Stemolecule™ Valproic Acid

Stemolecule Valproic Acid (VPA) is a cell-permeable, small molecule that has been shown to affect several pathways. VPA is a histone deacetylase (HDAC) inhibitor which improves reprogramming efficiency by at least 100 fold¹. VPA also has been found to affect both the Extracellular Signal-Regulated Kinase (ERK), Protein Kinase C (PKC), and the Wnt/β-Catenin pathways. VPA has been reported to regulate the differentiation and proliferation of various cells, including mesenchymal and hematopoietic stem cells, neuroblastoma cells, primary neurons and neural progenitor cells (NPCs)². In the case of hepatic differentiation of mouse embryonic stem cells, Valproic Acid in combination with cytokines differentiate cells into a uniform and homogeneous cell population of hepatic progenitor cells followed by maturation into functional hepatocytes³.

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

Product Name: Stemolecule Valproic Acid

Catalog Number: 04-0007

Size: 5 g

AlternateName(s)

• Sodium 2-propylpentanoate
• Sodium valproate

Chemical Formula: C₈H₁₅O₂·Na

Molecular Weight: 166.2

CAS Number: 1069-66-5

Purity: Greater than 98 % by gas chromatography

Formulation: White crystalline solid

Solubility: This molecule is reported to be soluble in DMSO at 100 mM and water at 300 mM.

Reconstitution: For a 10 mM stock solution of Valproic Acid, add 3.01 mL DMSO to 5 mg of the compound. 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 VPA.

Storage and Stability: Store powder at 4 °C protected from light. Following reconstitution, store aliquots at −20 °C. Stock solutions are stable for 6 months when stored as directed.

Quality Control: The purity of VPA was determined by gas chromatography. The accurate mass was determined by mass spectrometry. Cellular toxicity of VPA was tested on mouse embryonic stem cells.

Specification Sheets:

• 04-0007 Specifications Sheet

Safety Data Sheets:

• 04-0007 Safety Data Sheet

1. Bug, G., Gül, H., Schwarz, K., Pfeifer, H., Kampfmann, M., Zheng, X., Beissert, T., Boehrer, S., Hoelzer, D., Ottmann, O.G., Ruthardt, M. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Res 65: 2537-41 (2005).
2. Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A., and Melton, D. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26: 795-797(2009).
3. Jung, G., Yoon, J., Moon, B., Yang, D., Kim, H., Lee, S., Bryja, V., Arenas, E., and Choi, K. Valproic acid induces differentiation and inhibition of proliferation in neural progenitor cells via the β-catenin-Ras-ERK-p21^Cip/WAFI pathway. BMC Cell Biology 9: 6611-6612(2008).
4. Dong, X., Zhang, G., Zhou, Q., Pan, R., Chen, Y., Xizng, L., and Shao, J. Direct hepatic differentiation of mouse embryonic stem cells induced by valproic acid and cytokines. World J of Gastroenterology 15: 5165-5175 (2009).

Additional Publications

• Sasamoto Y; Hayashi R; Park S-J; Saito-Adachhi M; Suzuki Y; Kawasaki S; Quantock AJ; Nakai K; Tsujikawa M; Nishida K. PAX6 isoforms, along with reprogramming factors, differentially regulate the induction of cornea-specific genes. Scientific Reports 6:20807 (2016).
• Bhutani K; Nazor KL; Williams R; Tran H; Dai H; Dzakula ZZ; Cho EH; Pang AWC; Roa M; Cao H; Schorck NJ; Loring JF. Whole-genome mutational burden analysis of three pluripotency induction methods. Nature Commun 7:10536 (2016)
• Han Y-C, Lim Y; Duffieldl MD; Liu J; Manaph NPA; Yang M; Keating DJ; Zhou X-F. Direct reprogramming of mouse fibroblasts to neural stem cells by small molecules. Stem Cells International 2016:4304916 (2016).
• Wang J; Huang V; Ye L; Barcena A; Lin G; Lue TF; Li L-C. Identification of small activating RNAs that enhance endogenous OCT4 expression in human mesenchymal stem cells. Stem Cells Develop 24:345 (2015).
• Wang, Y-C., Nakagawa, M., Garitaonandia, I., Slavin, I., Altun, G., Lacharite, R. M., Nazor, K. L., Tran, H. T., Lynch, C., L., Leonardo, T. R., Liu, Y., Peterson, S. E., Laurent, L., C., Yamanaka, S., Loring, J. F. Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis. Cell Res 21(11): 1551 - 1563(2011).