PARP1/BRD4-IN-2 是一种有效且具有选择性的PARP1和BRD4抑制剂，IC50分别为 197 nM 和 238 nM。PARP1/BRD4-IN-2 抑制 DNA 损伤修复，阻止 G0/G1 细胞周期转变，诱导细胞凋亡 (apoptosis)。PARP1/BRD4-IN-2 在MDA-MB-468小鼠异种移植瘤模型中具有抗肿瘤活性。PARP1/BRD4-IN-2 可用于三阴性乳腺癌 (TNBC) 的研究。
| 生物活性 | PARP1/BRD4-IN-2 is a potent and selectivePARP1andBRD4inhibitor withIC50values of 197 nM and 238 nM, respectively. PARP1/BRD4-IN-2 inhibits DNA damage repair, arrests G0/G1 transition and inducesapoptosis. PARP1/BRD4-IN-2 has anti-tumor activity in MDA-MB-468 xenograft mouse model. PARP1/BRD4-IN-2 can be used for researching triple-negative breastcancer(TNBC)[1]. |
| IC50& Target[1] | BRD4 238 nM (IC50) | PARP1 197 nM (IC50) |
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体外研究
(In Vitro) | PARP1/BRD4-IN-2 (compound BP44) can directly bind to BRD4 and PARP1 in MDA-MB-468 cells and improve their thermal stability[1].
PARP1/BRD4-IN-2 has antiproliferative activity against MDA-MB-231 and MDA-MB-468 with IC50s of 6.61±0.58 μM and 3.01±0.83 μM, respectively[1].
PARP1/BRD4-IN-2 (5, 10, and 20 μM) down-regulates Bcl-2 and up-regulates Bax and cleaved caspase3 at 20 μM; inhibits colony formation and promotes cell apoptosis in MDA-MB-468 cells[1].
PARP1/BRD4-IN-2 (5, 10, and 20 μM) down-regulates DNA damage-related proteins CtIP, Mre11, Rad51, and p-RPA32 dose-dependently; causes DNA damage repair defects by down-regulating Rad51 and p-RPA32[1].
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体内研究
(In Vivo) | PARP1/BRD4-IN-2 (40 and 80 mg/kg; IG, for 16 days) significantly inhibits tumor growth in xenograft mice and without significant toxicities, and significantly down-regulates the expression of CtIP, c-Myc, PAR, and Rad51 in tumor tissues[1].
Pharmacokinetic Parameters of PARP1/BRD4-IN-2 in Sprague-Dawley rats[1].
| IV (1 mg/kg) | PO (10 mg/kg) | | T1/2(h) | 3.02 ± 0.57 | 3.33 ± 0.71 | | Cmax(ng/mL) | 258 ± 11 | 242 ± 6 | | AUC0-t(ng/mL·h) | 629 ± 49 | 1489 ± 130 | | AUC0-∞(ng/mL·h) | 642 ± 36 | 1530 ± 146 | | VZ(L/kg) | 21.1 ± 2.6 | | | CL (mL/min/kg) | 33.7 ± 1.5 | | | F (%) | | 23.8 ± 1.3 |
| Animal Model: | Female BALB/c nude mice (implanted subcutaneously with MDA-MB-468 tumor cells)[1] | | Dosage: | 40 and 80 mg/kg | | Administration: | IG, for 16 days | | Result: | Significantly inhibited tumor growth and exhibits no significant toxicities; and significantly down-regulated the expression of CtIP, c-Myc, PAR, and Rad51 in tumor tissues. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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