Harman Patil (Editor)

Dinaciclib

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Legal status
  
Investigational

CAS Number
  
779353-01-4

IUPHAR/BPS
  
7379

Synonyms
  
SCH-727965

PubChem CID
  
46926350

ChemSpider
  
25027387

Dinaciclib

Dinaciclib (SCH-727965) is an experimental drug that inhibits cyclin-dependent kinases (CDKs). It is being evaluated in clinical trials for various cancer indications.

Contents

Dinaciclib is being developed by Merck & Co. It was granted orphan drug status by the FDA in 2011.

Mechanisms of action

  • Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains.
  • Dinaciclib (SCH727665) inhibits the unfolded protein response (UPR) through a CDK1 and CDK5-dependent mechanism.

    • Anti-tumoral action

  • In melanoma
  • The anti-melanoma activity of dinaciclib is dependent on p53 signaling.
  • In chronic lymphocytic leukemia (CLL)
  • Dinaciclib promotes apoptosis and abrogates microenvironmental cytokine protection in chronic lymphocytic leukemia cells.
  • In pancreatic cancer
  • Dinaciclib inhibits pancreatic cancer growth and progression in murine xenograft models.
  • In osteosarcoma
  • Dinacliclib induces the apoptosis of osteosarcoma cells.
  • Apoptosis of osteosarcoma cultures can be induced by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor.

    • Clinical trials

  • Phase II
  • Advanced breast cancer
  • Non-small cell lung cancer (NSCLC)
  • Multiple myeloma
  • Advanced melanoma
  • Phase III
  • A comparison of dinaciclib and ofatumumab for treatment of CLL

    • References

    Dinaciclib Wikipedia
    (Text) CC BY-SA