Evidence map›Paper›PMID 34944600›Full record

ArticleBiomedicines2021

Generation of a Novel High-Affinity Antibody Binding to PCSK9 Catalytic Domain with Slow Dissociation Rate by CDR-Grafting, Alanine Scanning and Saturated Site-Directed Mutagenesis for Favorably Treating Hypercholesterolemia.

Zhengli Bai, Menglong Xu, Ying Mei, Tuo Hu, Panpan Zhang, Manman Chen, Wenxiu Lv, Chenchen Lu, Shuhua Tan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Zhengli BaiJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.ORCID 0000-0002-3575-1352
Menglong XuJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Ying MeiJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Tuo HuJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Panpan ZhangJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Manman ChenJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Wenxiu LvJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Chenchen LuJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Shuhua TanJiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.ORCID 0000-0002-4992-8876
China Pharmaceutical University · CN

Funding

China Pharmaceutical University "Double First-Class" project CPU2018GY15National Fund for Fostering Talents of Basic Science 3050040016National Fund for Major Projects of China 2009ZX09103-653National Fund for Major Projects of China 2013ZX09301303-006National Fund for Major Projects of China 2018ZX09301035The Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) none
6 · The paper itself

Abstract

Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has become an attractive therapeutic strategy for lowering low-density lipoprotein cholesterol (LDL-C). In this study, a novel high affinity humanized IgG1 mAb (named h5E12-L230G) targeting the catalytic domain of human PCSK9 (hPCSK9) was generated by using CDR-grafting, alanine-scanning mutagenesis, and saturated site-directed mutagenesis. The heavy-chain constant region of h5E12-L230G was modified to eliminate the cytotoxic effector functions and mitigate the heterogeneity. The biolayer interferometry (BLI) binding assay and molecular docking study revealed that h5E12-L230G binds to the catalytic domain of hPCSK9 with nanomolar affinity (

Indexed as

alanine scanningcatalytic domainmolecular dockingPCSK9saturated site-directed mutagenesissingle-chain variable fragment (scFv)slow dissociation rate

Identifiers

PMID34944600
PMCPMC8698692
OpenAlexW3217453387

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.