Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity was written by Fujii, Shiro;Nakamura, Shingen;Oda, Asuka;Miki, Hirokazu;Tenshin, Hirofumi;Teramachi, Jumpei;Hiasa, Masahiro;Bat-Erdene, Ariunzaya;Maeda, Yusaku;Oura, Masahiro;Takahashi, Mamiko;Iwasa, Masami;Endo, Itsuro;Yoshida, Sumiko;Aihara, Ken-ichi;Kurahashi, Kiyoe;Harada, Takeshi;Kagawa, Kumiko;Nakao, Michiyasu;Sano, Shigeki;Abe, Masahiro. And the article was included in British Journal of Haematology in 2018.Formula: C13H13NO3S This article mentions the following:
Proviral integrations of Moloney virus 2 (PIM2) is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clin. application. Intriguingly, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX-6258, and PIM447. SMI-16a also suppressed the drug efflux function of breast cancer resistance protein, minimized the sizes of side populations and reduced in vitro colony-forming capacity and in vivo tumorigenic activity in MM cells, suggesting impairment of their clonogenic capacity. PIM2 is known to be subject to ubiquitination-independent proteasomal degradation Consistent with this, the proteasome inhibitors bortezomib and carfilzomib increased PIM2 protein levels in MM cells without affecting its mRNA levels. However, SMI-16a mitigated the PIM2 protein increase and cooperatively enhanced anti-MM effects in combination with carfilzomib. Collectively, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a uniquely reduce PIM2 protein in MM cells, which may contribute to their profound efficacy in addition to their immediate kinase inhibition. Their combination with proteasome inhibitors is envisioned. In the experiment, the researchers used many compounds, for example, 5-(4-propoxybenzylidene)thiazolidine-2,4-dione (cas: 587852-28-6Formula: C13H13NO3S).
5-(4-propoxybenzylidene)thiazolidine-2,4-dione (cas: 587852-28-6) belongs to thiazolidine derivatives. Thiazolidine is an important scaffold and has a wide range of promising biological activities. Thiazolidine derivatives have reported anti-inflammatory and anti-nociceptive activity. Thiazolidines unsubstituted on the nitrogen atom are readily hydrolyzed by boiling aqueous solutions of acids or bases and the dissociation is complete in the presence of a compound reacting with one of the cleavage products.Formula: C13H13NO3S
Referemce:
Thiazolidine – Wikipedia,
Thiazolidine – ScienceDirect.com