NDLI: Ligand-based chemoinformatic discovery of a novel small molecule inhibitor targeting CDC25 dual specificity phosphatases and displaying in vitro efficacy against melanoma cells

Content Provider	PubMed Central
Author	Capasso, Alessandra Cerchia, Carmen Giovanni, Carmen Di Granato, Giuseppina Albano, Francesco Romano, Simona De, Vendittis Emmanuele Ruocco, Maria Rosaria Lavecchia, Antonio
Copyright Year	2015
Abstract	CDC25 phosphatases are important regulators of the cell cycle and represent promising targets for anticancer drug discovery. We recently identified NSC 119915 as a new quinonoid CDC25 inhibitor with potent anticancer activity. In order to discover more active analogs of NSC 119915, we performed a range of ligand-based chemoinformatic methods against the full ZINC drug-like subset and the NCI lead-like set. Nine compounds (3, 5–9, 21, 24, and 25) were identified with K i values for CDC25A, -B and -C ranging from 0.01 to 4.4 μM. One of these analogs, 7, showed a high antiproliferative effect on human melanoma cell lines, A2058 and SAN. Compound 7 arrested melanoma cells in G2/M, causing a reduction of the protein levels of CDC25A and, more consistently, of CDC25C. Furthermore, an intrinsic apoptotic pathway was induced, which was mediated by ROS, because it was reverted in the presence of antioxidant N-acetyl-cysteine (NAC). Finally, 7 decreased the protein levels of phosphorylated Akt and increased those of p53, thus contributing to the regulation of chemosensitivity through the control of downstream Akt pathways in melanoma cells. Taken together, our data emphasize that CDC25 could be considered as a possible oncotarget in melanoma cells and that compound 7 is a small molecule CDC25 inhibitor that merits to be further evaluated as a chemotherapeutic agent for melanoma, likely in combination with other therapeutic compounds.
Ending Page	40222
Starting Page	40202
File Format	PDF
ISSN	19492553
e-ISSN	19492553
Journal	Oncotarget
Issue Number	37
Volume Number	6
Language	English
Publisher	Impact Journals LLC
Publisher Date	2015-10-13
Access Restriction	Open
Rights Holder	Impact Journals LLC
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A Novel, Potent, Small Molecule AKT Inhibitor Exhibits Efficacy against Lung Cancer Cells In Vitro

A Novel, Potent, Small Molecule AKT Inhibitor Exhibits Efficacy against Lung Cancer Cells In Vitro.

Targeting PTPs with small molecule inhibitors in cancer treatment

UNC569, a novel small molecule Mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo

Structure-based discovery of a novel small-molecule inhibitor of TEAD palmitoylation with anticancer activity

A novel selective small-molecule PI3K inhibitor is effective against human multiple myeloma in vitro and in vivo

Dual targeting of MDM2 with a novel small-molecule inhibitor overcomes TRAIL resistance in cancer

KINK-1, a Novel Small-Molecule Inhibitor of IKKβ, and the Susceptibility of Melanoma Cells to Antitumoral Treatment

Ligand-based discovery of a novel GATA2 inhibitor targeting acute myeloid leukemia cells

Ligand-based chemoinformatic discovery of a novel small molecule inhibitor targeting CDC25 dual specificity phosphatases and displaying in vitro efficacy against melanoma cells

Similar Documents

A Novel, Potent, Small Molecule AKT Inhibitor Exhibits Efficacy against Lung Cancer Cells In Vitro

A Novel, Potent, Small Molecule AKT Inhibitor Exhibits Efficacy against Lung Cancer Cells In Vitro.

Targeting PTPs with small molecule inhibitors in cancer treatment

UNC569, a novel small molecule Mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo

Structure-based discovery of a novel small-molecule inhibitor of TEAD palmitoylation with anticancer activity

A novel selective small-molecule PI3K inhibitor is effective against human multiple myeloma in vitro and in vivo

Dual targeting of MDM2 with a novel small-molecule inhibitor overcomes TRAIL resistance in cancer

KINK-1, a Novel Small-Molecule Inhibitor of IKKβ, and the Susceptibility of Melanoma Cells to Antitumoral Treatment

Ligand-based discovery of a novel GATA2 inhibitor targeting acute myeloid leukemia cells

Ligand-based chemoinformatic discovery of a novel small molecule inhibitor targeting CDC25 dual specificity phosphatases and displaying in vitro efficacy against melanoma cells