TAPI-1
TAPI-1 is an inhibitor of tumour necrosis factor with IC50 value of 8.09 μM [1].
TAPI-1 is an inhibitor of TACE/ADAM17 which catalyzes the cleavage of full-length APP to the soluble N-terminal fragment (sAPPα). The release of sAPPα has been reported to be a receptor-coupled process increased by the stimulation of muscarinic receptors. In HEK293 cells, treatment of TAPI-1 resulted in an inhibition of increased sAPPα which was induced by the expressing of M3 subtype. The IC50 values of TAPI-1 in the inhibition of M3-increased sAPPα and constitutive release of sAPPα were 3.61 μM and 8.09 μM, respectively. Besides APP, TAPI-1 was also found to have inhibitory effects on the release of TNF-α, IL6R, TNFRI and TNFRII with IC50 values of 50-100, 5-10, 5-10 and 25-50 mM, respectively [1, 2].
References:
[1] Slack B, Ma L, Seah C. Constitutive shedding of the amyloid precursor protein ectodomain is up-regulated by tumour necrosis factor-α converting enzyme. Biochem. J, 2001, 357: 787-794.
[2] Hooper N, Karran E, Turner A. Membrane protein secretases. Biochem. J, 1997, 321: 265-279.
- 1. Ryosuke Fukuda, Shiori Beppu, et al. "Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells." iScience. 2025 Jan 22;28(2):111872 PMID: 39991543
- 2. Erin Gibbons, Manisha Taya, et al. "GPNMB promotes tumor growth and is a biomarker for lymphangioleiomyomatosis." Endocr Relat Cancer. 2024 May 9;31(6):e230312. PMID: 38614127
- 3. Erin Gibbons, Manisha Taya, et al. "Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis." Endocrine-Related Cancer Volume 31: Issue 6 PMID: 38549521
- 4. Yi Zhang, Feifei Luo, et al. "Soluble NKG2D Ligands Impair CD8+ T Cell Anti-Tumor Function Dependent Of NKG2D Downregulation In The Neuroblastoma." Research Square. February 25th, 2022.
- 5. Zhang Y, Wang Y, et al. "Angiotensin Ⅱ deteriorates advanced atherosclerosis by promoting MerTK cleavage and impairing efferocytosis through AT1R/ROS/p38MAPK/ADAM17 pathway." Am J Physiol Cell Physiol. 2019 Aug 7. PMID: 31390228
- 6. Zhou J, Sun J, et al. "MicroRNA-145 overexpression attenuates apoptosis and increases matrix synthesis in nucleus pulposus cells." Life Sci. 2019 Mar 15;221:274-283. PMID: 30797016
- 7. Ellis-Connell AL, Balgeman AJ, et al. "ALT-803 transiently reduces SIV replication in the absence of antiretroviral treatment." J Virol. 2017 Nov 8. pii: JVI.01748-17. PMID: 29118125
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 499.6 |
| Cas No. | 171235-71-5 |
| Formula | C26H37N5O5 |
| Solubility | ≥24.98 mg/mL in DMSO; ≥15.77 mg/mL in EtOH with ultrasonic; ≥18.1 mg/mL in H2O |
| Chemical Name | N1-((R)-1-(((R)-1-((2-aminoethyl)amino)-1-oxopropan-2-yl)amino)-3-(naphthalen-2-yl)-1-oxopropan-2-yl)-N4-hydroxy-2-isobutylsuccinamide |
| SDF | Download SDF |
| Canonical SMILES | NCCNC([C@@H](C)NC([C@H](NC(C(CC(C)C)CC(NO)=O)=O)CC1=CC2=CC=CC=C2C=C1)=O)=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: | |
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Cell lines |
human pulmonary mucoepidermoid carcinoma cell line, NCI-H292 cells |
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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 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
30 min, 30 μM [1] |
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Applications |
TAPI-1, tumor necrosis factor ɑ protease inhibitor-1, is an inhibitor of TACE (TNF-α converting enzyme). TAPI-1 inhibits ectodomain shedding of TNF-ɑ, L-selectin, and p55 TNF-ɑ receptor. Pretreating cells with TAPI-1 inhibits PMA-induced EGFR phosphorylation. Besides, TAPI-1 could block TGF-ɑ release and block the production of mucin induced by PMA, PA sup, and LPS [1]. TAPI-1 is also a general matrix metalloproteinase (MMP) and ADAM inhibitor [2]. |
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References: [1]. Shao MX, Ueki IF, Nadel JA. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11618-23. [2]. Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19796-801. |
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| Description | TAPI-1 is an inhibitor of ADAM17/TACE. | |||||
| Targets | ADAM17/TACE | |||||
| IC50 | ||||||
Quality Control & MSDS
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