2. Academic Validation
  3. Novel dual LSD1/HDAC6 inhibitors for the treatment of multiple myeloma

Novel dual LSD1/HDAC6 inhibitors for the treatment of multiple myeloma

  • Bioorg Med Chem Lett. 2021 Feb 15;34:127763. doi: 10.1016/j.bmcl.2020.127763.
M Naveen Sadhu 1,  Dhanalakshmi Sivanandhan 1,  Chandru Gajendran 1,  Subramanyam Tantry 2,  Purushottam Dewang 2,  Kannan Murugan 2,  Srinatha Chickamunivenkatappa 2,  Mohd Zainuddin 1,  Sreekala Nair 3,  Krishnakumar Vaithilingam 4,  Sridharan Rajagopal 5
Affiliations

Affiliations

  • 1 Jubilant Therapeutics India Ltd, Bangalore 560022, India.
  • 2 Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
  • 3 Department of Discovery Biology, Jubilant Biosys Ltd, Bangalore 560022, India.
  • 4 Department of Structural Biology, Jubilant Biosys Ltd, Bangalore 560022, India.
  • 5 Jubilant Therapeutics India Ltd, Bangalore 560022, India. Electronic address: [email protected].
PMID: 33359604 DOI: 10.1016/j.bmcl.2020.127763
Abstract

Lysine specific demethylase 1 (LSD1) and HDAC6 are epigenetic proteins associated with several diseases, including Cancer and combined inhibition of these proteins could be highly beneficial in treating some cancers such as AML, MM and solid tumors. Multiple myeloma (MM) is a challenging Cancer with fast relapse rate where novel treatment options are the need of the hour. We have designed and developed novel, LSD1 and HDAC6 selective dual inhibitors to target MM. Our dual inhibitor compound 1 shows superior potency in multiple MM cell lines. In MM.1S xenograft model compound 1 shows superior efficacy compared to single agent LSD1 and HDAC6 inhibitors by oral administration and is well tolerated. Further evaluation of the molecule in other cancers is in progress.

Keywords

Drugs (IMiDs).; Histone deacetylase 6 (HDAC6), Multiple; Lysine-specific demethylase 1 (LSD1); Myeloma (MM), Immunomodulatory imide.

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