BRD4/CK2-IN-1 是一种首次高效、口服有效的BRD4/CK2(含溴结构域蛋白 4/酪蛋白激酶 2) 双靶点抑制剂。BRD4/CK2-IN-1 对 BRD4 和 CK2 的IC50值分别为 180 nM 和 230 nM。BRD4/CK2-IN-1具有很强的抗癌活性，且无明显毒性。BRD4/CK2-IN-1 在三阴性乳腺癌 (TNBC) 中诱导细胞凋亡和自噬相关的细胞死亡。
| 生物活性 | BRD4/CK2-IN-1 is the first highly effective and oral active dual-target inhibitor ofBRD4/CK2(bromodomain-containing protein 4/casein kinase 2), withIC50s of 180 nM and 230 nM forBRD4andCK2, respectively. BRD4/CK2-IN-1 has strong anticancer activity without obvious toxicities. BRD4/CK2-IN-1 inducesapoptosisandautophagy-associated cell death in triple-negative breastcancer(TNBC)[1] |
| IC50& Target[1] | BRD4 180 nM (IC50) | CK2 230 nM (IC50) |
|
体外研究
(In Vitro) | BRD4/CK2-IN-1 (compound 44e) (0-25 μM; 24 hours) has anti-proliferation effect withIC50s of 2.66 and 3.52 μM in MDA-MB-231 and MDA-MB-468 cells, respectively[1].
BRD4/CK2-IN-1 (0-10 μM; 24 hours) dose-dependently induces apoptosis of MDA-MB-231 and MDA-MB-468 cells[1].
BRD4/CK2-IN-1 (0-10 μM; 24 hours) dose-dependently downregulates Bcl-2 but upregulates Bax and cleaved caspase-3[1].
BRD4/CK2-IN-1 (0-10 μM; 24 hours) significantly downregulates the autophagy substrate p62 and up-regulated beclin-1 and LC3II in MDA-MB-231 and MDA-MB[1].
Cell Viability Assay[1] | Cell Line: | MDA-MB-231, MDA-MB-468 cells | | Concentration: | 0, 0.19, 0.39, 0.78, 1.56, 3.13, 6.25, 12.5, 25 μM | | Incubation Time: | 24 hours | | Result: | Showed anti-proliferative rates in MDA-MB-231 and MDA-MB-468 cells (IC50= 2.66 and 3.52 μM, respectively). |
Apoptosis Analysis[1] | Cell Line: | MDA-MB-231, MDA-MB-468 cells | | Concentration: | 0, 2.5, 5, 10 μM | | Incubation Time: | 24 hours | | Result: | Dose-dependently induced apoptosis of MDA-MB-231 and MDA-MB-468 cells. |
Western Blot Analysis[1] | Cell Line: | MDA-MB-231, MDA-MB-468 cells | | Concentration: | 0, 2.5, 5, 10 μM | | Incubation Time: | 24 hours | | Result: | Dose-dependently downregulated Bcl-2 but upregulated Bax and cleaved caspase-3. |
| Cell Line: | | | Concentration: | | | Incubation Time: | | | Result: | |
|
体内研究
(In Vivo) | BRD4/CK2-IN-1 (25 and 50 mg/kg; intragastric administration; daily for 19 days) inhibits tumor growth in TNBC xenograft models[1].
BRD4/CK2-IN-1 (25 and 50mg/kg; intragastric administration; daily for 19 days) shows weak toxicity measured by body weight loss in the MDA-MB-231 and MDA-MB-468 xenograft models[1].
Preliminary Assessment of Pharmacokinetics (PK) profile of BRD4/CK2-IN-1[1].
| Parameter | iv (1 mg/kg) | po (10 mg/kg) | | T1/2(h) | 4.21±0.57 | 5.14±0.71 | | Cmax(ng/mL) | 237±11 | 206±6 | | AUC0-t(ng·h/mL) | 579±49 | 2079±130 | | AUC0-∞(ng·h/mL) | 588±36 | 2090±146 | | VZ(L/kg) | 21.1±2.6 | | | CL ((mL/min)/kg) | 57.4±1.3 | | | F(%) | | 32.5 |
| Animal Model: | Female nude mice (BALB/c, 6-8 weeks, 20-22 g) bearing MDA-MB-231 cells[1] | | Dosage: | 25 and 50 mg/kg | | Administration: | Intragastric administration; daily for 19 days | | Result: | Had the most pronounced tumor growth inhibition (TGI) (63.8%) in the MDA-MB-231 xenograft tumor model at 50 mg/kg. |
|
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 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 |
|
| 溶解性数据 | In Vitro: DMSO : 20 mg/mL(35.46 mM;ultrasonic and warming and adjust pH to 3 with HCl and heat to 60℃) 配制储备液 | 1 mM | 1.7730 mL | 8.8648 mL | 17.7296 mL | | 5 mM | 0.3546 mL | 1.7730 mL | 3.5459 mL | | 10 mM | 0.1773 mL | 0.8865 mL | 1.7730 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。 |
m.cnreagent.com