Unraveling the rationale and conducting a comprehensive assessment of KD025 (Belumosudil) as a candidate drug for inhibiting adipogenic differentiation—a systematic review

Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 ( Belumosudil ) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiati...

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Published inNaunyn-Schmiedeberg's archives of pharmacology Vol. 397; no. 5; pp. 2681 - 2699
Main Authors Barbalho, Sandra Maria, de Alvares Goulart, Ricardo, Minniti, Giulia, Bechara, Marcelo Dib, de Castro, Marcela Vialogo Marques, Dias, Jefferson Aparecido, Laurindo, Lucas Fornari
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2024
Springer Nature B.V
Subjects
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology
Adipocytes - drug effects
Adipocytes - metabolism
Adipogenesis
Adipogenesis - drug effects
Animals
Biomedical and Life Sciences
Biomedicine
CCAAT/enhancer-binding protein
Cell culture
Cell Differentiation - drug effects
Clinical trials
Fatty acid-binding protein
Fibronectin
Heterocyclic Compounds, 4 or More Rings
Humans
Kinases
Mice
Neurosciences
Peroxisome proliferator-activated receptors
Pharmacology/Toxicology
Protein Kinase Inhibitors - pharmacology
Proteins
Review
Reviews
rho-Associated Kinases - antagonists & inhibitors
rho-Associated Kinases - metabolism
Sterol regulatory element-binding protein
Systematic review
Therapeutic applications
Casein kinase
KD025
Adipocyte differentiation
ROCK2
Rho-associated kinase
Belumosudil
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Abstract Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 ( Belumosudil ) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study’s quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.
AbstractList Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study's quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study's quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.
Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 ( Belumosudil ) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study’s quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.
Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study’s quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.
Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study's quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.
Author Bechara, Marcelo Dib
Dias, Jefferson Aparecido
de Castro, Marcela Vialogo Marques
Minniti, Giulia
Laurindo, Lucas Fornari
Barbalho, Sandra Maria
de Alvares Goulart, Ricardo
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  fullname: de Alvares Goulart, Ricardo
  organization: Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília, Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília
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  fullname: de Castro, Marcela Vialogo Marques
  organization: Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília
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  givenname: Jefferson Aparecido
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  fullname: Dias, Jefferson Aparecido
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  givenname: Lucas Fornari
  surname: Laurindo
  fullname: Laurindo, Lucas Fornari
  email: lucasffffor@gmail.com
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/37966572$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1096_fj_202302716RR
crossref_primary_10_3390_biomedicines12092096
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ISSN 0028-1298
1432-1912
IngestDate Fri Jul 11 10:09:14 EDT 2025
Fri Jul 25 19:56:36 EDT 2025
Mon Jul 21 06:04:32 EDT 2025
Tue Jul 01 02:10:14 EDT 2025
Thu Apr 24 22:57:28 EDT 2025
Fri Feb 21 02:39:09 EST 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
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Issue 5
Keywords Casein kinase
KD025
Adipocyte differentiation
ROCK2
Rho-associated kinase
Belumosudil
Language English
License 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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Snippet Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 ( Belumosudil ) is a newly developed inhibitor that selectively...
Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively...
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SubjectTerms 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology
Adipocytes - drug effects
Adipocytes - metabolism
Adipogenesis
Adipogenesis - drug effects
Animals
Biomedical and Life Sciences
Biomedicine
CCAAT/enhancer-binding protein
Cell culture
Cell Differentiation - drug effects
Clinical trials
Fatty acid-binding protein
Fibronectin
Heterocyclic Compounds, 4 or More Rings
Humans
Kinases
Mice
Neurosciences
Peroxisome proliferator-activated receptors
Pharmacology/Toxicology
Protein Kinase Inhibitors - pharmacology
Proteins
Review
Reviews
rho-Associated Kinases - antagonists & inhibitors
rho-Associated Kinases - metabolism
Sterol regulatory element-binding protein
Systematic review
Therapeutic applications
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Title Unraveling the rationale and conducting a comprehensive assessment of KD025 (Belumosudil) as a candidate drug for inhibiting adipogenic differentiation—a systematic review
URI https://link.springer.com/article/10.1007/s00210-023-02834-6
https://www.ncbi.nlm.nih.gov/pubmed/37966572
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