The map is shown as a gray mesh and atomic model is shown as sticks. f Density at the YC-1–binding site. The map is shown as a gray mesh and atomic model is shown as sticks.
    Riociguat, supplied by Bayer AG, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    86
    Bayer HealthCare Pharmaceuticals Inc riociguat
    a Domain organization of the human α1β1 sGC heterodimer. The haem cofactor and the GTP substrate-binding site are shown in yellow and blue, respectively. The positions of residues interacting with <t>riociguat</t> are indicated with vertical dark lines. b End-point activity assay of wild-type sGC in the presence or absence of DEA, YC-1, or riociguat as indicated. Mean ± s.d., n = 3 biologically independent reactions. Source data are provided as a . c Cryo-EM map of sGC in complex with NO and riociguat. The densities of haem, riociguat, and GMPCPP are shown in yellow, purple, and blue, respectively. d The cut-open view of ( c ). e Density at the riociguat–binding site. The map is shown as a gray mesh and atomic model is shown as sticks. f Density at the YC-1–binding site. The map is shown as a gray mesh and atomic model is shown as sticks.
    Riociguat, supplied by Bayer HealthCare Pharmaceuticals Inc, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/riociguat/product/Bayer HealthCare Pharmaceuticals Inc
    Average 86 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    riociguat - by Bioz Stars, 2023-02
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    Image Search Results


    ( A ) H & E stained lung histology. Hyperoxia exposure in the presence of placebo decreased radial alveolar count (RAC) ( B ) and increased mean linear intercept (MLI) ( C ) as compared with normoxia. Administration of riociguat increased RAC and decreased MLI during hyperoxia. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 100 μm.

    Journal: PLoS ONE

    Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

    doi: 10.1371/journal.pone.0199927

    Figure Lengend Snippet: ( A ) H & E stained lung histology. Hyperoxia exposure in the presence of placebo decreased radial alveolar count (RAC) ( B ) and increased mean linear intercept (MLI) ( C ) as compared with normoxia. Administration of riociguat increased RAC and decreased MLI during hyperoxia. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 100 μm.

    Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

    Techniques: Staining

    ( A ) Immunofluorescence staining for von-Willebrand factor (vWF) (green signal). Vascular density (VD) was determined by counting vWF-positive vessels (<50 μm in diameter) on 10 random high-power field (HPF) images from each lung section. ( B ) Hyperoxia exposure in the presence of placebo significantly decreased VD as compared with normoxia group. Administration of riociguat increased VD in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 50 μm.

    Journal: PLoS ONE

    Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

    doi: 10.1371/journal.pone.0199927

    Figure Lengend Snippet: ( A ) Immunofluorescence staining for von-Willebrand factor (vWF) (green signal). Vascular density (VD) was determined by counting vWF-positive vessels (<50 μm in diameter) on 10 random high-power field (HPF) images from each lung section. ( B ) Hyperoxia exposure in the presence of placebo significantly decreased VD as compared with normoxia group. Administration of riociguat increased VD in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 50 μm.

    Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

    Techniques: Immunofluorescence, Staining

    ( A , C ) Double immunofluorescence staining for vWF (green signal) and α-SMA (red signal) plus DAPI nuclear stain (blue signal). ( B ) Hyperoxia exposure in the presence of placebo increased muscularization of peripheral pulmonary vessels (<50 μm in diameter) as compared with normoxia group (red arrow). Administration of riociguat decreased muscularized vessels in hyperoxia exposed lungs. ( D ) Hyperoxia increased medial wall thickness (MWT) in presence of placebo as compared with normoxia group. Riociguat administration significantly decreased MWT in hyperoxia group. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 50 μm. ( E ) Double immunofluorescence staining with Ki67 (red arrow) and α-SMA (green signal) plus DAPI nuclear staining (blue signal). ( F ) Hyperoxia exposure in the presence of placebo increased vascular proliferation as compared with normoxia group. Administration of riociguat decreased vascular proliferation. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). ( G ) CTGF gene expression was up-regulated by hyperoxia and it was down-regulated by riociguat. * P < 0.05 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). ( H ) Representative Western blots of CTGF and β-actin. ( I ). Expression of CTGF was increased by hyperoxia, while administration of riociguat decreased CTGF expression in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo (n = 6/group). RA: room air, normaxia; O 2 : hyperoxia; PL: placebo; Rio: riociguat.

