Gamma-secretase

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研究领域

抑制剂选择性比较

特异性亚型抑制剂

Gamma-secretase产品

所有产品 Gamma-secretase抑制剂(12) Gamma-secretase调节剂(2)

产品目录	产品描述	文献引用	实验数据
S2215	DAPT (GSI-IX) DAPT (GSI-IX)是一种新型γ-secretase抑制剂，抑制 Aβ产生，在HEK 293细胞中IC50为20 nM。	Nature, 2019, 565(7740):505-510 Acta Neuropathol, 2019, 10.1007/s00401-019-01986-1 Cell Res, 2019, 29(2):110-123	Western blotting showing increased unconjugated SUMO1 levels in Notch1 ΔE cells treated with 10 uM DAPT for 3 days. Tubulin was used as a loading control.
S1575	RO4929097 RO4929097是一种γ secretase抑制剂，无细胞试验中IC50为4 nM，抑制Aβ40和Notch的细胞加工，EC50分别为14 nM和5 nM。Phase 2。	Cell Res, 2019, 29(2):110-123 Int J Cancer, 2019, 10.1002/ijc.32293 Mol Cancer Ther, 2019, 18(7):1230-1242
S1594	Semagacestat (LY450139) Semagacestat (LY450139)是一种γ-分泌酶抑制剂，作用于Aβ42，Aβ40和Aβ38，IC50分别为10.9 nM，12.1 nM和12.0 nM，也抑制Notch信号通路，人神经胶质瘤细胞中IC50为14.1 nM。Phase 3。	Proc Natl Acad Sci USA, 2017, 114(50):E10782-E10791 J Biol Chem, 2016, 291(4):1538-51 PLoS One, 2015, 10(4):e0122451	HEK/APPswe cells were either left non-treated (-) or exposed to the γ-secretase inhibitor (GSI) semagacestat (+) for 19 h prior to cell harvesting and membrane preparation (Substrate accumulation). Exposure of cells with GSI prior to membrane preparation results in higher Aβ1-42 and Aβx-42 signals as compared to membranes derived from non-GSI treated cells. Direct addition of semagacestat to the membranes in the novo Aβ production assay inhibited Aβ production (Semagacestat (1 µM)). The amount of Aβx-42 is higher than Aβ1-42 suggesting that C83 is the major substrate for the Aβ42 signal detected.
S2660	MK-0752 MK-0752是一种适度有效的γ-secretase（γ-分泌酶）抑制剂，降低Aβ40产量，IC50为5 nM。Phase 1/2。	Neoplasia, 2018, 21(1):93-105 Proc Natl Acad Sci USA, 2017, 114(50):E10782-E10791 Oncol Lett, 2016, 12(4):2900-2905	HES1 expression after treatment with clinically available GSIs R04929097, BMS-708163, LY450139, and MK-0752 as determined by qRT-PCR.
S1262	Avagacestat (BMS-708163) Avagacestat (BMS-708163)是口服生物有效的，选择性的γ-分泌酶抑制剂，作用于Aβ40和Aβ42时，IC50分别为0.3 nM和0.27 nM，比作用于Notch选择性高193倍。Phase 2。	Cancer Cell, 2019, 36(1):68-83 Acta Pharmacol Sin, 2018, 39(2):177-183 Sci Rep, 2016, 6:33427	A panel of GICs lines was treated with various concentrations of γ secretase inhibitors BMS-708163. Cells were treated with increasing concentrations of γ secretase inhibitors in triplicate wells for 72 hours, and cell viability was assessed by CellTiter-Blue assay as described in Materials and Methods. The results shown are of a single experiment with three independent replicates cell viability was measured by CellTiter-Blue assay. The graph depicts cell viability at 72 hours. Cell viability in the vehicle control was considered as to be 100%.
S2711	Dibenzazepine (YO-01027) Dibenzazepine (YO-01027)是一种二肽γ-secretase抑制剂，作用于APPL和Notch分裂，无细胞试验中IC50分别为2.6 nM和2.9 nM。	Cancer Cell, 2019, 35(5):752-766 Cell Res, 2019, 29(2):110-123 Biomed Pharmacother, 2019, 109:93-102	Tumor spheres formation assay. Images were taken at 48 h after treating the cells with various formulations of YO (scale bar 100 um).
S2714	LY411575 LY411575是一种有效的γ-secretase抑制剂，在表达APP或NΔE的HEK293细胞中IC50为0.078 nM/0.082 nM(基于膜/细胞)，也抑制Notch分裂，IC50为0.39 nM。	Diabetes, 2018, 67(1):58-70 Exp Cell Res, 2017, 10.1016/j.yexcr.2017.08.022 Cell Rep, 2014, 6(3):467-81	(E) Quantitation of lumen from A-D. (F) RNA isolated from 6d acini and expression of NOTCH1 measured by qRT-PCR in triplicate. P values are * <.01, *** <0.001.
S8018	Nirogacestat (PF-03084014, PF-3084014) Nirogacestat (PF-03084014, PF-3084014) 是一种选择性gamma-secretase抑制剂，在无细胞试验中IC50为6.2 nM。Phase 2。	Mol Ther Oncolytics, 2019, 13:58-66 Front Immunol, 2019, 10:162 J Cell Physiol, 2019, 234(5):5940-5952	The expression of p-EGFR and NICD was assessed by western blot after treatment for 3 d.
S8280	IMR-1 IMR-1是靶向转录激活过程的新型Notch抑制剂，其IC50为26 μM。
S7673	L-685,458 L-685,458 是一种beta PP gamma-secretase活性的特异性有效抑制剂，其K_i值为17 nM.。		The levels of Aβ produced by neuronal differentiated NSCs in response to vehicle (0.1% DMSO), 10μM BSI IV, 10μM L685,458, or the indicated compounds at 3μM or 10μM for 24hours
S7399	FLI-06 FLI-06 是一种靶向Notch信号通路的新型抑制剂，EC50是2.3 μM。	Am J Cancer Res, 2019, 9(9):1938-1956 Med Sci Monit, 2018, 24:8213-8223 Biochem Biophys Res Commun, 2018, 495(1):246-253	In the presence of FLI-06 (100 nM), wound healing assay was conducted to evaluate the cell motility after transfection. Data were from three independent experiments and were Mean ± SD. values. **P < 0.01 compared to cells transfected with vector, ##P < 0.01 compared to cells transfected with ZFR. Scale bar represents 200 μm.
S7169	Crenigacestat (LY3039478) Crenigacestat (LY3039478)是一种有效的Notch抑制剂，IC50为0.41 nM。	Eur Rev Med Pharmacol Sci, 2018, 22(13):4121-4127	Effect of LY3039478 on Hes protein in SGC7901/DDP cells. A, Protein expression of Hes-1 by Western blot. B, Expression level of Hes-1 by Western blot experiment. (p < 0.05 control with LY3039478 0 μmol/L group; *p < 0.01 control with LY3039478 0 μmol/L group).
S7323	CHF 5074 CHF5074是gamma-secretase调节剂，可减少Aβ42和Aβ40的分泌。它可抑制COX1和COX2，IC50大于100 μM。
S8603	NGP 555 NGP 555是γ-secretase的小分子调节剂，在靶向脂质膜的临床前实验中，NGP 555具有良好的口服吸收率、大脑渗透性、中枢神经系统活性和特异性。

