CFTR

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抑制剂选择性比较

CFTR产品

所有产品 CFTR抑制剂(4) CFTR激活剂(2) CFTR调节剂(3) 新CFTR产品

产品目录	产品描述	文献引用	实验数据
S6003	Ataluren (PTC124) Ataluren (PTC124)选择性诱导核糖体转录通读，但不影响正常的终止密码子，在HEK293细胞中EC50为0.1 μM，可以治疗nonsense mutations (如CFTR无义突变引起的CF)造成的家族遗传性疾病。 Phase 3。	Haematologica, 2019, 10.3324/haematol.2018.212118 J Cancer, 2019, 10(2):287-292 Am J Hematol, 2018, 93(4):527-536	Effect of systemic ataluren treatment on mice with the Pax6^Sey+/- phenotype. The black arrowhead indicates the lenticular stalk; the black arrow indicates the cornea; and the asterisk indicates the ciliary margin. WT, Pax6^+/+; Mt, Pax6^Sey/+; L, lens; r, retina. Original magnification, x5.
S7139	CFTRinh-172 CFTRinh-172是电势差不依赖性的选择性CFTR抑制剂，K_i为300 nM，对于MDR1，ATP敏感性钾离子通道或者一系列的转运蛋白没有效果。	Nature, 2019, 567(7748):405-408 PLoS Genet, 2018, 14(11):e1007723 Int J Mol Med, 2018, 41(6):3501-3508	CFTR inhibitor CFTR_inh172 leads to PGCs disorder in early zebrafish embryo. Analysis of localization of nanos1/vasa positive cells in embryos by WISH at 50% Epiboly stage with top view.
S7329	IOWH032 IOWH032是一种合成的CFTR抑制剂，在CHO-CFTR细胞测定中， IC50为1.01 μM。 Phase 2。
S8094	GlyH-101 GlyH-101是一种选择性且可逆的CFTR抑制剂，其K_i为4.3 μM。
S1144	Ivacaftor (VX-770) Ivacaftor (VX-770)是一种CFTR的选择性增强剂，靶向作用于G551D-CFTR和F508del-CFTR，在fisher大鼠甲状腺细胞中EC50分别为100 nM和25 nM。	EMBO J, 2019, 38(4) Cell Rep, 2019, 26(7):1701-1708 J Control Release, 2019, 296:225-231	(A) CFTR Western blot of normal (NL) and CF HBE cultures treated with VX-809 (5 uM) ± VX-770 (5 uM) for 48 hours. “*” indicates the mature, complex glycosylated form of CFTR, band C; “•” indicates the immature band B. (B) Turnover of rescued ΔF508 in BHK-21 cells. ΔF508 was rescued at 27°C in the presence of VX-809 ± VX-770 for 24 hours. After adding cycloheximide (200 ug/ml, 37°C), cells were lysed at the indicated times and analyzed by Western blotting.
S8698	GLPG1837 GLPG1837是新型的CFTR增效剂，对F508del的EC50为3 nM。相较于Ivacaftor，它对具有III类突变的CFTR突变体具有增强效应。
S1565	VX-809 (Lumacaftor) VX-809 (Lumacaftor)通过促进突变型CFTR(F508del-CFTR)的成熟，从而纠正囊性纤维症中常见的CFTR突变，在fisher大鼠甲状腺细胞中EC50为0.1 μM。Phase 3。	Am J Respir Crit Care Med, 2019, 199(1):123-126 Nat Commun, 2019, 10(1):1763 EMBO J, 2019, 38(4)	△F508CFTR diffusion is increased by different correction mechanisms. A, example trajectories from MDCK cell lines for wtCFTR (black) and △F508CFTR rescued by VX-809 treatment in the absence (red) and presence (blue ) of mCh-CFTR-C. B, summary graph for wtCFTR, r△F508CFTR and CFTR△PDZ diffusion in VX-809-treated and control MDCK cell lines. C, example trajectories for MDCK cells transiently expressing 3FLAG-tagged wtCFTR(black), △F508CFTR rescued by VX-809 (red), CFTR△PDZ ( blue ), and △F508CFTR△PDZ rescued by VX-809 (green). D, summary graph for CFTR dif- fusion in VX-809-treated MDCK transiently transfected with 3FLAG-tagged CFTR constructs. E, example trajectories from MDCK cell lines stably expressing wtCFTR ( left ) and △F508CFTR ( right ) treated with thapsigargin ( black)or CoPo-22 (red) or transiently expressing GFP-GRASP55 (blue ). F, graphs for △F508CFTR ( top ) and wtCFTR (bottom) diffusion in MDCK cell lines treated with thapsigargin or CoPo-22 or transiently expressing GFP-GRASP55. For reference, median and interquartile values for wtCFTR diffusive range are shown by dashed lines(bar 1, top ). G, GFP-GRASP55 is Golgi-localized by immunocytochemical analysis (scale bar, 10 μm). Scale bar in A (500 nm) refers to all trajectories. In panels Band D, statistically significant differences in populations are shown (*, p<0.001). SPT data for MDCK cell lines was derived from 140 –788 trajectories and for transiently transfected MDCK cells from 131–298 trajectories.
S7059	Tezacaftor (VX-661) Tezacaftor (VX-661)是第二个F508del CFTR校正药物，协助CFTR蛋白到达细胞表面。Phase 2。	J Cyst Fibros, 2019, 18(5):622-629 Sci Rep, 2018, 8(1):11404 J Cyst Fibros, 2018, 17(5):573-581	(B)ΔISC response to forskolin observed in VX-661-treated CF HBE cells (P = 0.0021, VX661 vs. vehicle) was prevented by chronic VX-770 treatment and significantly different from VX-661-treated cells (#P=0.0126, VX661 vs. VX661+VX770). (C) The response to CFTR inh-172 that was observed in VX-661-treated cells (P = 0.0111, VX661 vs. vehicle) was significantly decreased in VX809+VX770 treated cells (#P = 0.0038, VX661 vs. VX661+VX770). Primary CF HBE cultures (ΔF508/ΔF508) were derived from 3 different patients, and 3-4 replicates were performed per patient.
S8795^New	FDL169 FDL169是CFTR校正剂，用于修复功能缺陷的CFTR蛋白。