    Journal: PLoS ONE

    Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

    doi: 10.1371/journal.pone.0199927

    Figure Lengend Snippet: ( A , C ) Double immunofluorescence staining for vWF (green signal) and α-SMA (red signal) plus DAPI nuclear stain (blue signal). ( B ) Hyperoxia exposure in the presence of placebo increased muscularization of peripheral pulmonary vessels (<50 μm in diameter) as compared with normoxia group (red arrow). Administration of riociguat decreased muscularized vessels in hyperoxia exposed lungs. ( D ) Hyperoxia increased medial wall thickness (MWT) in presence of placebo as compared with normoxia group. Riociguat administration significantly decreased MWT in hyperoxia group. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 50 μm. ( E ) Double immunofluorescence staining with Ki67 (red arrow) and α-SMA (green signal) plus DAPI nuclear staining (blue signal). ( F ) Hyperoxia exposure in the presence of placebo increased vascular proliferation as compared with normoxia group. Administration of riociguat decreased vascular proliferation. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). ( G ) CTGF gene expression was up-regulated by hyperoxia and it was down-regulated by riociguat. * P < 0.05 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). ( H ) Representative Western blots of CTGF and β-actin. ( I ). Expression of CTGF was increased by hyperoxia, while administration of riociguat decreased CTGF expression in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo (n = 6/group). RA: room air, normaxia; O 2 : hyperoxia; PL: placebo; Rio: riociguat.

    Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

    Techniques: Double Immunofluorescence Staining, Staining, Expressing, Western Blot

    ( A ) Right ventricular systolic pressure (RVSP) was significantly increased in the hyperoxia + placebo treated group as compared with normoxia group. Riociguat administration significantly decreased RVSP during hyperoxia. *** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo (n = 6/group). ( B ) Right ventricular hypertrophy (RVH), also known as the Fulton’s index, was determined by the weight ratio of right ventricle (RV) to left ventricle + septum (LV + S). Hyperoxia exposed animals in the presence of placebo showed significant RVH as compared with normoxia group. Administration of riociguat decreased RVH in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; ++ P < 0.01 compared with hyperoxia + placebo (n = 6/group).

    Journal: PLoS ONE

    Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

    doi: 10.1371/journal.pone.0199927

    Figure Lengend Snippet: ( A ) Right ventricular systolic pressure (RVSP) was significantly increased in the hyperoxia + placebo treated group as compared with normoxia group. Riociguat administration significantly decreased RVSP during hyperoxia. *** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo (n = 6/group). ( B ) Right ventricular hypertrophy (RVH), also known as the Fulton’s index, was determined by the weight ratio of right ventricle (RV) to left ventricle + septum (LV + S). Hyperoxia exposed animals in the presence of placebo showed significant RVH as compared with normoxia group. Administration of riociguat decreased RVH in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; ++ P < 0.01 compared with hyperoxia + placebo (n = 6/group).

    Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

    Techniques:

    ( A ) Immunostaining for Mac-3, a macrophage marker. ( B ) The alveolar airspace macrophage population was increased by hyperoxia exposure as compared to normoxia. Administration of riociguat decreased macrophage count during hyperoxia. *** P < 0.001 compared with normoxia; ++ P < 0.01 compared with hyperoxia + placebo (n = 6/group). ( C ) Immunostaining for the M1 marker, inducible nitric oxide synthase (iNOS), and M2 markers, chitinase 3-like 3 (Ym1) and resistin-like molecule alpha (RELM-α) showed that in hyperoxia plus placebo lungs, both M1 and M2 polarized macrophages were detected. But, treatment with riociguat decreased only M1 macrophages in hyperoxia-exposed lungs. ( D ) Representative Western blots for NLRP-1, active caspase-1 and active IL-1β. Administration of riociguat decreased hyperoxia-induced lung expression of ( E ) NLRP-1 (*** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo), ( F ) active caspase-1 (*** P < 0.001 compared with normoxia; ++ P < 0.05 compared with hyperoxia + placebo), and ( G ) active IL-1β (* P < 0.05 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo). RA: room air, normoxia; O 2 : hyperoxia; PL: placebo; Rio: riociguat.

    Journal: PLoS ONE

    Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

    doi: 10.1371/journal.pone.0199927

    Figure Lengend Snippet: ( A ) Immunostaining for Mac-3, a macrophage marker. ( B ) The alveolar airspace macrophage population was increased by hyperoxia exposure as compared to normoxia. Administration of riociguat decreased macrophage count during hyperoxia. *** P < 0.001 compared with normoxia; ++ P < 0.01 compared with hyperoxia + placebo (n = 6/group). ( C ) Immunostaining for the M1 marker, inducible nitric oxide synthase (iNOS), and M2 markers, chitinase 3-like 3 (Ym1) and resistin-like molecule alpha (RELM-α) showed that in hyperoxia plus placebo lungs, both M1 and M2 polarized macrophages were detected. But, treatment with riociguat decreased only M1 macrophages in hyperoxia-exposed lungs. ( D ) Representative Western blots for NLRP-1, active caspase-1 and active IL-1β. Administration of riociguat decreased hyperoxia-induced lung expression of ( E ) NLRP-1 (*** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo), ( F ) active caspase-1 (*** P < 0.001 compared with normoxia; ++ P < 0.05 compared with hyperoxia + placebo), and ( G ) active IL-1β (* P < 0.05 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo). RA: room air, normoxia; O 2 : hyperoxia; PL: placebo; Rio: riociguat.

    Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

    Techniques: Immunostaining, Marker, Western Blot, Expressing

    Riociguat significantly increased cGMP concentration in hyperoxia-exposed rats as compared with placebo treated hyperoxic rats. * P < 0.05 compared with hyperoxia + placebo (n = 4/group).

    Journal: PLoS ONE

    Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

    doi: 10.1371/journal.pone.0199927

    Figure Lengend Snippet: Riociguat significantly increased cGMP concentration in hyperoxia-exposed rats as compared with placebo treated hyperoxic rats. * P < 0.05 compared with hyperoxia + placebo (n = 4/group).

    Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

    Techniques: Concentration Assay

    Differential responses of Riociguat treatment in CCL ‐ and BDL‐induced liver fibrosis. (A) The correlation of the expression of Gucy1a1 and Gucy1b1 in HSCs and PFs. (B) The expression of Gucy1a1 and Gucy1b1 in individual HSCs and portal fibroblasts were overlaid on the UMAP. Dot lines outline the different subclusters according to Figure B. (C) Schematic overview of the experimental design. CCL was injected twice a week for 3 weeks and Riociguat (10 mg/kg body weight) was administered twice a day by oral gavage. Representative images of liver sections from control, CCL ‐, and CCL + Riociguat‐treated mice were stained with sirius red to show the collagen deposit. (D) Sirius red positive area, hydroxyproline concentration, and serum ALT and AST enzymatic activity in the livers of control, CCL ‐, and CCL + Riociguat‐treated mice were quantitated (Corn oil + vehicle, n = 4; CCL + vehicle, n = 6; CCL + Riociguat, n = 6). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001. (E) Schematic overview of the experimental design of the BDL experiment. Vehicle or Riociguat (10 mg/kg body weight) was administered twice a day for 10 days. Representative images of liver sections of vehicle‐ or Riociguat‐treated BDL mice were stained with sirius red. (F) Quantification of sirius red positive area, hydroxyproline concentration, ALT and AST enzymatic activity, and total bilirubin (T‐BIL) concentration in the serum of vehicle‐ or Riociguat‐treated BDL mice (sham + vehicle, n = 4; BDL + vehicle, n = 6; BDL + Riociguat, n = 5). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001.

