A 83-01 (LKT Product: A001001)
A 83-01 is an inhibitor of ALK-5 (activin receptor-like kinase), a member of the TGF-β (transforming growth factor-β) superfamily. Recent work shows importance of this small molecule in the morphogenesis of stem cells. In one study, A-83-01 in conjunction with other small molecules resulted in the development of induced pluripotent stem cells from human urine-derived cells. An additional study used A-83-01 in conjunction with 2 other small molecules to convert mature hepatocytes to chemically induced liver progenitor cells. These novel cells were sustainable and able to be serially passaged.
BAY 80-6946 Hydrochloride (LKT Product: B0397)
BAY 80-6946 (copanlisib) is a PI3Kα (phosphatidylinosital-3-kinase) and PI3Kδ selective inhibitor. In studies looking at the utility of BAY 80-6946 in diffuse large B Cell lymphoma (DLBCL), the compound showed IC50 values for cytotoxicity due to high expression of PI3Kα in this carcinoma. This inhibitor also decreased phosphorylation of Akt. In in vivo mouse xenograft studies, treatment with BAY 80-6946 in conjunction with ibrutinib resulted in cancer remission as a complete response to both kinase inhibitors.
SB 202190 (LKT Product: S041001)
SB 202190 is pyridinyl imidazole inhibitor of p38 MAP kinase. Due to the ubiquitous nature of p38, SB 202190 shows interesting activity in different biochemical systems. One study shows that treatment of HEK 293T cells with SB 202190 resulted in inhibition of the casein kinase 1 (CK1). This was determined with a lack of phosphorylation of CREB. An additional study showed that inhibition of p38 kinase results in the protection of mice infected with H5N1 avian flu. SB 202190 can be used for investigations of other p38 MAP kinase quandries.
Tojo M, Hamashima Y, Hanyu A, Kajimoto T, et al. (2005) “The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β.” Cancer Sci 96(11):791-800. DOI: 10.1111/j.1349-7006.2005.00103.x
Li D, Wang L, Hou J Shen Q et al. (2016) “Optimized Approaches for Generation of Integration-free iPSCs from Human Urine-Derived Cells with Small Molecules and Autologous Feeder.” Stem Cell Reports 6:717-728. DOI: 10.1016/j.stemcr.2016.04.001
Katsuda T, Kawamata M, Hagiwara K, Takahashi R, et al. “Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity” Cell Stem Cell. 20:41-55. DOI: 10.1016/j.stem.2016.10.007
Scott WJ, Hentemann MF, Rowley RB, Bull CO et al. (2016) “Discovery and SAR of Novel 2,3-Dihydroimidazo[1,2-c]-quinazoline PI3K Inhibitors:Identification of Copanlisib (BAY 80-6946).” ChemMedChem 11:1517-1530. DOI:10.1002/cmdc.201600148
Paul J, Soujon M, Wengner AM, Zitzmann-Kolbe S, et al. (2017) “Simultaneous Inhibition of PI3Kδ and PI3Kα Induces ABC-DLBCL Regression by Blocking BCR-Dependent and Independent Activation of NF-κB and AKT.” Cancer Cell 31:64-78. DOI: 10.1016/j.ccell.2016.12.003
Shanware NP, Williams LM, Bowler MJ and Tibbetts RS. (2009) “Non-specific in vivo inhibition of CK1 by the pyridinyl imidazole p38 inhibitors SB 203580 and SB 202190.” BMB Reports 42(3):142-147.
Borgeling Y, Schmolke M, Viemann D, Nordhoff C, Roth J and Ludwig S. (2014). “Inhibition of p38 Mitogen-activated Protein Kinase Impairs Influenza Virus-induced Primary and Secondary Host Gene Responses and Protects Mice from Lethal H5NI Infection.” J Biol Chem 289(1): 13-27. DOI: 10.1074/jbc.M113.469239.