Stemolecule™ Purmorphamine

Purmorphamine is a small molecule that promotes the differentiation of human and murine mesenchymal progenitor cells into osteoblasts^1,2. The mechanism of action study of Purmorphamine indicates that it is an agonist of Smoothened, a 7-transmembrane receptor of the hedgehog signaling pathway^3,4. Purmorphamine can also be used to replace sonic hedgehog for the generation of motor neurons from human embryonic stem cells⁵.

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

Product Name: Stemolecule Purmorphamine

Catalog Number: 04-0009

Size: 5 mg

Alternate Name(s): 2-(1-Naphthoxy)-6-(4-morpholinoanilino)- 9-cyclohexylpurine

Chemical Formula: C₃₁H₃₂N₆O₂

Molecular Weight: 520.6

CAS Number: 483367-10-8

Purity: Greater than 96 % by HPLC analysis

Formulation: Pale beige solid

Solubility: For a 10 mM concentrated stock solution of Purmorphamine, reconstitute the compound by adding 960.4 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 use in cell culture, warm the medium just prior to adding the reconstituted compound. Once the compound is added, mix and filter-sterilize the medium using a 0.2 uM low-protein binding filter. Purmorphamine is soluble in DMSO at 50 mM.

Storage and Stability: Store powder at 4 °C 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, protected from light. The effect of storage of stock solutions should be verified for each application.

Quality Control: The purity of Purmorphamine was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. No acute cytotoxicity was observed in mouse embryonic stem cells following a 6 hour exposure to 1 nM — 100 uM of Purmorphamine.

Specification Sheets:

• 04-0009 Specifications Sheet

Safety Data Sheets:

• 04-0009 Safety Data Sheet

1. Wu, X., Ding, S., Ding, Q., Gray, N.S., and Shultz, P.G. A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells. J Am Chem Soc 124: 14520-14521 (2002).
2. Beloti, M.M., Bellesini, L.S., and Rosa, A.L. Puromorphamine enhances osteogenic activity of human osteoblasts derived from bone marrow mesenchymal cells. Cell Biol Int 29: 537-541 (2005).
3. Wu, X., Walker, J., Zhang, J., Ding, S., and Schultz, P.G. Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway. Chem Biol 11: 1229-1238 (2004).
4. Sinha, S., and Chen, J.K. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat Chem Biol 2: 29-30 (2006).
5. Li, X.J., Hu, B.Y., Jones, S.A., Zhang, Y.S., Lavaute, T., Du, Z.W., and Zhang, S.C. Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules. Stem Cells 26: 886-893 (2008).

