2-(Hydroxymethyl)-2-(methoxymethyl)quinuclidin-3-one

• CAT Number: R061578
• CAS Number: 5291-32-7
• Molecular Formula: C10H17NO3
• Molecular Weight: 199.3
• Purity: ≥95%
• Synonyms: PRIMA 1Met; APR 246; 2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one
• Target: Autophagy
• Solubility: >10mg/mL in DMSO
• Storage: Store at 4°C
• InChI: InChI=1S/C10H17NO3/c1-14-7-10(6-12)9(13)8-2-4-11(10)5-3-8/h8,12H,2-7H2,1H3
• InChIKey: BGBNULCRKBVAKL-UHFFFAOYSA-N
• SMILES: O=C1C2CCN(CC2)C1(CO)COC

APR-246(cas 5291-32-7), also known as PRIMA-1MET, is a quinuclidinone derivative that targets the Wrap53 gene with potential antineoplastic activity. p53 activator APR-246 binds to and activates transcription of the Wrap53 gene, which results in an increase in WRAP53 p53 antisense transcript levels and, potentially, an increase in native p53 activity; in turn, increased p53 activity may lead to an induction of cell cycle arrest and apoptosis in tumor cells. This agent may work synergistically with other antineoplastic agents.

Reference

1: Shalom-Feuerstein R, Serror L, Aberdam E, Müller FJ, van Bokhoven H, Wiman KG, Zhou H, Aberdam D, Petit I. Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2152-6. doi: 10.1073/pnas.1201753109. Epub 2013 Jan 25. PubMed PMID: 23355677.
2: Shen J, van den Bogaard EH, Kouwenhoven EN, Bykov VJ, Rinne T, Zhang Q, Tjabringa GS, Gilissen C, van Heeringen SJ, Schalkwijk J, van Bokhoven H, Wiman KG, Zhou H. APR-246/PRIMA-1MET rescues epidermal differentiation in skin keratinocytes derived from EEC syndrome patients with p63 mutations. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2157-62. doi: 10.1073/pnas.1201993110. Epub 2013 Jan 25. PubMed PMID: 23355676.
3: Lehmann S, Bykov VJ, Ali D, Andrén O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10. PubMed PMID: 22965953.
4: Zandi R, Selivanova G, Christensen CL, Gerds TA, Willumsen BM, Poulsen HS. PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53. Clin Cancer Res. 2011 May 1;17(9):2830-41. doi: 10.1158/1078-0432.CCR-10-3168. Epub 2011 Mar 17. PubMed PMID: 21415220.
5: Bao W, Chen M, Zhao X, Kumar R, Spinnler C, Thullberg M, Issaeva N, Selivanova G, Strömblad S. PRIMA-1Met/APR-246 induces wild-type p53-dependent suppression of malignant melanoma tumor growth in 3D culture and in vivo. Cell Cycle. 2011 Jan 15;10(2):301-7. Epub 2011 Jan 15. PubMed PMID: 21239882.
6: Ali D, Jönsson-Videsäter K, Deneberg S, Bengtzén S, Nahi H, Paul C, Lehmann S. APR-246 exhibits anti-leukemic activity and synergism with conventional chemotherapeutic drugs in acute myeloid leukemia cells. Eur J Haematol. 2011 Mar;86(3):206-15. doi: 10.1111/j.1600-0609.2010.01557.x. Epub 2011 Jan 11. PubMed PMID: 21114538.
7: Rökaeus N, Shen J, Eckhardt I, Bykov VJ, Wiman KG, Wilhelm MT. PRIMA-1(MET)/APR-246 targets mutant forms of p53 family members p63 and p73. Oncogene. 2010 Dec 9;29(49):6442-51. doi: 10.1038/onc.2010.382. Epub 2010 Sep 6. PubMed PMID: 20818419.