Stemolecule™ ALK5 Inhibitor

Stemolecule ALK5 Inhibitor, also known as RepSox, E 616452, and SJN 2511, is a selective and ATP-competitive inhibitor of the TGFβ family type I receptor activin receptor-like kinase (ALK5)¹. The ALK5 Inhibitor works by preventing autophosphorylation of ALK5. It has also been shown that ALK5 can replace Sox2 when reprogramming cells to induced pluripotent stem (iPS) cells. Through inhibition of the TGFβ pathway, ALK5 works to reprogram cells that have been transduced with Oct4, Klf4, and c-Myc². ALK5 Inhibitor promotes the differentiation of MYH11-positive cells by modulating NOTCH signaling⁴.

Stemgent and the Stemolecule brand name are trademarks of REPROCELL Inc., Japan.

Product Name: Stemolecule ALK5 Inhibitor (RepSox)

Catalog Number: 04-0015

Size: 1 mg

Alternate Name(s)

• RepSox
• E 616452
• SJN 2511
• 2-(3-(6-methylpyridine-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine

Chemical Formula: C₁₇H₁₃N₅

Molecular Weight: 287.32

CAS Number: 446859-33-2

Purity: Greater than 99% by HPLC analysis

Formulation: Yellow solid

Solubility: For a 10 mM concentrated stock solution of ALK5 Inhibitor, reconstitute the compound by adding 348 µL of DMSO to the entire contents of the vial. If precipitate is observed, warm the solution to 37 °C for 2 to 5 minutes. For cell culture, the media should be prewarmed prior to adding the reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%. This molecule is soluble in DMSO at 100 mM and methanol at 17 mM.

Storage and Stability: Store powder at 4 °C or lower, protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20 °C. The effect of storage of stock solutions should be verified for each application.

Quality Control: The purity of ALK5 Inhibitor was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of ALK5 Inhibitor was tested on HeLa and HEK293 cells.

Specification Sheets:

• 04-0015 Specifications Sheet

Safety Data Sheets:

• 04-0015 Safety Data Sheet

1. Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., Hao, E., Hayek, A., Deng, H., and Ding, S. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4: 16-19 (2009).
2. Gellibert, F., Woolven, J., Fouchet, M. H., Mathews, N., Goodland, H., Lovegrove, V., Laroze, A., Nguyen, V. L., Sautet, S., Wang, R., Janson, C., Smith, W., Krysa, G., Boullay, V., De Gouville, A. C., Huet, S., and Hartley, D. Identification of 1, 5-naphthyridine derivatives as a novel series of potent and selective TGFβ type I receptor inhibitors. J Med Chem 47: 4494-4506 (2004).
3. Ichida, J.K., Blanchard, J., Lam, K., Son, E.Y., Chung, J.E., Egli, D., Loh, K.M., Carter, A.C., Di Giorgio, F.P., Koszka, K., Huangfu, D., Akutsu, H., Liu, D.R., Rubin, L.L., and Eggan, K. A small-molecule inhibitor of Tgf-? signaling replaces Sox2 in reprogramming by inducing Nanog. Cell Stem Cell 5: 491-503 (2009).
4. Zhang J; McIntosh BE; Wang B; Brown E; Probasco MD; Webster S; Duffin B; Zhou Y; Guo L-W; Burlingham WJ; Kent C; Ferris M; Thomson JA. A human pluripotent stem cell-based screen for smooth muscle cell differentiation and maturation identifies inhibitors of intimal hyperplasia. Stem Cell Rep 12: 1269-1281 (2019).

Additional Publications

• Ma S; Viola R: Sui L; Cherubini V; Barbetti F; Eigli D. β Cell Replacement after Gene Editing of a Neonatal Diabetes-Causing Mutation at the Insulin Locus. Stem Cell Reports https://doi.org/10.1016/j.stemcr.2018.11.006: (2018).
• Yang J; Karu K; Edwards JG; Eisenberg CA; Eisenberg LM. Inhibition of Histone Methyltransferase, Histone Deacetylase, and β-Catenin Synergistically Enhance the Cardiac Potential of Bone Marrow Cells. Stem Cells International 2017:3464953 (2017).
• Zhu S; Russ HA; Wang X; Zhang M; Ma T; Xu T; Tang S; Hebrok M; Deng S. Human pancreatic β-like cells converted from fibroblasts. Nature Commun 7:10080 (2016).
• Yang J; Kaur K; Ong LL; Eisenberg CA; Eisenberg LM. Inhibition of G9a histone methyltransferase converts bbone marrow mesenchymal stem cells to cardiac competent progenitors. Stem Cells International Article 270428 (2015). doi:10.1155/2015/270428
• Cho Y; Szabolcs A; Duuta SK; Yaqoob U; Jagavelu K; Leof EB; Urrutia RA; Shah VH; Mukhopadhyay D. Neuropilin-1 mediates divergent R-Smad signaling and the myofibroblast phenotype. J Biol Chem 285:31840 (2010).