产品目录	产品描述	文献引用	实验数据
S6003	Ataluren (PTC124) Ataluren (PTC124)选择性诱导核糖体转录通读，但不影响正常的终止密码子，在HEK293细胞中EC50为0.1 μM，可以治疗nonsense mutations (如CFTR无义突变引起的CF)造成的家族遗传性疾病。 Phase 3。	Haematologica,2019, 10.3324/haematol.2018.212118 J Cancer,2019, 10(2):287-292 Am J Hematol,2018, 93(4):527-536	Effect of systemic ataluren treatment on mice with the Pax6^Sey+/- phenotype. The black arrowhead indicates the lenticular stalk; the black arrow indicates the cornea; and the asterisk indicates the ciliary margin. WT, Pax6^+/+; Mt, Pax6^Sey/+; L, lens; r, retina. Original magnification, x5.
S7139	CFTRinh-172 CFTRinh-172是电势差不依赖性的选择性CFTR抑制剂，K_i为300 nM，对于MDR1，ATP敏感性钾离子通道或者一系列的转运蛋白没有效果。	Nature,2019, 567(7748):405-408 PLoS Genet,2018, 14(11):e1007723 Int J Mol Med,2018, 41(6):3501-3508	CFTR inhibitor CFTR_inh172 leads to PGCs disorder in early zebrafish embryo. Analysis of localization of nanos1/vasa positive cells in embryos by WISH at 50% Epiboly stage with top view.
S7329	IOWH032 IOWH032是一种合成的CFTR抑制剂，在CHO-CFTR细胞测定中， IC50为1.01 μM。 Phase 2。
S8094	GlyH-101 GlyH-101是一种选择性且可逆的CFTR抑制剂，其K_i为4.3 μM。

产品目录	产品描述	文献引用	实验数据
S1144	Ivacaftor (VX-770) Ivacaftor (VX-770)是一种CFTR的选择性增强剂，靶向作用于G551D-CFTR和F508del-CFTR，在fisher大鼠甲状腺细胞中EC50分别为100 nM和25 nM。	EMBO J, 2019, 38(4) Cell Rep, 2019, 26(7):1701-1708 J Control Release, 2019, 296:225-231	(A) CFTR Western blot of normal (NL) and CF HBE cultures treated with VX-809 (5 uM) ± VX-770 (5 uM) for 48 hours. “*” indicates the mature, complex glycosylated form of CFTR, band C; “•” indicates the immature band B. (B) Turnover of rescued ΔF508 in BHK-21 cells. ΔF508 was rescued at 27°C in the presence of VX-809 ± VX-770 for 24 hours. After adding cycloheximide (200 ug/ml, 37°C), cells were lysed at the indicated times and analyzed by Western blotting.
S8698	GLPG1837 GLPG1837是新型的CFTR增效剂，对F508del的EC50为3 nM。相较于Ivacaftor，它对具有III类突变的CFTR突变体具有增强效应。

