BiopestPeptidV1, Main, Exploration, bibRecord, 000481

Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.

Identifieur interne : 000481 ( Main/Exploration ); précédent : 000480; suivant : 000482

Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.

Source :

Journal of medicinal chemistry [ 1520-4804 ] ; 2019.

RBID : pubmed:30694668

Descripteurs français

KwdFr :
- Animaux (MeSH), Calendrier d'administration des médicaments (MeSH), Diabète de type 2 (traitement médicamenteux), Diabète expérimental (traitement médicamenteux), Glucagon-like peptide 1 (sang), Glycémie (analyse), Hypoglycémiants (administration et posologie), Hypoglycémiants (pharmacocinétique), Hypoglycémiants (usage thérapeutique), Inhibiteurs de la dipeptidyl-peptidase IV (administration et posologie), Inhibiteurs de la dipeptidyl-peptidase IV (pharmacocinétique), Inhibiteurs de la dipeptidyl-peptidase IV (usage thérapeutique), Insuline (sang), Produits biologiques (composition chimique), Période (MeSH), Rat Sprague-Dawley (MeSH), Rats (MeSH), Souris (MeSH), Souris de lignée ICR (MeSH).
MESH :
- administration et posologie : Hypoglycémiants, Inhibiteurs de la dipeptidyl-peptidase IV.
- analyse : Glycémie.
- composition chimique : Produits biologiques.
- pharmacocinétique : Hypoglycémiants, Inhibiteurs de la dipeptidyl-peptidase IV.
- sang : Glucagon-like peptide 1, Insuline.
- traitement médicamenteux : Diabète de type 2, Diabète expérimental.
- usage thérapeutique : Hypoglycémiants, Inhibiteurs de la dipeptidyl-peptidase IV.
- Animaux, Calendrier d'administration des médicaments, Période, Rat Sprague-Dawley, Rats, Souris, Souris de lignée ICR.

English descriptors

KwdEn :
- Animals (MeSH), Biological Products (chemistry), Blood Glucose (analysis), Diabetes Mellitus, Experimental (drug therapy), Diabetes Mellitus, Type 2 (drug therapy), Dipeptidyl-Peptidase IV Inhibitors (administration & dosage), Dipeptidyl-Peptidase IV Inhibitors (pharmacokinetics), Dipeptidyl-Peptidase IV Inhibitors (therapeutic use), Drug Administration Schedule (MeSH), Glucagon-Like Peptide 1 (blood), Half-Life (MeSH), Hypoglycemic Agents (administration & dosage), Hypoglycemic Agents (pharmacokinetics), Hypoglycemic Agents (therapeutic use), Insulin (blood), Mice (MeSH), Mice, Inbred ICR (MeSH), Rats (MeSH), Rats, Sprague-Dawley (MeSH).
MESH :
- chemical , administration & dosage : Dipeptidyl-Peptidase IV Inhibitors, Hypoglycemic Agents.
- chemical , analysis : Blood Glucose.
- chemical , blood : Glucagon-Like Peptide 1, Insulin.
- chemical , chemistry : Biological Products.
- drug therapy : Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2.
- chemical , pharmacokinetics : Dipeptidyl-Peptidase IV Inhibitors, Hypoglycemic Agents.
- chemical , therapeutic use : Dipeptidyl-Peptidase IV Inhibitors, Hypoglycemic Agents.
- Animals, Drug Administration Schedule, Half-Life, Mice, Mice, Inbred ICR, Rats, Rats, Sprague-Dawley.

Abstract

Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.

DOI: 10.1021/acs.jmedchem.8b01491
PubMed: 30694668

Affiliations:

République populaire de Chine

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000499
to stream Main, to step Curation: 000499

