Pim Kinase Inhibitors

Pim kinases are a family of serine/threonine kinases that play critical roles in regulating cell cycle progression and programmed cell death (apoptosis). Two major isoforms have been identified—Pim-1 and Pim-2—both of which are expressed in lymphoid cells and are essential for cytokine-driven proliferation. While most studies have focused on Pim-1, evidence suggests that both isoforms may contribute to tumor development.

Pim-1 promotes cell cycle advancement by activating the regulator Cdc25, thereby stimulating cell division. This activity can result in uncontrolled cell growth. Genetic variations such as single nucleotide polymorphisms (SNPs) in the Pim-1 gene have been correlated with diffuse large B-cell lymphoma as well as elevated risk for lung cancer. Given its central role in cell division, pharmacological inhibition of Pim-1 has shown therapeutic potential in various malignancies.

Pim Kinase Inhibitors carried by Aladdin:

· AZD-1208 (A127698≥98%,  A420898 10mM in DMSO): A selective Pim-1 inhibitor that triggers cell cycle arrest and apoptosis in leukemia cells. It also reduces phosphorylation of downstream effectors including Bcl-2, 4EBP1, p70S6K, and S6.

· SMI-4a (T125988 ≥98%, S408954 10mM in DMSO): Another Pim-1 inhibitor, SMI-4a suppresses phosphorylation of eIF4B, inhibits tumor proliferation, and induces apoptosis and cell cycle arrest in both myeloid and lymphoid cells.

· MLN-2238 (M128010 ≥98%, I408530 10mM in DMSO): A proteasome inhibitor that downregulates Pim-1 activity in multiple myeloma by modulating tumor suppressor miR-33b expression.

· Mitoxantrone Dihydrochloride (M129460 ≥97%, M408662 10mM in DMSO): A DNA intercalating agent used clinically for multiple sclerosis, lymphomas, and leukemias. Research indicates that part of its antitumor effect may arise from direct inhibition of Pim-1.

References:

1. Bachmann M, Möröy T. Int J Biochem Cell Biol. 2005 Apr;37(4):726-30.

2. Kim DS, Sung JS, Shin ES, et al. Cancer Res Treat. 2008 Dec;40(4):190-6.

3. Keeton EK, McEachern K, Dillman KS, et al. Blood. 2014 Feb 6;123(6):905-13.

4. Yang J, Wang J, Chen K, et al. Cancer Res. 2013 Aug 1;73(15):4898-908.

5. Tian Z, Zhao JJ, Tai YT, et al. Blood. 2012 Nov 8;120(19):3958-67.

6. Wan X, Zhang W, Li L, et al. J Med Chem. 2013 Mar 28;56(6):2619-29.

Aladdin: https://www.aladdinsci.com/