LY2835219 free base
(Synonyms: 阿贝西利,CDK4/6 dual inhibitor;LY 2835219 (free base);LY-2835219 (free base)) 目录号 : GC11823
LY2835219 free base是 CDK4 和 CDK6 的强效选择性抑制剂，在非细胞实验中的 IC50 分别为 2nM 和 10nM。
Cas No.:1231929-97-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | Colo-205 colorectal cells |
Preparation Method | Colo-205 colorectal cells treated with LY2835219 free base (0.001-10μM) for 24h. |
Reaction Conditions | LY2835219 free base: 0.001-10μM; 24h |
Applications | LY2835219 free base treated with Colo-205 colorectal cells showed a concentration-dependent inhibition of p-Rb and a corresponding arrest of cells in G1 (2 N DNA content), resulting in a decreased number of cells due to inhibition of proliferation. |
| Animal experiment [2]: | |
Animal models | Colo-205 human xenograft tumor model |
Preparation Method | LY2835219 free base was formulated in 1 % hydroxyethyl cellulose + 0.1 % antifoam in 25mM PBS pH 2 and administered orally by gavage (final volume 0.2 mL) at the indicated dose and schedule. |
Dosage form | LY2835219 free base (50mg/kg; po; 56d) |
Applications | LY2835219 free base is effective and well tolerated when administered up to 56 days in Colo-205 human xenograft tumor mice without significant loss of body weight or tumor outgrowth. |
References: | |
LY2835219 free base is a potent and selective inhibitor of CDK4 and CDK6 with IC50 of 2nM and 10nM in cell-free assays, respectively[1].
LY2835219 free base (0.001-10μM; 24h) inhibited p-Rb in a concentration-dependent manner, resulting in cell arrest in the G1 phase (2 N DNA content) and a decrease in cell number due to inhibition of proliferation. LY2835219 free base inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells[2]. LY2835219 free base (0.1, 0.2 and 0.4μM; 24h) potentiated the cytotoxicity of conventional chemotherapeutic agents in ABCB1 and ABCG2-overexpressing cells[3].
LY2835219 free base (50mg/kg; po; 56d) was effective and well tolerated in mice bearing Colo-205 xenograft tumors. After administration for up to 56days, there was no significant weight loss in mice and no significant tumor growth[2]. LY2835219 free base (45mg/kg; po; 14d) combined with RAD001 had a synergistic anti-tumor effect on HNSCC xenograft tumors[4].
References:
[1].Corona SP, Generali D. Abemaciclib: a CDK4/6 inhibitor for the treatment of HR+/HER2- advanced breast cancer. Drug Des Devel Ther. 2018 Feb 16;12:321-330.
[2]. Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37.
[3]Wu T, Chen Z, To KKW, Fang X, Wang F, Cheng B, Fu L. Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42.
[4]. Ku BM, Yi SY, Koh J, Bae YH, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma. Oncotarget. 2016 Mar 22;7(12):14803-13.
LY2835219 free base是 CDK4 和 CDK6 的强效选择性抑制剂，在非细胞实验中的 IC50 分别为 2nM 和 10nM[1]。
LY2835219 free base（0.001-10μM，24h）以浓度依赖性方式抑制 p-Rb，导致细胞停滞在 G1 期（2 N DNA 含量），细胞数量因增殖受抑制而减少。LY2835219 free base以低纳摩尔的效价抑制 CDK4 和 CDK6，抑制 Rb 磷酸化，导致 G1 期停滞和增殖抑制，其活性对 Rb 细胞具有特异性[2]。LY2835219 free base（0.1、0.2 和 0.4μM；24h）可增强传统化疗药物对 ABCB1 和 ABCG2 基因敲除细胞的细胞毒性[3]。
LY2835219 free base （50mg/kg；po；56d）对 Colo-205 异种移植肿瘤小鼠有效且耐受性良好，给药长达 56 天，小鼠体重无明显下降，肿瘤无明显生长[2]。LY2835219 free base（45mg/kg；po；14d）与 RAD001 联用对 HNSCC 异种移植瘤有协同抗肿瘤作用[4]。
| Cas No. | 1231929-97-7 | SDF | |
| 别名 | 阿贝西利,CDK4/6 dual inhibitor;LY 2835219 (free base);LY-2835219 (free base) | ||
| 化学名 | N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine | ||
| Canonical SMILES | CCN1CCN(CC2=CN=C(NC3=NC=C(F)C(C4=CC5=C(N=C(C)N5C(C)C)C(F)=C4)=N3)C=C2)CC1 | ||
| 分子式 | C27H32F2N8 | 分子量 | 506.59 |
| 溶解度 | ≥ 4.83 mg/mL in DMSO with ultrasonic and warming, ≥ 6.34 mg/mL in EtOH with gentle warming | 储存条件 | 4°C, protect from light |
| 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 | 1.974 mL | 9.8699 mL | 19.7398 mL |
| 5 mM | 0.3948 mL | 1.974 mL | 3.948 mL |
| 10 mM | 0.1974 mL | 0.987 mL | 1.974 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。