    Journal: Hepatology (Baltimore, Md.)

    Article Title: Single‐Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell–Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice

    doi: 10.1002/hep.31987

    Figure Lengend Snippet: Differential responses of Riociguat treatment in CCL ‐ and BDL‐induced liver fibrosis. (A) The correlation of the expression of Gucy1a1 and Gucy1b1 in HSCs and PFs. (B) The expression of Gucy1a1 and Gucy1b1 in individual HSCs and portal fibroblasts were overlaid on the UMAP. Dot lines outline the different subclusters according to Figure B. (C) Schematic overview of the experimental design. CCL was injected twice a week for 3 weeks and Riociguat (10 mg/kg body weight) was administered twice a day by oral gavage. Representative images of liver sections from control, CCL ‐, and CCL + Riociguat‐treated mice were stained with sirius red to show the collagen deposit. (D) Sirius red positive area, hydroxyproline concentration, and serum ALT and AST enzymatic activity in the livers of control, CCL ‐, and CCL + Riociguat‐treated mice were quantitated (Corn oil + vehicle, n = 4; CCL + vehicle, n = 6; CCL + Riociguat, n = 6). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001. (E) Schematic overview of the experimental design of the BDL experiment. Vehicle or Riociguat (10 mg/kg body weight) was administered twice a day for 10 days. Representative images of liver sections of vehicle‐ or Riociguat‐treated BDL mice were stained with sirius red. (F) Quantification of sirius red positive area, hydroxyproline concentration, ALT and AST enzymatic activity, and total bilirubin (T‐BIL) concentration in the serum of vehicle‐ or Riociguat‐treated BDL mice (sham + vehicle, n = 4; BDL + vehicle, n = 6; BDL + Riociguat, n = 5). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001.

    Article Snippet: For treatment, mice received Riociguat (Selleck, S8135; 10 mg/kg body weight) or vehicle control twice a day via oral gavage.

    Techniques: Expressing, Injection, Staining, Concentration Assay, Activity Assay

    a Domain organization of the human α1β1 sGC heterodimer. The haem cofactor and the GTP substrate-binding site are shown in yellow and blue, respectively. The positions of residues interacting with riociguat are indicated with vertical dark lines. b End-point activity assay of wild-type sGC in the presence or absence of DEA, YC-1, or riociguat as indicated. Mean ± s.d., n = 3 biologically independent reactions. Source data are provided as a . c Cryo-EM map of sGC in complex with NO and riociguat. The densities of haem, riociguat, and GMPCPP are shown in yellow, purple, and blue, respectively. d The cut-open view of ( c ). e Density at the riociguat–binding site. The map is shown as a gray mesh and atomic model is shown as sticks. f Density at the YC-1–binding site. The map is shown as a gray mesh and atomic model is shown as sticks.

    Journal: Nature Communications

    Article Title: Activation mechanism of human soluble guanylate cyclase by stimulators and activators

    doi: 10.1038/s41467-021-25617-0

    Figure Lengend Snippet: a Domain organization of the human α1β1 sGC heterodimer. The haem cofactor and the GTP substrate-binding site are shown in yellow and blue, respectively. The positions of residues interacting with riociguat are indicated with vertical dark lines. b End-point activity assay of wild-type sGC in the presence or absence of DEA, YC-1, or riociguat as indicated. Mean ± s.d., n = 3 biologically independent reactions. Source data are provided as a . c Cryo-EM map of sGC in complex with NO and riociguat. The densities of haem, riociguat, and GMPCPP are shown in yellow, purple, and blue, respectively. d The cut-open view of ( c ). e Density at the riociguat–binding site. The map is shown as a gray mesh and atomic model is shown as sticks. f Density at the YC-1–binding site. The map is shown as a gray mesh and atomic model is shown as sticks.

