DAPT (GSI-IX)
DAPT (CAS 208255-80-5) is an orally bioavailable γ-secretase inhibitor, functioning as a potent and selective blocker of γ-secretase activity in cellular systems and exhibiting inhibitory activity on Notch signaling pathways in diverse cell types. Additionally, it suppresses the proteolytic processing of amyloid precursor protein (APP) and Notch receptor substrates.
In cell-based assays, DAPT reduces the generation of amyloid-β peptides with an IC50 of 115 nM, as well as inhibits total γ-secretase activity with an IC50 of 200 nM, tested against various mammalian cell lines. It can also induce cellular differentiation, modulate downstream signaling cascades, and trigger autophagy and apoptosis depending on experimental conditions.
In basic and translational research applications, DAPT is widely used for the study of neurodegenerative diseases, such as Alzheimer’s disease, autoimmune disorders, lymphoproliferative conditions, and cancer. Furthermore, DAPT enables the dissection of Notch-related signaling mechanisms, providing a tool for evaluating the role of γ-secretase in cellular development, immune regulation, and tumorigenesis. Its application extends to investigations of cell fate determination and neuroprotection, supporting the development of novel therapeutic strategies targeting γ-secretase dependent pathways.
- 1. Hyung Suk Oh, Shu-Fan Chou, et al. "Validation of human sensory neurons derived from inducible pluripotent stem cells as a model for latent infection and reactivation by herpes simplex virus 1." mBio. 2025 Aug 18:e0187125. PMID: 40823836
- 2. SEUNG WOO KANG. "THYMUS: A ROLLER COASTER OF FOXN1." The University of Georgia May 2024
- 3. Julia Sidor, Megan Gillette, et al. "Role of Presenilin-1 in Aggressive Human Melanoma." Int J Mol Sci. 2022 Apr 28;23(9):4904. PMID: 35563300
- 4. Xiaoya An, Guoliang Wang, et al. "Novel cell culture paradigm prolongs mouse corneal epithelial cell proliferative activity in vitro and in vivo." Front Cell Dev Biol. 2021 Jun 30;9:675998. PMID: 34277619
- 5. Shanfeng Sun, Songsong Jiang, et al. "Cholera toxin induces food allergy through Th2 cell differentiation which is unaffected by Jagged2." Life Sci. 2020 Oct 1;263:118514. PMID: 33010283
- 6. Weigang He, Jinxia Sun, et al. "Andrographolide exerts anti‐inflammatory effects in Mycobacterium tuberculosis‐infected macrophages by regulating the Notch1/Akt/NF‐κB axis." J Leukoc Biol. 2020 Dec;108(6):1747-1764. PMID: 32991757
- 7. Shu min Lv, Hongwen Cai, et al. "Thymosin‑β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF‑κB pathway." Int J Mol Med. 2020 Oct;46(4):1347-1358. PMID: 32945357
- 8. Ireland AS, Micinski AM, et al. "MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate." Cancer Cell. 2020 Jul 13;38(1):60-78.e12. PMID: 32473656
- 9. Zhu M, Li Y, et al. "Effects of bisphenol A and its alternative bisphenol F on Notch signaling and intestinal development: A novel signaling by which bisphenols disrupt vertebrate development." Environ Pollut. 2020;263(Pt B):114443. PMID: 32311622
- 10. Zhu M, Niu Y, et al. "Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models." Chem Res Toxicol. 2020;10.1021/acs.chemrestox.9b00528. PMID: 32041402
- 11. Jennifer E. Speer, Yuli Wang, et al. "Evaluation of human primary intestinal monolayers for drug metabolizing capabilities." Journal of Biological Engineering volume 13, Article number: 82 (2019)
- 12. Wu J, Wang X, et al. "Allyl isothiocyanate may reverse the expression of MRP1 in COPD rats via the Notch1 signaling pathway." Arch Pharm Res. 2019 Sep 30. PMID: 31571144
- 13. Speer JE, Gunasekara DB, et al. "Molecular transport through primary human small intestinal monolayers by culture on a collagen scaffold with a gradient of chemical cross-linking." J Biol Eng. 2019 Apr 27;13:36. PMID: 31061676
- 14. Azimi M, Brown NL. "Jagged1 protein processing in the developing mammalian lens." Biol Open. 2019 Mar 26;8(3). pii: bio041095. PMID: 30890522
- 15. Wu F, Wu D, et al. "Generation of hepato-biliary organoids from human induced pluripotent stem cells." J Hepatol. 2019 Jan 7. pii: S0168-8278(19)30002-9. PMID: 30630011
- 16. MXinwei Feng, Junfeng Lu, et al. "Mycobacterium smegmatis Induces Neurite Outgrowth and Differentiation in an Autophagy-Independent Manner in PC12 and C17.2 Cells." Front. Cell. Infect. Microbiol., 19 June 2018.
