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OtherDrug Discovery and Translational Medicine

The Novel, Clinical Stage Soluble Guanylate Cyclase Activator BI 685509 Protects from Disease Progression in Models of Renal Injury and Disease

Glenn A. Reinhart, Paul C. Harrison, Kathleen Lincoln, Hongxing Chen, Peng Sun, Jon Hill, Hu Sheng Qian, Mark McHugh, Holly Clifford, Khing Jow Ng, Hong Wang, Danielle Fowler, Kristina K. Gueneva-Boucheva, Todd Bosanac, Diane Wong, Ryan M. Fryer, Chris Sarko, Carine M Boustany-Kari and Steven S. Pullen
Journal of Pharmacology and Experimental Therapeutics December 6, 2022, JPET-AR-2022-001423; DOI: https://doi.org/10.1124/jpet.122.001423
Glenn A. Reinhart
1Boehringer Ingelheim Pharmaceuticals, United States
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Paul C. Harrison
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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Kathleen Lincoln
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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Hongxing Chen
3Boehringer Ingelheim Pharmaceuticals, Inc., United States
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Peng Sun
4Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., United States
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Jon Hill
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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Hu Sheng Qian
3Boehringer Ingelheim Pharmaceuticals, Inc., United States
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Mark McHugh
3Boehringer Ingelheim Pharmaceuticals, Inc., United States
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Holly Clifford
3Boehringer Ingelheim Pharmaceuticals, Inc., United States
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Khing Jow Ng
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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Hong Wang
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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Danielle Fowler
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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Kristina K. Gueneva-Boucheva
5DDS, Boehringer-Ingelheim, United States
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Todd Bosanac
6Small Molecule Discovery Researcy, Boehringer-Ingelheim Pharmaceuticals, United States
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Diane Wong
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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Ryan M. Fryer
7Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc, United States
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Chris Sarko
6Small Molecule Discovery Researcy, Boehringer-Ingelheim Pharmaceuticals, United States
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Carine M Boustany-Kari
3Boehringer Ingelheim Pharmaceuticals, Inc., United States
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Steven S. Pullen
2Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharmaceuticals, United States
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  • For correspondence: steven.pullen@boehringer-ingelheim.com
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    • Supplemental Data -

      Supplemental Methods.

      Supplemental Table 1. Mean plasma concentration of BI 685509 after oral administration of 5.83 mg/kg BI 685509 in B6.V-Lep-ob/J mice.

      Supplemental Table 2. Mean plasma concentration of BI 685509 afteri.v. 1 mg/kg and oral 3 mg/kg administration of BI 685509 in wistar han rats.

      Supplemental Table 3.

      Supplemental Fig. 1. General study protocol for UUO and ZSF1 studies indicating relative time for procedures during the course of the 7d or 10wk studies, respectively.

      Supplemental Fig. 2. Mean plasma concentrations of BI 685509 (A) and enalaprilat (B) in ZSF1 rats.

      Supplemental Fig. 3. Effects of BI 685509 and enalapril on body weight and feeding parameters.

      Supplemental Fig. 4. Scatterplot of changes of fold-change between BI 685509 and Vehicle-treated groups in UUO model, comparing 10 mg/kg and 30 mg/kg doses.

      Supplemental Fig. 5. Boxplots of gene expression across groups for urate transporters, Slc14a1, Slc14a2, Upk3a, and Aqp3.

      Supplemental Fig. 6. Heatmap of extracellular-matrix-associated genes upregulated in UUO model and downregulated in groups treated with 10 mg/kg and 30 mg/kg doses of BI 685509.

      Supplemental Fig. 7. Heatmap of podocyte-associated genes decreased in UUO model and upregulated in groups treated with 10 mg/kg and 30 mg/kg doses of BI 685509.

      Supplemental Fig. 8. Scatterplot of the relationship between Col1a1 expression by RNAseq and Sirius Red Morphometry.

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Journal of Pharmacology and Experimental Therapeutics: 385 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 1
1 Apr 2023
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OtherDrug Discovery and Translational Medicine

Kidney protective effects of BI 685509

Glenn A. Reinhart, Paul C. Harrison, Kathleen Lincoln, Hongxing Chen, Peng Sun, Jon Hill, Hu Sheng Qian, Mark McHugh, Holly Clifford, Khing Jow Ng, Hong Wang, Danielle Fowler, Kristina K. Gueneva-Boucheva, Todd Bosanac, Diane Wong, Ryan M. Fryer, Chris Sarko, Carine M Boustany-Kari and Steven S. Pullen
Journal of Pharmacology and Experimental Therapeutics December 6, 2022, JPET-AR-2022-001423; DOI: https://doi.org/10.1124/jpet.122.001423

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OtherDrug Discovery and Translational Medicine

Kidney protective effects of BI 685509

Glenn A. Reinhart, Paul C. Harrison, Kathleen Lincoln, Hongxing Chen, Peng Sun, Jon Hill, Hu Sheng Qian, Mark McHugh, Holly Clifford, Khing Jow Ng, Hong Wang, Danielle Fowler, Kristina K. Gueneva-Boucheva, Todd Bosanac, Diane Wong, Ryan M. Fryer, Chris Sarko, Carine M Boustany-Kari and Steven S. Pullen
Journal of Pharmacology and Experimental Therapeutics December 6, 2022, JPET-AR-2022-001423; DOI: https://doi.org/10.1124/jpet.122.001423
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