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。
| Cas No. | 2756851-99-5 |
| 分子式 | C29H30ClN5O5 |
| 分子量 | 564.03 |
| 溶解度 | DMSO : 20 mg/mL (35.46 mM; ultrasonic and warming and adjust pH to 3 with HCl and heat to 60°C) |
| 储存条件 | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
| Shipping Condition | Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request |
| 产品描述 | 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 for BRD4 and CK2, respectively. BRD4/CK2-IN-1 has strong anticancer activity without obvious toxicities. BRD4/CK2-IN-1 inducesapoptosisandautophagy-associated cell death in triple-negative breast cancer (TNBC)[1] 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: | |
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. |
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