Structure-based design, synthesis, and evaluation of Bcl-2/Mcl-1 dual inhibitors.
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Drug Design
Drug Screening Assays, Antitumor
HEK293 Cells
Humans
Molecular Docking Simulation
Molecular Structure
Myeloid Cell Leukemia Sequence 1 Protein
/ antagonists & inhibitors
Phenalenes
/ chemical synthesis
Proto-Oncogene Proteins c-bcl-2
/ antagonists & inhibitors
Structure-Activity Relationship
Bcl-2/Mcl-1 dual inhibitor
anticancer activities
apoptosis
Journal
Archiv der Pharmazie
ISSN: 1521-4184
Titre abrégé: Arch Pharm (Weinheim)
Pays: Germany
ID NLM: 0330167
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
06
01
2020
revised:
28
02
2020
accepted:
04
03
2020
pubmed:
17
3
2020
medline:
31
12
2020
entrez:
17
3
2020
Statut:
ppublish
Résumé
Based on our previously reported Bcl-2/Mcl-1 dual inhibitor 4-thiomorpholinyl-2-cyano-3-amidinophenalenone (A1) that simultaneously occupies the p2 and p4 hydrophobic pockets of Bcl-2 and Mcl-1, we optimized molecules with different bond angles of the groups extending to the p4 pocket and bulky hydrophobic groups to explore p2. Research on structure-activity relationship resulted in a new derivative B4 that is capable of occupying both the p2 and p4 more deeply and completely than A1, with K
Identifiants
pubmed: 32175625
doi: 10.1002/ardp.202000005
doi:
Substances chimiques
Antineoplastic Agents
0
BCL2 protein, human
0
MCL1 protein, human
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Phenalenes
0
Proto-Oncogene Proteins c-bcl-2
0
phenalen-1-one
548-39-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2000005Subventions
Organisme : National Natural Science Foundation of China
ID : 81430083
Organisme : National Natural Science Foundation of China
ID : 81570129
Organisme : National Natural Science Foundation of China
ID : 81903462
Organisme : China Postdoctoral Science Foundation
ID : 2018M641694
Informations de copyright
© 2020 Deutsche Pharmazeutische Gesellschaft.
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