    Article Snippet: For the sGC in complex with NO and riociguat, 200 µM riociguat (TargetMol), 1 mM GMPCPP, 1 mM DEA NONOate, 5 mM MgCl 2 , 0.5 mM FOM were added to the wild type sGC.

    Techniques: Binding Assay, Activity Assay, Cryo-EM Sample Prep

    a The interactions between YC-1 and sGC. Protein is colored the same as in Fig. . b A 100° rotated view compared to ( a ). c The interactions between riociguat and sGC in the same view as in ( b ). d Cartoon representation of interactions between YC-1 and sGC. Residues from the α1 and β1 subunits are shown as green and cyan, respectively. e Cartoon representation of interactions between riociguat and sGC. Residues are colored the same as in ( d ). f Dose-dependent activation curve of wild type and alanine mutants of sGC in the presence of 1 mM BIC and riociguat at different concentrations ranged from 0.32 mM to 200 mM. Mean ± s.d., n = 3 or 4 independent reactions. Source data are provided as a . g Structure comparison between NO- and riociguat- bound states (colored) and the NO-activated state (gray) at the stimulator-binding site. The conformational changes induced by riociguat binding are indicated by red arrows. h – i Cryo-EM density maps around the sGC stimulators binding site in the NO-activated state ( h ) and NO- and riociguat- bound state ( i ). The residues undergo conformational changes in the two states shown in ( g ) are labeled. j Locations of the α1 D423 and β1 G356 residues in the NO- and riociguat- bound state. The aC atoms of α1 D423 and β1 G356 are shown as red spheres. k End-point activity assay of sGC proline mutations in the absence or presence of 100 mM DEA or 200 mM riociguat. Mean ± s.d., n = 3 independent reactions. Source data are provided as a .

    Journal: Nature Communications

    Article Title: Activation mechanism of human soluble guanylate cyclase by stimulators and activators

    doi: 10.1038/s41467-021-25617-0

    Figure Lengend Snippet: a The interactions between YC-1 and sGC. Protein is colored the same as in Fig. . b A 100° rotated view compared to ( a ). c The interactions between riociguat and sGC in the same view as in ( b ). d Cartoon representation of interactions between YC-1 and sGC. Residues from the α1 and β1 subunits are shown as green and cyan, respectively. e Cartoon representation of interactions between riociguat and sGC. Residues are colored the same as in ( d ). f Dose-dependent activation curve of wild type and alanine mutants of sGC in the presence of 1 mM BIC and riociguat at different concentrations ranged from 0.32 mM to 200 mM. Mean ± s.d., n = 3 or 4 independent reactions. Source data are provided as a . g Structure comparison between NO- and riociguat- bound states (colored) and the NO-activated state (gray) at the stimulator-binding site. The conformational changes induced by riociguat binding are indicated by red arrows. h – i Cryo-EM density maps around the sGC stimulators binding site in the NO-activated state ( h ) and NO- and riociguat- bound state ( i ). The residues undergo conformational changes in the two states shown in ( g ) are labeled. j Locations of the α1 D423 and β1 G356 residues in the NO- and riociguat- bound state. The aC atoms of α1 D423 and β1 G356 are shown as red spheres. k End-point activity assay of sGC proline mutations in the absence or presence of 100 mM DEA or 200 mM riociguat. Mean ± s.d., n = 3 independent reactions. Source data are provided as a .

    Article Snippet: For the sGC in complex with NO and riociguat, 200 µM riociguat (TargetMol), 1 mM GMPCPP, 1 mM DEA NONOate, 5 mM MgCl 2 , 0.5 mM FOM were added to the wild type sGC.

    Techniques: Activation Assay, Binding Assay, Cryo-EM Sample Prep, Labeling, Activity Assay