The Anti-atherogenic Activity of Beauveriolide Derivative BVD327, a Sterol <i>O</i>-Acyltransferase 2-Selective Inhibitor, in Apolipoprotein E Knockout Mice Article Swipe
Taichi Ohshiro
,
Satoshi Imuta
,
Ichiro Hijikuro
,
Hiroaki Yagyu
,
Takashi Takahashi
,
Takayuki Doi
,
Shun Ishibashi
,
Hiroshi Tomoda
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1248/bpb.b19-00913
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1248/bpb.b19-00913
The fungal 13-membered cyclodepsipeptides, beauveriolides I and III, were previously reported to be atheroprotective activity in mouse models via inhibiting sterol O-acyltransferase (SOAT) activity. A total of 149 beauveriolide derivatives (BVDs) synthesized combinatorially were evaluated in in silico absorption, distribution, metabolism and excretion (ADME) analysis and inhibitory activity toward the two SOAT isozymes, SOAT1 and SOAT2. Hence, only 11 BVDs exhibited SOAT2-selective inhibition. Among these, we chose BVD327, which had the highest ADME score, for further evaluation. BVD327 administration (50 mg/kg/d, per os (p.o.)) significantly decreased atherosclerotic lesions in the aorta and heart (25.4 ± 6.9 and 20.6 ± 2.9%, respectively) in apolipoprotein E knockout (Apoe-/-) mice fed a cholesterol-enriched diet (0.2% cholesterol and 21% fat) for 12 weeks. These findings indicate that beauveriolide derivatives can be used as anti-atherosclerotic agents.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1248/bpb.b19-00913
- https://www.jstage.jst.go.jp/article/bpb/43/6/43_b19-00913/_pdf
- OA Status
- diamond
- Cited By
- 4
- References
- 48
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3030310332
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- OpenAlex ID
-
https://openalex.org/W3030310332Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1248/bpb.b19-00913Digital Object Identifier
- Title
-
The Anti-atherogenic Activity of Beauveriolide Derivative BVD327, a Sterol <i>O</i>-Acyltransferase 2-Selective Inhibitor, in Apolipoprotein E Knockout MiceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-05-31Full publication date if available
- Authors
-
Taichi Ohshiro, Satoshi Imuta, Ichiro Hijikuro, Hiroaki Yagyu, Takashi Takahashi, Takayuki Doi, Shun Ishibashi, Hiroshi TomodaList of authors in order
- Landing page
-
https://doi.org/10.1248/bpb.b19-00913Publisher landing page
- PDF URL
-
https://www.jstage.jst.go.jp/article/bpb/43/6/43_b19-00913/_pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
diamondOpen access status per OpenAlex
- OA URL
-
https://www.jstage.jst.go.jp/article/bpb/43/6/43_b19-00913/_pdfDirect OA link when available
- Concepts
-
ADME, Sterol O-acyltransferase, Apolipoprotein B, Cholesterol, Sterol, Chemistry, Apolipoprotein E, Pharmacology, Internal medicine, Endocrinology, Isozyme, Biochemistry, Enzyme, Biology, In vitro, Lipoprotein, Medicine, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
4Total citation count in OpenAlex
- Citations by year (recent)
-
2022: 2, 2020: 2Per-year citation counts (last 5 years)
- References (count)
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48Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.(Apoe<sup>-/-</sup>) | 105 |
| abstract_inverted_index.anti-atherosclerotic | 129 |
| abstract_inverted_index.cholesterol-enriched | 109 |
| cited_by_percentile_year.max | 96 |
| cited_by_percentile_year.min | 94 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 8 |
| citation_normalized_percentile.value | 0.68800717 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |