PMID- 32468873
OWN - NLM
STAT- MEDLINE
DCOM- 20210108
LR  - 20210108
IS  - 2169-141X (Electronic)
IS  - 2169-1401 (Linking)
VI  - 48
IP  - 1
DP  - 2020 Dec
TI  - Everestmab, a novel long-acting GLP-1/anti GLP-1R nanobody fusion protein, exerts 
      potent anti-diabetic effects.
PG  - 854-866
LID - 10.1080/21691401.2020.1770268 [doi]
AB  - In the present study, a novel single domain antibody (sdAb) fusion protein, named 
      everestmab, composing of a mutated GLP-1(A8G) fused to the tandem bispecific 
      humanized GLP-1R-targeting and albumin-binding nanobodies was designed and 
      characterized for the therapies for type 2 diabetes mellitus (T2DM). Surface 
      plasmon resonance (SPR) measurements demonstrated everestmab associates with 
      serum albumins of rat and monkey species with high affinity, and tends to be 
      cross-reactive with rat and monkey species. In vitro GLP-1R binding and 
      activation assays revealed that everestmab can specifically activate the GLP-1R, 
      and the antagonist exendin-4 (9-39) did not inhibit the activation yet. In vivo 
      multiple oral glucose tolerance tests (OGTTs) and hypoglycaemic efficacy tests 
      proved that a single injection of everestmab reduced the blood glucose for at 
      least 144 h in Goto-Kakizaki (GK) rats. The plasma half-lives of 4.1 and 7.8 days 
      were observed after a single s.c. administration of everestmab in SD rats and 
      cynomolgus monkeys, respectively. Chronic treatment of everestmab to GK and diet 
      induced obese (DIO) rats achieved beneficial effects on weight reducing, HbA1c 
      lowering, glucose tolerance, liver and pancreas islet function impairment. In 
      summary, everestmab is a unique G-protein-coupled receptor-targeted nanobody 
      fusion protein and exerts potential as a therapeutic treatment for T2DM.
FAU - Pan, Hongchao
AU  - Pan H
AD  - Department of Laboratory Medicine, Shanghai SimpleGene Medical Laboratory, 
      Shanghai, P. R. China.
AD  - Department of Laboratory Medicine, Tongji Hospital of Tongji University, 
      Shanghai, P. R. China.
FAU - Su, Yunnan
AU  - Su Y
AD  - Department of Neurology, Baoshan Branch, Shanghai General Hospital, Shanghai, P. 
      R. China.
FAU - Xie, Yini
AU  - Xie Y
AD  - Department of Laboratory Medicine, The People's Hospital of Jiedong, Jieyang, P. 
      R. China.
FAU - Wang, Weiyong
AU  - Wang W
AD  - Department of Medical Center, Yandong Hospital of Yancheng City, Yancheng, P. R. 
      China.
FAU - Qiu, Wanli
AU  - Qiu W
AD  - Department of Medical Center, Yandong Hospital of Yancheng City, Yancheng, P. R. 
      China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Experimental Medicine Center, The Sixth People's Hospital of 
      Yancheng City, Yancheng, P. R. China.
FAU - Lu, Wenying
AU  - Lu W
AD  - Department of Experimental Medicine Center, The Sixth People's Hospital of 
      Yancheng City, Yancheng, P. R. China.
FAU - Lu, Zhao
AU  - Lu Z
AD  - Department of Laboratory Medicine, Key Laboratory of Pharmaceutical Chemistry, 
      China Pharmaceutical University, NanJing, P. R. China.
FAU - Wang, Weiwei
AU  - Wang W
AD  - Department of Experimental Medicine Center, The Sixth People's Hospital of 
      Yancheng City, Yancheng, P. R. China.
FAU - Shang, Anquan
AU  - Shang A
AD  - Department of Laboratory Medicine, Tongji Hospital of Tongji University, 
      Shanghai, P. R. China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Artif Cells Nanomed Biotechnol
JT  - Artificial cells, nanomedicine, and biotechnology
JID - 101594777
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Single-Domain Antibodies)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/drug therapy
MH  - Glucagon-Like Peptide 1/*genetics
MH  - Glucagon-Like Peptide-1 Receptor/*immunology
MH  - Hypoglycemic Agents/pharmacokinetics/*pharmacology/therapeutic use
MH  - Macaca fascicularis
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Fusion Proteins/pharmacokinetics/*pharmacology/therapeutic use
MH  - Single-Domain Antibodies/*pharmacology/therapeutic use
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Long-acting GLP-1
OT  - anti-diabetic properties
OT  - glucose metabolism
OT  - human serum albumin
OT  - single domain antibody
EDAT- 2020/05/30 06:00
MHDA- 2021/01/09 06:00
CRDT- 2020/05/30 06:00
PHST- 2020/05/30 06:00 [entrez]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/01/09 06:00 [medline]
AID - 10.1080/21691401.2020.1770268 [doi]
PST - ppublish
SO  - Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):854-866. doi: 
      10.1080/21691401.2020.1770268.