DAPT

• CAT Number: A000703
• CAS Number: 208255-80-5
• Molecular Formula: C₂₃H₂₆F₂N₂O₄
• Molecular Weight: 432.46
• Purity: ≥95%
• Synonyms: LY-374973
• Target: Stem Cell/Wnt
• Solubility: >21.6mg/mL in DMSO
• Storage: 3 years -20C powder
• InChI: InChI=1S/C23H26F2N2O4/c1-14(26-19(28)12-15-10-17(24)13-18(25)11-15)21(29)27-20(16-8-6-5-7-9-16)22(30)31-23(2,3)4/h5-11,13-14,20H,12H2,1-4H3,(H,26,28)(H,27,29)/t14-,20-/m0/s1
• InChIKey: DWJXYEABWRJFSP-XOBRGWDASA-N
• SMILES: CC(C(=O)NC(C1=CC=CC=C1)C(=O)OC(C)(C)C)NC(=O)CC2=CC(=CC(=C2)F)F

DAPT, also known GSI-IX, is a potent and selective γ-secretase inhibitor. DAPT is a non-transition-state analogue GSI and is the compound most widely evaluated in experimental models. DAPT causes a reduction in Aβ levels in human primary neuronal cell cultures with IC50 values = 115−200 nM. DAPT blocks Notch signaling in a cell-based assay measuring the activation of the Notch pathway reporter gene with an IC50 = 500 nM. As an inhibitor of Notch, DAPT has also been used in the study of autoimmune and lymphoproliferative diseases.