Le document en format XML

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<author><name sortKey="Li, Honglin" sort="Li, Honglin" uniqKey="Li H" first="Honglin" last="Li">Honglin Li</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.</title>
<author><name sortKey="Li, Shiliang" sort="Li, Shiliang" uniqKey="Li S" first="Shiliang" last="Li">Shiliang Li</name>
<affiliation wicri:level="1"><nlm:affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 </wicri:regionArea>
<wicri:noRegion>Shanghai 200237 </wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Qin, Chun" sort="Qin, Chun" uniqKey="Qin C" first="Chun" last="Qin">Chun Qin</name>
<affiliation wicri:level="1"><nlm:affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 </wicri:regionArea>
<wicri:noRegion>Shanghai 200237 </wicri:noRegion>
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</author>
<author><name sortKey="Cui, Shichao" sort="Cui, Shichao" uniqKey="Cui S" first="Shichao" last="Cui">Shichao Cui</name>
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<affiliation wicri:level="1"><nlm:affiliation>University of Chinese Academy of Sciences , No. 19A Yuquan Road , Beijing 100049 , P. R. China.</nlm:affiliation>
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<author><name sortKey="Xu, Hongling" sort="Xu, Hongling" uniqKey="Xu H" first="Hongling" last="Xu">Hongling Xu</name>
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<author><name sortKey="Wu, Fangshu" sort="Wu, Fangshu" uniqKey="Wu F" first="Fangshu" last="Wu">Fangshu Wu</name>
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<author><name sortKey="Wang, Jiawei" sort="Wang, Jiawei" uniqKey="Wang J" first="Jiawei" last="Wang">Jiawei Wang</name>
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<author><name sortKey="Su, Mingbo" sort="Su, Mingbo" uniqKey="Su M" first="Mingbo" last="Su">Mingbo Su</name>
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<author><name sortKey="Fang, Xiaoyu" sort="Fang, Xiaoyu" uniqKey="Fang X" first="Xiaoyu" last="Fang">Xiaoyu Fang</name>
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<author><name sortKey="Li, Dan" sort="Li, Dan" uniqKey="Li D" first="Dan" last="Li">Dan Li</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Drug Research , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 </wicri:regionArea>
<wicri:noRegion>Shanghai 201203 </wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jiao, Qian" sort="Jiao, Qian" uniqKey="Jiao Q" first="Qian" last="Jiao">Qian Jiao</name>
<affiliation wicri:level="1"><nlm:affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 </wicri:regionArea>
<wicri:noRegion>Shanghai 200237 </wicri:noRegion>
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<author><name sortKey="Zhang, Ming" sort="Zhang, Ming" uniqKey="Zhang M" first="Ming" last="Zhang">Ming Zhang</name>
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<author><name sortKey="Wang, Rui" sort="Wang, Rui" uniqKey="Wang R" first="Rui" last="Wang">Rui Wang</name>
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<author><name sortKey="Li, Jia" sort="Li, Jia" uniqKey="Li J" first="Jia" last="Li">Jia Li</name>
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<author><name sortKey="Zhao, Zhenjiang" sort="Zhao, Zhenjiang" uniqKey="Zhao Z" first="Zhenjiang" last="Zhao">Zhenjiang Zhao</name>
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<author><name sortKey="Li, Honglin" sort="Li, Honglin" uniqKey="Li H" first="Honglin" last="Li">Honglin Li</name>
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<series><title level="j">Journal of medicinal chemistry</title>
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<term>Biological Products (chemistry)</term>
<term>Blood Glucose (analysis)</term>
<term>Diabetes Mellitus, Experimental (drug therapy)</term>
<term>Diabetes Mellitus, Type 2 (drug therapy)</term>
<term>Dipeptidyl-Peptidase IV Inhibitors (administration & dosage)</term>
<term>Dipeptidyl-Peptidase IV Inhibitors (pharmacokinetics)</term>
<term>Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)</term>
<term>Drug Administration Schedule (MeSH)</term>
<term>Glucagon-Like Peptide 1 (blood)</term>
<term>Half-Life (MeSH)</term>
<term>Hypoglycemic Agents (administration & dosage)</term>
<term>Hypoglycemic Agents (pharmacokinetics)</term>
<term>Hypoglycemic Agents (therapeutic use)</term>
<term>Insulin (blood)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred ICR (MeSH)</term>
<term>Rats (MeSH)</term>
<term>Rats, Sprague-Dawley (MeSH)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Calendrier d'administration des médicaments (MeSH)</term>
<term>Diabète de type 2 (traitement médicamenteux)</term>
<term>Diabète expérimental (traitement médicamenteux)</term>
<term>Glucagon-like peptide 1 (sang)</term>
<term>Glycémie (analyse)</term>
<term>Hypoglycémiants (administration et posologie)</term>
<term>Hypoglycémiants (pharmacocinétique)</term>
<term>Hypoglycémiants (usage thérapeutique)</term>
<term>Inhibiteurs de la dipeptidyl-peptidase IV (administration et posologie)</term>
<term>Inhibiteurs de la dipeptidyl-peptidase IV (pharmacocinétique)</term>
<term>Inhibiteurs de la dipeptidyl-peptidase IV (usage thérapeutique)</term>
<term>Insuline (sang)</term>
<term>Produits biologiques (composition chimique)</term>
<term>Période (MeSH)</term>
<term>Rat Sprague-Dawley (MeSH)</term>
<term>Rats (MeSH)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée ICR (MeSH)</term>
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<term>Hypoglycemic Agents</term>
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<term>Insulin</term>
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<term>Inhibiteurs de la dipeptidyl-peptidase IV</term>
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<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Produits biologiques</term>
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<term>Diabetes Mellitus, Type 2</term>
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<term>Inhibiteurs de la dipeptidyl-peptidase IV</term>
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<term>Hypoglycemic Agents</term>
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<term>Insuline</term>
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<term>Hypoglycemic Agents</term>
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<term>Diabète expérimental</term>
