Person:
Kalin, Jay

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Kalin

First Name

Jay

Name

Kalin, Jay

Filters

20181

Settings

Author's Publications: search.filters.isAuthorOfPublication.45bdc704-9250-42b9-b74b-5b1bd4588630

Search Results

Now showing 1 - 1 of 1
  • Thumbnail Image
    Publication
    Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors
    (Nature Publishing Group UK, 2018) Kalin, Jay; Wu, Muzhou; Gomez, Andrea V.; Song, Yun; Das, Jayanta; Hayward, Dawn; Adejola, Nkosi; Wu, Mingxuan; Panova, Izabela; Chung, Hye Jin; Kim, Edward; Roberts, Holly J.; Roberts, Justin M.; Prusevich, Polina; Jeliazkov, Jeliazko R.; Roy Burman, Shourya S.; Fairall, Louise; Milano, Charles; Eroglu, Abdulkerim; Proby, Charlotte M.; Dinkova-Kostova, Albena T.; Hancock, Wayne W.; Gray, Jeffrey J.; Bradner, James E.; Valente, Sergio; Mai, Antonello; Anders, Nicole M.; Rudek, Michelle A.; Hu, Yong; Ryu, Byungwoo; Schwabe, John W. R.; Mattevi, Andrea; Alani, Rhoda M.; Cole, Philip
    Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes. CoREST knockdown, gene expression, and ChIP studies suggest that corin’s favorable pharmacologic effects may rely on an intact CoREST complex. Corin was also effective in slowing tumor growth in a melanoma mouse xenograft model. These studies highlight the promise of a new class of two-pronged hybrid agents that may show preferential targeting of particular epigenetic regulatory complexes and offer unique therapeutic opportunities.