产品目录	产品描述	文献引用	实验数据
S2215	DAPT (GSI-IX) DAPT (GSI-IX)是一种新型γ-secretase抑制剂，抑制 Aβ产生，在HEK 293细胞中IC50为20 nM。	Nature,2019, 565(7740):505-510 Acta Neuropathol,2019, 10.1007/s00401-019-01986-1 Cell Res,2019, 29(2):110-123	Western blotting showing increased unconjugated SUMO1 levels in Notch1 ΔE cells treated with 10 uM DAPT for 3 days. Tubulin was used as a loading control.
S1575	RO4929097 RO4929097是一种γ secretase抑制剂，无细胞试验中IC50为4 nM，抑制Aβ40和Notch的细胞加工，EC50分别为14 nM和5 nM。Phase 2。	Cell Res,2019, 29(2):110-123 Int J Cancer,2019, 10.1002/ijc.32293 Mol Cancer Ther,2019, 18(7):1230-1242
S1594	Semagacestat (LY450139) Semagacestat (LY450139)是一种γ-分泌酶抑制剂，作用于Aβ42，Aβ40和Aβ38，IC50分别为10.9 nM，12.1 nM和12.0 nM，也抑制Notch信号通路，人神经胶质瘤细胞中IC50为14.1 nM。Phase 3。	Proc Natl Acad Sci USA,2017, 114(50):E10782-E10791 J Biol Chem,2016, 291(4):1538-51 PLoS One,2015, 10(4):e0122451	HEK/APPswe cells were either left non-treated (-) or exposed to the γ-secretase inhibitor (GSI) semagacestat (+) for 19 h prior to cell harvesting and membrane preparation (Substrate accumulation). Exposure of cells with GSI prior to membrane preparation results in higher Aβ1-42 and Aβx-42 signals as compared to membranes derived from non-GSI treated cells. Direct addition of semagacestat to the membranes in the novo Aβ production assay inhibited Aβ production (Semagacestat (1 µM)). The amount of Aβx-42 is higher than Aβ1-42 suggesting that C83 is the major substrate for the Aβ42 signal detected.
S2660	MK-0752 MK-0752是一种适度有效的γ-secretase（γ-分泌酶）抑制剂，降低Aβ40产量，IC50为5 nM。Phase 1/2。	Neoplasia,2018, 21(1):93-105 Proc Natl Acad Sci USA,2017, 114(50):E10782-E10791 Oncol Lett,2016, 12(4):2900-2905	HES1 expression after treatment with clinically available GSIs R04929097, BMS-708163, LY450139, and MK-0752 as determined by qRT-PCR.
S1262	Avagacestat (BMS-708163) Avagacestat (BMS-708163)是口服生物有效的，选择性的γ-分泌酶抑制剂，作用于Aβ40和Aβ42时，IC50分别为0.3 nM和0.27 nM，比作用于Notch选择性高193倍。Phase 2。	Cancer Cell,2019, 36(1):68-83 Acta Pharmacol Sin,2018, 39(2):177-183 Sci Rep,2016, 6:33427	A panel of GICs lines was treated with various concentrations of γ secretase inhibitors BMS-708163. Cells were treated with increasing concentrations of γ secretase inhibitors in triplicate wells for 72 hours, and cell viability was assessed by CellTiter-Blue assay as described in Materials and Methods. The results shown are of a single experiment with three independent replicates cell viability was measured by CellTiter-Blue assay. The graph depicts cell viability at 72 hours. Cell viability in the vehicle control was considered as to be 100%.