- 17. Tang J, Zhou H, et al. "Dual-Mode Imaging-Guided Synergistic Chemo- and Magnetohyperthermia Therapy in a Versatile Nanoplatform To Eliminate Cancer Stem Cells." ACS Appl Mater Interfaces.2017 Jul 19;9(28):23497-23507. PMID: 28661121
- 18. Fan Y, Gao X, Chen J, et al. "HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway." J Neurosci. 2016 Nov 2;36(44):11362-11373. PMID: 27807176
- 19. Zhou, Xuanxuan, et al. "Tetrahydroxystilbene glucoside extends mouse lifespan via up-regulating neural Klotho and down-regulating neural insulin/insulin-like growth factor 1." Neurobiology of Aging (2014).
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 432.46 |
| Cas No. | 208255-80-5 |
| Formula | C23H26F2N2O4 |
| Synonyms | LY-374973 |
| Solubility | ≥21.62 mg/mL in DMSO; insoluble in H2O; ≥16.36 mg/mL in EtOH with ultrasonic |
| Chemical Name | tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate |
| SDF | Download SDF |
| Canonical SMILES | C[C@@H](C(N[C@H](C(OC(C)(C)C)=O)c1ccccc1)=O)NC(Cc1cc(F)cc(F)c1)=O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
SHG -44 human glioma cell line |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
5d; 1.0 μM |
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Applications |
Cell viability in each group was detected by MTT. Compared with those in group A (control), proliferation of SHG -44 cells in group B (0.5 μM), C (1μM), D (5 μM) and E (10 μM) were inhibited by DAPT. For group B and A, the results were significantly different (P0.05). It indicated that DAPT is a concentration-dependent inhibitor that may obviously inhibit SHG-44 cells proliferation. As concentration of DAPT higher than 1.0 μmol/L showed no more obvious disparities in cell inhibition, concentration of 1.0 μmol/L was our prioriy. |
| Animal experiment [2]: | |
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Animal models |
Male Balb/C mice |
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Dosage form |
10 mg/kg/day; subcutaneously injected |
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Applications |
CT26 colon adenocarcinoma cells (5 × 105 cells) in 500 μL of Phosphate buffer solution (PBS) were inoculated subcutaneously into the dorsum of all mice. Administration of DAPT significantly reduced serum sVEGFR1, while could not change serum VEGF concentration in control mice. Immunohistochemical study of the tumors showed that CD31 positive cells were reduced after DAPT administration (280.6 ± 81 vs. 386 ± 59.9 CD31 positive cells/mm2), although it was not statistically significant. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Liu X, Xu Q R, Xie W F, et al. DAPT suppresses the proliferation of human glioma cell line SHG-44[J]. Asian Pacific journal of tropical medicine, 2014, 7(7): 552-556. [2] Kalantari E, Saeidi H, Kia N S, et al. Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice[J]. Advanced biomedical research, 2013, 2. |
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| Description | DAPT (GSI-IX) is a novel inhibitor of γ-secretase with IC50 of 20 nM in HEK 293 cells. | |||||
| Targets | Aβ | |||||
| IC50 | 20 nM | |||||
Quality Control & MSDS
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