瑞卡帕布樟脑磺酸盐

中文名称:

瑞卡帕布樟脑磺酸盐

中文同义词:

瑞卡帕布樟脑磺酸盐;芦卡帕利;英文同义词: RUCAPARIB CAMSYLATE;PARP抑制剂(RUCAPARIB CAMSYLATE)

英文名称:

Rucaparib Camsylate

英文同义词:

Rucaparib Camsylate;8‐Fluoro‐2‐(4‐methylaminomethyl‐phenyl)‐1,3,4,5‐tetrahydro‐azepino[5,4,3‐cd] indol‐6‐one (S)‐camphorsulfonate Salt;Rucaparib Camphosulfonate;Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S,4R)-, compd. with 8-fluoro-1,3,4,5-tetrahydro-2-[4-[(methylamino)methyl]phenyl]-6H-pyrrolo[4,3,2-ef][2]benzazepin-6-one (1:1)

CAS号:

1859053-21-6

分子式:

C29H34FN3O5S

分子量:

555.6607632

EINECS号:

相关类别:

细胞生物学试剂;医药原料

Mol文件:

1859053-21-6.mol

生物活性

Rucaparib Camsylate 是 PARP 的抑制剂，对 PARP1 的 Ki 值为 1.4 nM。Rucaparib Camsylate 也可结合 PARP 其他八个结构域。

靶点

PARP-1 1.4 nM (Ki)

PARP-1 1.4 nM (Ki)

体外研究

Rucaparib is the most potent PARP inhibitor in enzyme assays (K i , 1.4 nM), and a possible N-demethylation metabolite of AG14644. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.

体内研究

Rucaparib and AG14584 significantly (P < 0.05) increases temozolomide toxicity. Rucaparib (1 mg/kg) significantly increases temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) results in a 50% increase in the temozolomide-induced tumor growth delay. Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.