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<term>Inhibiteurs de la dipeptidyl-peptidase IV</term>
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<term>Drug Administration Schedule</term>
<term>Half-Life</term>
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<term>Rats, Sprague-Dawley</term>
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<term>Période</term>
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<front><div type="abstract" xml:lang="en">Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.</div>
</front>
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<DateCompleted><Year>2020</Year>
<Month>04</Month>
<Day>13</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>04</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4804</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>62</Volume>
<Issue>5</Issue>
<PubDate><Year>2019</Year>
<Month>03</Month>
<Day>14</Day>
</PubDate>
</JournalIssue>
<Title>Journal of medicinal chemistry</Title>
<ISOAbbreviation>J Med Chem</ISOAbbreviation>
</Journal>
<ArticleTitle>Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.</ArticleTitle>
<Pagination><MedlinePgn>2348-2361</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1021/acs.jmedchem.8b01491</ELocationID>
<Abstract><AbstractText>Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Shiliang</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">0000-0003-4414-237X</Identifier>
<AffiliationInfo><Affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Qin</LastName>
<ForeName>Chun</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cui</LastName>
<ForeName>Shichao</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Drug Research , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 , China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University of Chinese Academy of Sciences , No. 19A Yuquan Road , Beijing 100049 , P. R. China.</Affiliation>
</AffiliationInfo>
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<Initials>H</Initials>
<AffiliationInfo><Affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</Affiliation>
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<Initials>F</Initials>
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</AffiliationInfo>
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<ForeName>Jiawei</ForeName>
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</AffiliationInfo>
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<ForeName>Qian</ForeName>
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<Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Zhenjiang</ForeName>
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<AffiliationInfo><Affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
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<AffiliationInfo><Affiliation>University of Chinese Academy of Sciences , No. 19A Yuquan Road , Beijing 100049 , P. R. China.</Affiliation>
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<AffiliationInfo><Affiliation>Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.</Affiliation>
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<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>4</Month>
<Day>14</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2019</Year>
<Month>1</Month>
<Day>30</Day>
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<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">30694668</ArticleId>
<ArticleId IdType="doi">10.1021/acs.jmedchem.8b01491</ArticleId>
</ArticleIdList>
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<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Shiliang" sort="Li, Shiliang" uniqKey="Li S" first="Shiliang" last="Li">Shiliang Li</name>
</noRegion>
<name sortKey="Cui, Shichao" sort="Cui, Shichao" uniqKey="Cui S" first="Shichao" last="Cui">Shichao Cui</name>
<name sortKey="Cui, Shichao" sort="Cui, Shichao" uniqKey="Cui S" first="Shichao" last="Cui">Shichao Cui</name>
<name sortKey="Fang, Xiaoyu" sort="Fang, Xiaoyu" uniqKey="Fang X" first="Xiaoyu" last="Fang">Xiaoyu Fang</name>
<name sortKey="Jiang, Hualiang" sort="Jiang, Hualiang" uniqKey="Jiang H" first="Hualiang" last="Jiang">Hualiang Jiang</name>
<name sortKey="Jiao, Qian" sort="Jiao, Qian" uniqKey="Jiao Q" first="Qian" last="Jiao">Qian Jiao</name>
<name sortKey="Li, Dan" sort="Li, Dan" uniqKey="Li D" first="Dan" last="Li">Dan Li</name>
<name sortKey="Li, Honglin" sort="Li, Honglin" uniqKey="Li H" first="Honglin" last="Li">Honglin Li</name>
<name sortKey="Li, Jia" sort="Li, Jia" uniqKey="Li J" first="Jia" last="Li">Jia Li</name>
<name sortKey="Li, Jingya" sort="Li, Jingya" uniqKey="Li J" first="Jingya" last="Li">Jingya Li</name>
<name sortKey="Li, Jingya" sort="Li, Jingya" uniqKey="Li J" first="Jingya" last="Li">Jingya Li</name>
<name sortKey="Qin, Chun" sort="Qin, Chun" uniqKey="Qin C" first="Chun" last="Qin">Chun Qin</name>
<name sortKey="Su, Mingbo" sort="Su, Mingbo" uniqKey="Su M" first="Mingbo" last="Su">Mingbo Su</name>
<name sortKey="Wang, Jiawei" sort="Wang, Jiawei" uniqKey="Wang J" first="Jiawei" last="Wang">Jiawei Wang</name>
<name sortKey="Wang, Rui" sort="Wang, Rui" uniqKey="Wang R" first="Rui" last="Wang">Rui Wang</name>
<name sortKey="Wu, Fangshu" sort="Wu, Fangshu" uniqKey="Wu F" first="Fangshu" last="Wu">Fangshu Wu</name>
<name sortKey="Xia, Chunmei" sort="Xia, Chunmei" uniqKey="Xia C" first="Chunmei" last="Xia">Chunmei Xia</name>
<name sortKey="Xu, Hongling" sort="Xu, Hongling" uniqKey="Xu H" first="Hongling" last="Xu">Hongling Xu</name>
<name sortKey="Zhang, Ming" sort="Zhang, Ming" uniqKey="Zhang M" first="Ming" last="Zhang">Ming Zhang</name>
<name sortKey="Zhao, Zhenjiang" sort="Zhao, Zhenjiang" uniqKey="Zhao Z" first="Zhenjiang" last="Zhao">Zhenjiang Zhao</name>
<name sortKey="Zhu, Lili" sort="Zhu, Lili" uniqKey="Zhu L" first="Lili" last="Zhu">Lili Zhu</name>
</country>
</tree>
</affiliations>
</record>

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   |wiki=    Bois
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   |texte=   Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.
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Serveur d'exploration sur les peptides biopesticides

Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.

Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.

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