K-975 是一种有效的，具有选择性和口服活性的TEAD抑制剂，可强烈抑制YAP1/TAZ和 TEAD 之间的蛋白质-蛋白质相互作用。K-975 通过丙烯酰胺结构与位于 TEAD 棕榈酸酯结合口袋中的 Cys359 共价结合。 K-975 具有抗恶性胸膜间皮瘤的活性。
| 生物活性 | K-975 is a potent, selective and orally activeTEADinhibitor, with a strong inhibitory effect against protein-protein interactions betweenYAP1/TAZand TEAD. K-975 covalently binds to Cys359 located in the palmitate-binding pocket of TEAD via an acrylamide structure. K-975 exhibits antitumor activity on malignant pleural mesothelioma[1]. |
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体外研究
(In Vitro) | K-975 (0.1-10000 nM; 144 h) inhibits the cell proliferation of NF2-non-expressing malignant pleural mesothelioma (MPM) cell lines[1].
K-975 (10-10000 nM; 24 h) inhibits protein-protein interaction (PPI) between Halo-YAP and endogenous TEAD1/4 and Halo-TAZ and TEAD1/4 in NCI-H226 cells[1].
K-975 (0.1-10000 nM; 24 h) strongly inhibits the reporter activity in NCI-H661/CTGF-Luc cells, with the maximum inhibition of ~70%, and does not inhibit the reporter activity in NCI-H661/NRF2-Luc cells[1].
K-975 (1-10000 nM; 24 h) decreases the expressions ofCTGF,IGFBP3, andNPPBmRNAs, and increases the expression ofFBXO32mRNA in NCI-H226 cells[1].
Cell Proliferation Assay[1] | Cell Line: | NF2-non-expressing MPM and NF2-expressing malignant MPM cells | | Concentration: | 0.1, 1, 10, 100, 1000, 10000 nM | | Incubation Time: | 144 hours | | Result: | Had a stronger inhibitory effect against NF2-non-expressing cell lines than NF2-expressing cell lines.
Inhibited the proliferation of MSTO-211H cells, an NF2-expressing cell line. |
Western Blot Analysis[1] | Cell Line: | NCI-H226 cells | | Concentration: | 10, 100, 1000, 10000 nM | | Incubation Time: | 24 hours | | Result: | Inhibited TEAD1-YAP1 PPI and TEAD4-YAP1 PPI.
Inhibited TEAD1-TAZ PPI and TEAD4-TAZ PPI. |
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体内研究
(In Vivo) | K-975 (10-300 mg/kg; p.o. twice a day for 14 days) inhibits the tumor growth by inhibiting YAP1/TAZ-TEAD signaling in MPM xenograft mouse models[1].
| Animal Model: | Male SCID mice (5 weeks) injected with NCI-H226 or MSTO-211H cells[1] | | Dosage: | 10, 30, 100, 300 mg/kg | | Administration: | P.o. twice a day for 14 days | | Result: | Exhibited strong anti-tumor effect in MPM s.c. xenograft mouse models.
Decreased the expressions ofCTGF,IGFBP3, andNPPB, and increased the expression ofFBXO32in the NCI-H226 xenograft model. |
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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 : 220 mg/mL(764.58 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.4754 mL | 17.3768 mL | 34.7536 mL | | 5 mM | 0.6951 mL | 3.4754 mL | 6.9507 mL | | 10 mM | 0.3475 mL | 1.7377 mL | 3.4754 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 5.5 mg/mL (19.11 mM); Suspended solution; Need ultrasonic
此方案可获得 5.5 mg/mL (19.11 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 55.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 5.5 mg/mL (19.11 mM); Clear solution
此方案可获得 ≥ 5.5 mg/mL (19.11 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 55.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 5.5 mg/mL (19.11 mM); Clear solution
此方案可获得 ≥ 5.5 mg/mL (19.11 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 55.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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