Reference

1: Panaccione A, Chang MT, Carbone BE, Guo Y, Moskaluk CA, Virk RK, Chiriboga L, Prasad ML, Judson B, Mehra S, Yarbrough WG, Ivanov SV. NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem-Like Cells in Adenoid Cystic Carcinoma. Clin Cancer Res. 2016 Apr 15;22(8):2083-95. doi: 10.1158/1078-0432.CCR-15-2208. PubMed PMID: 27084744.2: Zhou J, Jain S, Azad AK, Xu X, Yu HC, Xu Z, Godbout R, Fu Y. Notch and TGFβ form a positive regulatory loop and regulate EMT in epithelial ovarian cancer cells. Cell Signal. 2016 Apr 10. pii: S0898-6568(16)30076-6. doi: 10.1016/j.cellsig.2016.03.016. [Epub ahead of print] PubMed PMID: 27075926.3: Li P, Lin X, Zhang JR, Li Y, Lu J, Huang FC, Zheng CH, Xie JW, Wang JB, Huang CM. The expression of presenilin 1 enhances carcinogenesis and metastasis in gastric cancer. Oncotarget. 2016 Mar 1;7(9):10650-62. doi: 10.18632/oncotarget.7298. PubMed PMID: 26872378.4: Tang Z, Wei J, Yu Y, Zhang J, Liu L, Tang W, Long J, Zheng X, Jing W. γ-Secretase inhibitor reverts the Notch signaling attenuation of osteogenic differentiation in aged bone marrow mesenchymal stem cells. Cell Biol Int. 2016 Apr;40(4):439-47. doi: 10.1002/cbin.10583. Epub 2016 Feb 4. PubMed PMID: 26801333.5: Campbell DP, Chrysostomou E, Doetzlhofer A. Canonical Notch signaling plays an instructive role in auditory supporting cell development. Sci Rep. 2016 Jan 20;6:19484. doi: 10.1038/srep19484. PubMed PMID: 26786414; PubMed Central PMCID: PMC4726253.6: Qin WD, Zhang F, Qin XJ, Wang J, Meng X, Wang H, Guo HP, Wu QZ, Wu DW, Zhang MX. Notch1 inhibition reduces low shear stress-induced plaque formation. Int J Biochem Cell Biol. 2016 Mar;72:63-72. doi: 10.1016/j.biocel.2016.01.007. Epub 2016 Jan 16. PubMed PMID: 26783939.7: Penazzi L, Tackenberg C, Ghori A, Golovyashkina N, Niewidok B, Selle K, Ballatore C, Smith AB 3rd, Bakota L, Brandt R. Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D. Neuropharmacology. 2016 Jan 6;105:84-95. doi: 10.1016/j.neuropharm.2016.01.002. [Epub ahead of print] PubMed PMID: 26772969.8: Manokawinchoke J, Sumrejkanchanakij P, Subbalekha K, Pavasant P, Osathanon T. Jagged1 inhibits osteoprotegerin expression by human periodontal ligament cells. J Periodontal Res. 2016 Jan 11. doi: 10.1111/jre.12357. [Epub ahead of print] PubMed PMID: 26751719.9: Dinicola S, Pasqualato A, Proietti S, Masiello MG, Palombo A, Coluccia P, Canipari R, Catizone A, Ricci G, Harrath AH, Alwasel SH, Cucina A, Bizzarri M. Paradoxical E-cadherin increase in 5FU-resistant colon cancer is unaffected during mesenchymal-epithelial reversion induced by γ-secretase inhibition. Life Sci. 2016 Jan 15;145:174-83. doi: 10.1016/j.lfs.2015.12.048. Epub 2015 Dec 30. PubMed PMID: 26746659.10: Koistinen NA, Bacanu S, Iverfeldt K. Phosphorylation of Fe65 amyloid precursor protein-binding protein in response to neuronal differentiation. Neurosci Lett. 2016 Feb 2;613:54-9. doi: 10.1016/j.neulet.2015.12.050. Epub 2015 Dec 29. PubMed PMID: 26742640.11: Patel J, Wong HY, Wang W, Alexis J, Shafiee A, Stevenson AJ, Gabrielli B, Fisk NM, Khosrotehrani K. Self-Renewal and High Proliferative Colony Forming Capacity of Late-Outgrowth Endothelial Progenitors is Regulated by Cyclin-Dependent Kinase Inhibitors Driven by Notch Signaling. Stem Cells. 2016 Jan 6. doi: 10.1002/stem.2262. [Epub ahead of print] PubMed PMID: 26732848.12: Li LC, Wang DL, Wu YZ, Nian WQ, Wu ZJ, Li Y, Ma HW, Shao JH. Gastric tumor-initiating CD44(+) cells and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT. Oncol Lett. 2015 Nov;10(5):3293-3299. Epub 2015 Sep 18. PubMed PMID: 26722328; PubMed Central PMCID: PMC4665879.13: Su F, Zhu S, Ruan J, Muftuoglu Y, Zhang L, Yuan Q. Combination therapy of RY10-4 with the γ-secretase inhibitor DAPT shows promise in treating HER2-amplified breast cancer. Oncotarget. 2016 Jan 26;7(4):4142-54. doi: 10.18632/oncotarget.6769. PubMed PMID: 26716652.14: Zhao FL, Qiao PF, Yan N, Gao D, Liu MJ, Yan Y. Hydrogen Sulfide Selectively Inhibits γ-Secretase Activity and Decreases Mitochondrial Aβ Production in Neurons from APP/PS1 Transgenic Mice. Neurochem Res. 2016 May;41(5):1145-1159. Epub 2015 Dec 26. PubMed PMID: 26708452.15: Fei C, Guo J, Zhao Y, Gu S, Zhao S, Li X, Chang C. Notch-Hes pathway mediates the impaired osteogenic differentiation of bone marrow mesenchymal stromal cells from myelodysplastic syndromes patients through the down-regulation of Runx2. Am J Transl Res. 2015 Oct 15;7(10):1939-51. eCollection 2015. PubMed PMID: 26692937; PubMed Central PMCID: PMC4656770.16: Li Z, Wang J, Zhao C, Ren K, Xia Z, Yu H, Jiang K. Acute Blockage of Notch Signaling by DAPT Induces Neuroprotection and Neurogenesis in the Neonatal Rat Brain After Stroke. Transl Stroke Res. 2016 Apr;7(2):132-40. doi: 10.1007/s12975-015-0441-7. Epub 2015 Dec 22. PubMed PMID: 26691164.17: Zhang G, Kang L, Chen J, Xue Y, Yang M, Qin B, Yang L, Zhang J, Lu H, Guan H. CtBP2 Regulates TGFβ2-Induced Epithelial-Mesenchymal Transition Through Notch Signaling Pathway in Lens Epithelial Cells. Curr Eye Res. 2015 Dec 17:1-7. [Epub ahead of print] PubMed PMID: 26681554.18: Zhao J, Liang Y, Song F, Xu S, Nian L, Zhou X, Wang S. TSG attenuates LPC-induced endothelial cells inflammatory damage through notch signaling inhibition. IUBMB Life. 2016 Jan;68(1):37-50. doi: 10.1002/iub.1458. Epub 2015 Dec 10. PubMed PMID: 26662286.19: Bai XC, Rajendra E, Yang G, Shi Y, Scheres SH. Sampling the conformational space of the catalytic subunit of human γ-secretase. Elife. 2015 Dec 1;4. pii: e11182. doi: 10.7554/eLife.11182. PubMed PMID: 26623517; PubMed Central PMCID: PMC4718806.20: Onai T, Aramaki T, Inomata H, Hirai T, Kuratani S. On the origin of vertebrate somites. Zoological Lett. 2015 Nov 26;1:33. doi: 10.1186/s40851-015-0033-0. eCollection 2015. PubMed PMID: 26613046; PubMed Central PMCID: PMC4660845.