Lerociclib (G1T38)
(Synonyms: G1T38) 目录号 : GC34163
G1T38 (Lerociclib) is a novel, potent, selective, and orally bioavailable CDK4/6 inhibitor with IC50 values of 0.001 μM, 0.002 μM and 0.028 μM for CDK4, CDK6 and CDK9 respectively.
Cas No.:1628256-23-4
Sample solution is provided at 25 µL, 10mM.
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G1T38 (Lerociclib) is a novel, potent, selective, and orally bioavailable CDK4/6 inhibitor with IC50 values of 0.001 μM, 0.002 μM and 0.028 μM for CDK4, CDK6 and CDK9 respectively.
G1T38 is highly potent and selective for CDK4/cyclin D1 and CDK6/cyclin D3 over CDK1, CDK2, CDK5 and CDK7 and their respective binding partners. In vitro, G1T38 decreases RB1 (RB) phosphorylation, causes a precise G1 arrest, and inhibits cell proliferation in a variety of CDK4/6-dependent tumorigenic cell lines including breast, melanoma, leukemia, and lymphoma cells with EC50 concentrations as low as 23 nM[1].
In vivo, G1T38 treatment leads to equivalent or improved tumor efficacy compared to the first-in-class CDK4/6 inhibitor, palbociclib, in an ER+ breast cancer xenograft model. Furthermore, G1T38 accumulates in mouse xenograft tumors but not plasma, resulting in less inhibition of mouse myeloid progenitors than after palbociclib treatment. In larger mammals, this difference in pharmacokinetics allows for 28 day continuous dosing of G1T38 in beagle dogs without producing severe neutropenia[1].
[1] John E. Bisi, et al. Oncotarget. 2017, 8(26): 42343-42358.
Cell experiment: | SupT1, Daudi, MCF7, ZR-75-1, A2058, WM2664, and H69 cells are seeded at 1000 cells per well; MV-4-11 and BV173 cells are plated at 4000 cells per well; Tom-1 cells are plated at 8,000 cells per well; NALM-1 cells are plated at 20,000 cells per well in Costar 3903 96 well plates. After 24 hours, plates are dosed with Lerociclib (G1T38) at a nine-point dose concentration from 10 μM to 1 nM. Cell viability is determined after four or six days. Plates are processed on BioTek Synergy2 multi-mode plate reader and data analyzed using GraphPad Prism 5 statistical software[1]. |
Animal experiment: | Mice[1]Female MMTV-NEU mice are used to test the efficacy of Lerocyclib (G1T38) (100 mpk, medicated diet). At time of treatment, body composition is assessed and weight measurements (in grams) are recorded and used as a measure of gross toxicity. Female nude mice are implanted with NSCLC PDX CTG0159 tumor. Mice are then randomized into treatment groups and dosing initiated once tumors reached a volume that fell within the range of 150-300 mm3. 100 mg/kg Lerociclib (G1T38) or vehicle is orally administered for 28 consecutive days. Female NCI Ath/nu mice are implanted with H1975 NSC lung adenocarcinoma model. Once tumors reach an average size of 100-150 mm3, mice are randomized into treatment cohorts. Mice are orally administered daily afatinib (20 mg/kg), erlotinib (70 mg/kg), or Lerociclib (50 or 100 mg/kg), as single agents or in combination (Lerociclib+erlotinib or Lerociclib+afatinib) for the duration of the study. All tumors are measured twice weekly until mice reach tumor burden of 1500 mm3. |
References: [1]. Bisi JE, et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017 Jun 27;8(26):42343-42358. | |
| Cas No. | 1628256-23-4 | SDF | |
| 别名 | G1T38 | ||
| Canonical SMILES | O=C1NCC2(N3C1=CC4=CN=C(NC5=NC=C(N6CCN(C(C)C)CC6)C=C5)N=C43)CCCCC2 | ||
| 分子式 | C26H34N8O | 分子量 | 474.6 |
| 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 | 2.107 mL | 10.5352 mL | 21.0704 mL |
| 5 mM | 0.4214 mL | 2.107 mL | 4.2141 mL |
| 10 mM | 0.2107 mL | 1.0535 mL | 2.107 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。
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Quality Control & SDS
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- Purity: >98.00%
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