Additional Publications

• Ustyantseva E; Pavlova SV; Malakhova AA; Ustyantsev K; Zakian SM; Medvedev SP. Oxidative stress monitoring in iPSC-derived motor neurons using genetically encoded biosensors of H₂O₂. Sci Rep 12:8928 (2022).
• Li H; Jiang H; Li L; Yan Z; Feng J. Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells. Molec Phychiatry 44682:DOI: 10.1038/s41380-022-01628-1 (2022).
• Wang T; Liu H; Itoh K; Oh S; Zhao L ;Murata D; Sesaki H; Hartung T; Na CH; Wang J. C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly. Cell Metabolism 33:531-546.e9 (2021).
• Seo BA; Kim D; Hwang H; Kim MS; Ma S-H; Kweon SH; Wang J; Yoo JM; Choi S; Kwon SH; Kange S-U; Kam T-I; Kim K; Karuppagounder SS; Kang BG; Lee S; Park H; Kim S; Yan W; Li YS; Kuo SH; Redding-Ochoa J; Pletnikova O; Troncosco JC; Lee G' Mao X; Dawson VL; Dawson TM; Ko HS. TRIP12 ubiquitination of glucocerebrosidase contributes to neurodegeneration in Parkinson’s disease. Neuron 23:3753-74.e11 (2021).
• Akhshi T. Non-Canonical Hedgehog Activity Initiates Ciliogenesis via LKB1-AMPK and Gα_i-LGN-NuMA-Dynein Axes. Ph.D. Thesis, Univ of Toronto : (2020).
• Fernandes HJR; Patikas M; Foskolou S; Field SF; Park J-E; Myrne ML; Bassett AR; Metzakopian E. Single-Cell Transcriptomics of Parkinson’s Disease Human In Vitro Models Reveals Dopamine Neuron-Specific Stress Responses. Cell Reports 33:108263 (2020).
• von Troyer M. Establishment of an alginate based 3D culture system for the generation of dopaminergic neurons. Masters Thesis, Univ Innsbruck : (2020).
• Ahfeldt T; Ordureau A; Bell C; Sarrafha L; Sun C; Piccinotti S; Crass T; Parfitt GM; Paulo JA; Yanagawa J; Uozumi T; Kiyota Y; Harper JW' Rubin LL. Pathogenic Pathways in Early-Onset Autosomal Recessive Parkinson's Disease Discovered Using Isogenic Human Dopaminergic Neurons. Stem Cell Rep in press:doi.org/10.1016/j.scemcr.2019.12.005 (2020).
• Mahajani S; Raina A; Fokken C; Kügler S; Bähr M. Homogenous generation of dopaminergic neurons from multiple hiPSC lines by transient expression of transcription factors. Cell Death Disease 10:898 (2019).
• Gantner CWB. Investigating Brain Repair and Development Using Stem Cells. Ph. D. Thesis, University of Melbourne : (2019).
• Koutmani Y; Gampierakis IA; Polissidis A; Ximerakis M: Koutsoudaki PN; Polyzos A; Agrogiannis G; Karaliota S; Thomaidou D; Rubin LL; Politis PK; Karakis KP. CRH Promotes the Neurogenic Activity of Neural Stem Cells in the Adult Hippocampus. Stem Cell Rep 28:932-945.e7 (2019).
• van Rhijn, J-R. The role of FOXP2 in striatal circuitry. Ph.D. Thesis, Radboud University Nijmegen : (2019).
• Adkar SS; Wu C-L; WIllard VP; Dicks A; Ettyreddy A; Steward N; Bhutani N; Gersbach CA; Guilak F. Step‐Wise Chondrogenesis of Human Induced Pluripotent Stem Cells and Purification Via a Reporter Allele Generated by CRISPR‐Cas9 Genome Editing. Stem Cells 37:65-76 (2019).
• Sun X; Song J; Huang H; Chen H; Qian K. Modeling hallmark pathology using motor neurons derived from the family and sporadic amyotrophic lateral sclerosis patient-specific iPS cells. Stem Cell Res Therapy 9:315 (2018).
• Chen Z;l Ren X; Xu X; Zhang Z; Hui Y; Liu Z; Shi L; Fang Y; Ma L; Liu T; Terheyden-Keighley D; Liu L; Zhang X. Genetic Engineering of Human Embryonic Stem Cells for Precise Cell Fate Tracing during Human Lineage Development. Stem Cell Rep in press:https://doi.org/10.1016/j.stemcr.2018.09.014 (2018).
• Xia N; Zhang P; Fang F; Wang Z; Rothstein M; Agulo B; Chiang R; Taylor J; Reijo Pera RA. Transcriptional comparison of human induced and primary midbrain dopaminergic neurons. Scientific Reports6:20270. doi:10.1038/srep20270 (2016).
• Carballo-Molina OA; Sánchez-Navarro A; López-Ornelas A; Lara-Rodarte R; Salazar P; Campos-Romo A; Ramos-Meija V; Velasco I. Semaphorin 3C Released from a Biocompatible Hydrogel Guides and Promotes Axonal Growth of Rodent and Human Dopaminergic Neurons. Tissue Eng Part A 22:850-861 (2016).
• Titmarsh DM; Glass NR; Mills RJ; Hidalgo A; Volvetang EJ; Porrello ER; Hudson JE; Cooper-White JJ. Induction of human iPSC-derived cardiomyocyte proliferation revealed by combinatorial screening in high density microbioreactor arrays. Sci Rep 6:24637 (2016).
• Grow DA; Simmons DV; Gomez JA; Wanat MH; McCarrey JR; Paladini CA; Navara CS. Differentiation and characterizaton of dopaminergic neurons from baboon induced pluripotent stem cells. Stem Cells Transl Med 5:1133-44 (2016).
• Zimmerlan L; Park TS; Huo JS; Verma K; Pather SR; Talbot CC; Agarwal J; Steppan D; Zhang YW; Considine M; Guo H; Zhong X; Gutierrez C; Cope L; Canto-Soler MV; Friedman AD; Baylin SB; Zambdis ET. Tankyrase inhibition promotes a stable human naive pluripotent state with improved functionality. Development 2016:dev.138982 (2016).
• Fonoudi H; Ansari H; Abbasalizadeh S; Laruani MR; Kiani S; Hashemizadeh S; Zarchi AS; Bosman A; Blue GM; Pahlavan S; Perry M; Orr Y; Mayorchak Y; Vandenberg J; Talkhabi M; Winlaw SD; Harvey RP; Aghdami N; Baharvand H. A universal and robust integrated platform for the scalable production of human cardiomyocytes from pluripotent stem cells. Stem Cells Trans Med 4:1482 (2015).