S2711	Dibenzazepine (YO-01027) Dibenzazepine (YO-01027)是一种二肽γ-secretase抑制剂，作用于APPL和Notch分裂，无细胞试验中IC50分别为2.6 nM和2.9 nM。	Cancer Cell,2019, 35(5):752-766 Cell Res,2019, 29(2):110-123 Biomed Pharmacother,2019, 109:93-102	Tumor spheres formation assay. Images were taken at 48 h after treating the cells with various formulations of YO (scale bar 100 um).
S2714	LY411575 LY411575是一种有效的γ-secretase抑制剂，在表达APP或NΔE的HEK293细胞中IC50为0.078 nM/0.082 nM(基于膜/细胞)，也抑制Notch分裂，IC50为0.39 nM。	Diabetes,2018, 67(1):58-70 Exp Cell Res,2017, 10.1016/j.yexcr.2017.08.022 Cell Rep,2014, 6(3):467-81	(E) Quantitation of lumen from A-D. (F) RNA isolated from 6d acini and expression of NOTCH1 measured by qRT-PCR in triplicate. P values are * <.01, *** <0.001.
S8018	Nirogacestat (PF-03084014, PF-3084014) Nirogacestat (PF-03084014, PF-3084014) 是一种选择性gamma-secretase抑制剂，在无细胞试验中IC50为6.2 nM。Phase 2。	Mol Ther Oncolytics,2019, 13:58-66 Front Immunol,2019, 10:162 J Cell Physiol,2019, 234(5):5940-5952	The expression of p-EGFR and NICD was assessed by western blot after treatment for 3 d.
S8280	IMR-1 IMR-1是靶向转录激活过程的新型Notch抑制剂，其IC50为26 μM。
S7673	L-685,458 L-685,458 是一种beta PP gamma-secretase活性的特异性有效抑制剂，其K_i值为17 nM.。		The levels of Aβ produced by neuronal differentiated NSCs in response to vehicle (0.1% DMSO), 10μM BSI IV, 10μM L685,458, or the indicated compounds at 3μM or 10μM for 24hours
S7399	FLI-06 FLI-06 是一种靶向Notch信号通路的新型抑制剂，EC50是2.3 μM。	Am J Cancer Res,2019, 9(9):1938-1956 Med Sci Monit,2018, 24:8213-8223 Biochem Biophys Res Commun,2018, 495(1):246-253	In the presence of FLI-06 (100 nM), wound healing assay was conducted to evaluate the cell motility after transfection. Data were from three independent experiments and were Mean ± SD. values. **P < 0.01 compared to cells transfected with vector, ##P < 0.01 compared to cells transfected with ZFR. Scale bar represents 200 μm.
S7169	Crenigacestat (LY3039478) Crenigacestat (LY3039478)是一种有效的Notch抑制剂，IC50为0.41 nM。	Eur Rev Med Pharmacol Sci,2018, 22(13):4121-4127	Effect of LY3039478 on Hes protein in SGC7901/DDP cells. A, Protein expression of Hes-1 by Western blot. B, Expression level of Hes-1 by Western blot experiment. (p < 0.05 control with LY3039478 0 μmol/L group; *p < 0.01 control with LY3039478 0 μmol/L group).

产品目录

产品描述

文献引用

实验数据

S7323

CHF 5074

CHF5074是gamma-secretase调节剂，可减少Aβ42和Aβ40的分泌。它可抑制COX1和COX2，IC50大于100 μM。

S8603

NGP 555

NGP 555是γ-secretase的小分子调节剂，在靶向脂质膜的临床前实验中，NGP 555具有良好的口服吸收率、大脑渗透性、中枢神经系统活性和特异性。

Tags: Gamma-secretase inhibition | Gamma-secretase inhibitor Notch | Gamma-secretase activity | Gamma-secretase assay | Gamma-secretase cleavage | Gamma-secretase inhibitor in clinical trial | Gamma-secretase inhibitor review