NMS-P515
目录号 : GC36751
NMS-P515 是有效的、口服有效的、立体定向的PARP-1 的抑制剂，Kd 值为16 nM，IC50 值为 27 nM (Hela 细胞中)。有抗肿瘤活性。
Cas No.:1262395-13-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
NMS-P515 is a potent, orally active and stereospecific PARP-1 inhibitor, with a Kd of 16 nM and an IC50 of 27 nM (in Hela cells). Anti-tumor activity[1]. PARP-1|16 nM (Kd)|PARP-1|27 nM (IC50, in Hela cells)
NMS-P515 (80 mg/kg, orally daily for 12 days) exhibits potent antitumor activity in mouse models based pancreatic cancer[1]. Animal Model: Subcutaneously implanted Capan-1 pancreatic (BRCA2-mutated) mouse xenografts[1].
[1]. Papeo G, et al. Discovery of Stereospecific PARP-1 Inhibitor Isoindolinone NMS-P515. ACS Med Chem Lett. 2019 Mar 13;10(4):534-538.
| Cas No. | 1262395-13-0 | SDF | |
| Canonical SMILES | O=C(N)C1=C2C([C@H](C)N(C3CCN(C4CCCCC4)CC3)C2=O)=CC=C1 | ||
| 分子式 | C21H29N3O2 | 分子量 | 355.47 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8132 mL | 14.0659 mL | 28.1318 mL |
| 5 mM | 0.5626 mL | 2.8132 mL | 5.6264 mL |
| 10 mM | 0.2813 mL | 1.4066 mL | 2.8132 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Discovery of Stereospecific PARP-1 Inhibitor Isoindolinone NMS-P515
ACS Med Chem Lett 2019 Mar 13;10(4):534-538.PMID:30996792DOI:PMC6466814
Poly(ADP-ribose) polymerase-1 (PARP-1) is an enzyme involved in signaling and repair of DNA single strand breaks. PARP-1 employs NAD+ to modify substrate proteins via the attachment of poly(ADP-ribose) chains. PARP-1 is a well established target in oncology, as testified by the number of marketed drugs (e.g., Lynparza, Rubraca, Zejula, and Talzenna) used for the treatment of ovarian, breast, and prostate tumors. Efforts in investigating an uncharted region of the previously identified isoindolinone carboxamide series delivered (S)-13 (NMS-P515), a potent inhibitor of PARP-1 both in biochemical (K d: 0.016 μM) and cellular (IC50: 0.027 μM) assays. Cocrystal structure allowed explaining NMS-P515 stereospecific inhibition of the target. After having ruled out potential loss of enantiopurity in vitro and in vivo, NMS-P515 was synthesized in an asymmetric fashion. NMS-P515 ADME profile and its antitumor activity in a mouse xenograft cancer model render the compound eligible for further optimization.