2. Academic Validation
  3. Discovery of new benzhydrol biscarbonate esters as potent and selective apoptosis inducers of human melanomas bearing the activated ERK pathway: SAR studies on an ERK MAPK signaling modulator, ACA-28

Discovery of new benzhydrol biscarbonate esters as potent and selective apoptosis inducers of human melanomas bearing the activated ERK pathway: SAR studies on an ERK MAPK signaling modulator, ACA-28

  • Bioorg Chem. 2020 Oct;103:104137. doi: 10.1016/j.bioorg.2020.104137.
Ryosuke Satoh 1,  Naoya Hamada 2,  Ami Yamada 3,  Yuki Kanda 4,  Fumihiro Ishikawa 5,  Teruaki Takasaki 6,  Genzoh Tanabe 7,  Reiko Sugiura 8
Affiliations

Affiliations

  • 1 Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: satohr@phar.kindai.ac.jp.
  • 2 Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: 1933420001u@kindai.ac.jp.
  • 3 Laboratory of Organic Chemistry, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: 1511610091j@kindai.ac.jp.
  • 4 Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: 1745110004k@kindai.ac.jp.
  • 5 Laboratory of Organic Chemistry, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: ishikawa@phar.kindai.ac.jp.
  • 6 Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: takasaki@phar.kindai.ac.jp.
  • 7 Laboratory of Organic Chemistry, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: g-tanabe@phar.kindai.ac.jp.
  • 8 Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan. Electronic address: sugiurar@phar.kindai.ac.jp.
PMID: 32763519 DOI: 10.1016/j.bioorg.2020.104137
Abstract

The recent discovery that an ERK signaling modulator [ACA-28 (2a)] preferentially kills human melanoma cell lines by inducing ERK-dependent Apoptosis has generated significant interest in the field of anti-cancer therapy. In the first SAR study on 2a, here, we successfully developed candidates (2b, 2c) both of which induce more potent and selective Apoptosis towards ERK-active melanoma cells than 2a, thus revealing the structural basis for inducing the ERK-dependent Apoptosis and proposing the therapeutic prospect of these candidates against ERK-dependent cancers represented by melanoma.

Keywords

ACA-28; Anti-melanoma activity; Apoptosis; Benzhydrol derivatives; ERK MAPK; SAR Study.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-147855
    99.76%, ERK MAPK Modulator