PF-4989216
(Synonyms: 4-(4-氰基-2-氟苯基)-2-吗啉-5-(1H-1,2,4-三唑-5-基)噻吩-3-腈) 目录号 : GC12375
An orally bioavailable PI3K inhibitor
Cas No.:1276553-09-3
Sample solution is provided at 25 µL, 10mM.
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Description:
IC50: 2 nM, 142 nM, 65 nM, 1 nM, and 110 nM for p110α, p110β, p110γ, p110δ, and VPS34, respectively.
The constitutive activation of phosphoinositide 3-kinase (PI3K) occurs frequently in many human tumors through either gene mutation in the p110a catalytic subunit of PI3K or functional loss of tumor suppressor PTEN. Patients with small-cell lung cancer have very poor prognosis and survival rates such that an effective targeted therapy is in strong demand for these patients. PF-4989216 is a selective oral PI3K inhibitor.
In vitro: PF-4989216 inhibited PI3K downstream signaling and led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in small-cell lung cancer (SCLC) harboring PIK3CA mutation. In SCLC with PTEN loss, PF-4989216 also inhibited PI3K signaling but did not induce BCL2-interacting mediator-mediated apoptosis nor was there any effect on cell viability or transformation [1].
In vivo: The mouse in vivo results indicate a good correlation between in vitro and in vivo efficacy, and further confirm that PF-4989216 is an effective drug candidate capable of inducing antitumor activity in mice bearing human SCLC tumors with PIK3CA mutation [1].
Clinical trial: Up to now, PF-4989216 is still in the preclinical development stage.
Reference:
[1] Walls M, Baxi SM, Mehta PP, Liu KK, Zhu J, Estrella H, Li C, Zientek M, Zong Q, Smeal T, Yin MJ. Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor PF-4989216. Clin Cancer Res. 2014 Feb 1;20(3):631-43.
Cell experiment: | MTT and CCK-8 assays are performed to determine the general sensitivities of cells to the tested drugs. The human colon carcinoma S1 cell line and ABCG2-overexpressing subline S1-M1-80 are treated with PF-4989216 (0.1, 1 and 10 μM). The human breast carcinoma MCF-7 and ABCG2-overexpressing sublines MCF7-FLV1000 and MCF7-AdVp3000 are treated with PF-4989216 (0.1, 1, 10 and 100 μM).The parental HEK293 and ABCG2-tranfected R482-HEK293 cells are treated with PF-4989216 (0.01, 0.1, 1 and 10 μM). For the reversal of cytotoxicity assays, PF-4989216 or Ko143 or Lapatinib at a nontoxic concentration is added into the cytotoxicity assay, and the extent of reversal is then calculated[2]. |
Animal experiment: | Mice[1]For animal studies, 6-8 week old nu/nu athymic female mice are used. Tumors are established by injecting 2×106 cells suspended 1:1 (v/v) with reconstituted basement membrane. For tumor growth inhibition studies, mice with established tumors of ~150 mm3 are randomized. PF-4989216 (Compound 10) is dosed orally (25, 50, 100 and 200 mg/kg) in a mouse PI3K driven NCI-H1975 xenograft tumor model. Tumor dimensions are measured with vernier calipers, and tumor volumes are calculated. Tumor growth inhibition percentage (TGI %) is calculated. |
References: [1]. Liu KK, et al. Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity. ACS Med Chem Lett. 2011 Sep 19;2(11):809-813. | |
| Cas No. | 1276553-09-3 | SDF | |
| 别名 | 4-(4-氰基-2-氟苯基)-2-吗啉-5-(1H-1,2,4-三唑-5-基)噻吩-3-腈 | ||
| 化学名 | 4-(4-cyano-2-fluorophenyl)-2-morpholino-5-(1H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile | ||
| Canonical SMILES | FC1=C(C(C(C#N)=C2N3CCOCC3)=C(S2)C4=NNC=N4)C=CC(C#N)=C1 | ||
| 分子式 | C18H13FN6OS | 分子量 | 380.4 |
| 溶解度 | DMF: 25 mg/ml,DMSO: 25 mg/ml,DMSO:PBS(pH 7.2) (1:4): 0.2 mg/ml,Ethanol: 1 mg/ml | 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 | 2.6288 mL | 13.1441 mL | 26.2881 mL |
| 5 mM | 0.5258 mL | 2.6288 mL | 5.2576 mL |
| 10 mM | 0.2629 mL | 1.3144 mL | 2.6288 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet