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Updated: Feb 15, 2026

NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases
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Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity

Shiro Fujii1, Shingen Nakamura1, Asuka Oda1

  • 1Department of Haematology, Endocrinology and Metabolism, Tokushima University Graduate School, Tokushima, Japan.

British Journal of Haematology
|January 13, 2018
PubMed

Insights

New PIM2 inhibitors, SMI-16a and SMI-4a, show unique efficacy against multiple myeloma (MM) by reducing PIM2 protein levels, especially in acidic environments. These compounds also enhance proteasome inhibitor effectiveness in MM treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Proviral Integrations of Moloney virus 2 (PIM2) is overexpressed in multiple myeloma (MM) cells, presenting a key therapeutic target.
  • Existing PIM inhibitors have varying efficacies and mechanisms against MM.

Purpose of the Study:

  • To validate the therapeutic efficacy of different PIM inhibitors against MM cells.
  • To explore novel therapeutic strategies targeting PIM2 in MM.

Main Methods:

  • Screening of various PIM inhibitors, including thiazolidine-2,4-dione compounds (SMI-16a, SMI-4a) and others (AZD1208, CX-6258, PIM447).
  • Assessment of PIM2 protein levels, MM cell survival, drug efflux function, and clonogenic capacity.
  • Evaluation of drug combinations with proteasome inhibitors (bortezomib, carfilzomib).

Main Results:

  • SMI-16a and SMI-4a reduced PIM2 protein levels and impaired MM cell survival, particularly in acidic conditions.
  • SMI-16a suppressed breast cancer resistance protein efflux, reduced side populations, and inhibited in vitro/in vivo tumorigenicity.
  • SMI-16a mitigated PIM2 protein increase induced by proteasome inhibitors and showed synergistic anti-MM effects with carfilzomib.

Conclusions:

  • Thiazolidine-2,4-dione compounds SMI-16a and SMI-4a uniquely reduce PIM2 protein in MM cells, contributing to their efficacy.
  • The combination of SMI-16a with proteasome inhibitors offers a promising therapeutic strategy for multiple myeloma.
Keywords:
4-dione compoundsPIM2breast cancer resistance proteinmultiple myelomaproteasome inhibitorthiazolidine-2

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