TED-347 是一种有效，不可逆且共价的YAP-TEAD蛋白质-蛋白质相互作用变构抑制剂，对 TEAD4oYap1 蛋白质-蛋白质相互作用的EC50为 5.9 μM。TED-347 与 TEAD4 中央口袋内的 Cys-367 特异性共价结合，Ki为 10.3 μM。TED-347 可以阻断 TEAD 的转录活性，并且具有抗肿瘤活性。
| 生物活性 | TED-347 is a potent, irreversible, covalent and allosteric inhibitor atYAP-TEAD protein-protein interactionwith anEC50of 5.9 μM for TEAD4·Yap1 protein-protein interaction. TED-347 specifically and covalently bonds with Cys-367 within the central pocket of TEAD4 with aKiof 10.3 μM. TED-347 blocks TEAD transcriptional activity and has antitumor activity[1]. |
| IC50& Target | IC50: 5.9 μM (TEAD4·Yap1 protein-protein interaction)[1] |
体外研究
(In Vitro) | TED-347 (0.5-100 μM; 48 hours) inhibits GBM43 cancer cell viability[1].
TED-347 (5 μM; 48 hours) inhibits co-immunoprecipitation of Myc-tagged TEAD4 with FLAG-tagged Yap1[1].
TED-347 (10 μM; 48 hours) shows a significant reduction in CTGF transcript levels[1].
TED-347 (0.5-100 μM; 24 hours) reduces reporter activity in cells transfected with a TEAD reporter. TED-347 (0.5-100 μM) also inhibits TEAD4 transcriptional activity in GBM43 cells[1].
TED-347 is selective for TEADs and inhibits TEAD2 with the same efficacy. TED-347 (0.1-100 μM; 24-48 hours) inhibits TEAD4 binding to full-length Yap1 in dose- and time-dependent manner. TED-347 (1-100 μM) shows no inhibition of uPARouPA or Cav2.2 αoβ protein-protein interactions. Non-covalent binding of TED-347 to TEAD4 exhibits little change to the TEAD4oYap1 binding affinity[1].
TED-347 has the maximum rate of inactivation of 0.038 hours, corresponding to a t1/2∞of 18.2 hours[1].
Cell Viability Assay[1] | Cell Line: | GBM43 glioblastoma cell lines | | Concentration: | 0.5, 1, 10, 100 μM | | Incubation Time: | 48 hours | | Result: | Inhibited GBM43 cancer cell viability and inhibited GBM43 cell viability by 30% at 10 μM. |
Western Blot Analysis[1] | Cell Line: | HEK-293 cells | | Concentration: | 5 μM | | Incubation Time: | 48 hours | | Result: | Showed a significant loss of co-immunoprecipitation of Myc-tagged TEAD4 with FLAG-tagged Yap1. |
RT-PCR[1] | Cell Line: | HEK-293 cells | | Concentration: | 10 μM | | Incubation Time: | 48 hours | | Result: | Showed a significant reduction in CTGF transcript levels versus control cells and had no inhibition on TEAD mutant transcriptional activity and protein-protein interactions in cell culture. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(318.78 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.1878 mL | 15.9388 mL | 31.8776 mL | | 5 mM | 0.6376 mL | 3.1878 mL | 6.3755 mL | | 10 mM | 0.3188 mL | 1.5939 mL | 3.1878 mL |
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