产品目录

产品描述

文献引用

实验数据

S1144

Ivacaftor (VX-770)

Ivacaftor (VX-770)是一种CFTR的选择性增强剂，靶向作用于G551D-CFTR和F508del-CFTR，在fisher大鼠甲状腺细胞中EC50分别为100 nM和25 nM。

EMBO J, 2019, 38(4)

Cell Rep, 2019, 26(7):1701-1708

J Control Release, 2019, 296:225-231

S8698

GLPG1837

GLPG1837是新型的CFTR增效剂，对F508del的EC50为3 nM。相较于Ivacaftor，它对具有III类突变的CFTR突变体具有增强效应。

产品目录	产品描述	文献引用	实验数据
S1565	VX-809 (Lumacaftor) VX-809 (Lumacaftor)通过促进突变型CFTR(F508del-CFTR)的成熟，从而纠正囊性纤维症中常见的CFTR突变，在fisher大鼠甲状腺细胞中EC50为0.1 μM。Phase 3。	Am J Respir Crit Care Med, 2019, 199(1):123-126 Nat Commun, 2019, 10(1):1763 EMBO J, 2019, 38(4)	△F508CFTR diffusion is increased by different correction mechanisms. A, example trajectories from MDCK cell lines for wtCFTR (black) and △F508CFTR rescued by VX-809 treatment in the absence (red) and presence (blue ) of mCh-CFTR-C. B, summary graph for wtCFTR, r△F508CFTR and CFTR△PDZ diffusion in VX-809-treated and control MDCK cell lines. C, example trajectories for MDCK cells transiently expressing 3FLAG-tagged wtCFTR(black), △F508CFTR rescued by VX-809 (red), CFTR△PDZ ( blue ), and △F508CFTR△PDZ rescued by VX-809 (green). D, summary graph for CFTR dif- fusion in VX-809-treated MDCK transiently transfected with 3FLAG-tagged CFTR constructs. E, example trajectories from MDCK cell lines stably expressing wtCFTR ( left ) and △F508CFTR ( right ) treated with thapsigargin ( black)or CoPo-22 (red) or transiently expressing GFP-GRASP55 (blue ). F, graphs for △F508CFTR ( top ) and wtCFTR (bottom) diffusion in MDCK cell lines treated with thapsigargin or CoPo-22 or transiently expressing GFP-GRASP55. For reference, median and interquartile values for wtCFTR diffusive range are shown by dashed lines(bar 1, top ). G, GFP-GRASP55 is Golgi-localized by immunocytochemical analysis (scale bar, 10 μm). Scale bar in A (500 nm) refers to all trajectories. In panels Band D, statistically significant differences in populations are shown (*, p<0.001). SPT data for MDCK cell lines was derived from 140 –788 trajectories and for transiently transfected MDCK cells from 131–298 trajectories.
S7059	Tezacaftor (VX-661) Tezacaftor (VX-661)是第二个F508del CFTR校正药物，协助CFTR蛋白到达细胞表面。Phase 2。	J Cyst Fibros, 2019, 18(5):622-629 Sci Rep, 2018, 8(1):11404 J Cyst Fibros, 2018, 17(5):573-581	(B)ΔISC response to forskolin observed in VX-661-treated CF HBE cells (P = 0.0021, VX661 vs. vehicle) was prevented by chronic VX-770 treatment and significantly different from VX-661-treated cells (#P=0.0126, VX661 vs. VX661+VX770). (C) The response to CFTR inh-172 that was observed in VX-661-treated cells (P = 0.0111, VX661 vs. vehicle) was significantly decreased in VX809+VX770 treated cells (#P = 0.0038, VX661 vs. VX661+VX770). Primary CF HBE cultures (ΔF508/ΔF508) were derived from 3 different patients, and 3-4 replicates were performed per patient.
S8795^New	FDL169 FDL169是CFTR校正剂，用于修复功能缺陷的CFTR蛋白。

产品目录

产品描述

文献引用

实验数据

S1565