A83-01

A 83-01 is a selective inhibitor of activin receptor-like kinase (ALK), including the transforming growth factor-β (TGFβ) type I receptor ALK5, the Activin/Nodal receptor ALK4, and the type 1 nodal receptor ALK7¹. This molecule is more potent than SB431542 in its inhibition of ALK4, 5, and 7, and only weakly inhibits ALK1, 2, 3, and 6. A83-01 inhibits the TGFβ-induced epithelial-to-mesenchymal transition (EMT) via the inhibition of Smad2 phosphorylation².

A 83-01 facilitates the conversion of epiblast stem cells to the naїve pluripotent state². and in combination with PD0325901, A83-01 enables OCT4-mediated reprogramming³.

Alternative names: Activin/NODAL/TGFβ pathway inhibitor
Applications: Pluripotent Stem Cells; reprogramming, differentiation
Cell types: Pluripotent Stem Cells, iPSCs, ESCs, hematopoietic stem and progenitor cells

Features & Benefits

• More potent ALK 5 inhibitor than SB431542
• Enables OCT4-mediated reprogramming in combination with PD02158901
• Inhibits specification to mesoderm and endoderm

Preparation & Reconstitution

1. From the lyophilized compound, prepare a concentrated stock solution using the appropriate solvent (DMSO), according to the solubility table or custom calculations.
   
   Example: To generate a 5 mM concentrated stock solution of A 83-01, add 2.37 mL of DMSO to 5 mg of A 83-01.
2. Ensure the compound is completely dissolved in the solvent. This may require gentle warming and/or vortexing/sonication to fully reconstitute the compound.
3. Aliquot the concentrated stock solution in single-use volumes, and either use immediately or freeze at -20°C or -80°C for later use. Avoid freeze/thaw cycles.
4. Concentrated stock solutions are designed to be diluted just prior to use (e.g. 1:1000 dilution in cell culture medium). For use in cell culture, warm the medium just prior to adding the reconstituted compound.

Fun Fact: A83-01 is a highly selective "brake" for specific cell-signaling pathways (ALK4, ALK5, ALK7) that drive unwanted cell changes or spontaneously differentiating, making A83-01 super useful for stabilizing pluripotent stem cells and helping scientists grow more stem cells (clonal expansion).

Keywords: A83-01; TGFβ receptor; TGFβ inhibitor; transforming growth factor beta receptor; Smad; ALK5; ALK4; ALK7; reprogramming; naïve stem cell; epithelial-to-mesenchymal transition; EMT; nodal; pluripotent stem cells

Documents

• Brochure: Small Molecules for Stem Cell Research
• FAQs: General Guide for Small Molecules

References and Publications

1. Fleischauer J, Bastone AL, Selich A, John-Neek P, Weisskoeppel L, Schaudien D, Schambach A, Rothe M. TGFβ Inhibitor A83-01 Enhances Murine HSPC Expansion for Gene Therapy. Cells. 2023 Jul 31;12(15):1978. doi: 10.3390/cells12151978. PMID: 37566057; PMCID: PMC10416825.
2. Tojo, M., et al. The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factorβ. Cancer Sci 96: 791-800 (2005).
3. Li, W., et al. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4: 16-19 (2009).
4. Zhou et al. Conversion of mouse epiblast stem cells to an earlier pluripotency state by small molecules. J Bio Chem 285(39); 29676-80 (2010).
5. Zhu et al., Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7(6): 651-5 (2010).
6. Zhang et al. Pharmacological reprogramming of fibroblasts into neural stem cells by signaling-directed transcriptional activation. Cell Stem Cell 18(5): 653-67 (2016).
7. Taniguchi Y, et al. Enhanced antitumor efficacy of folate-linked liposomal Adriamycin with TGF-β type I receptor inhibitor. Cancer Sci. 2010 Oct;101(10):2207-13.