CHMFL-ABL-053
目录号 : GC17294CHMFL-ABL-053 (Compound 18a) 是一种有效的、选择性的、可口服的 BCR-ABL、SRC 和 p38 激酶抑制剂,对 ABL1、SRC 和 p38 的 IC50 值分别为 70、90 和 62 nM。
Cas No.:1808287-83-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
CHMFL-ABL-053 (compound 18a) is a BCR-ABL inhibitor with ABL1: IC50 of 70 nM. CHMFL-ABL-053 is derived from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF 7). [1]
CHMFL-ABL-053 inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM) and MEG 01 (GI50 = 16 nM), through significant suppression of the BCR-ABL auto phosphorylation (EC50 = 100 nM) and downstream mediators such as STAT5, Crkl and ERK's phosphorylation. In the TEL fused isogenic BaF3 cells, CHMFL-ABL-053 exhibited strong binding ability against BLK, DDR1, DDR2, EPHA8, EphB6, HCK, LCK, p38α and SRC kinases. CHMFL-ABL-053 exhibited an IC50 of 70 nM against ABL1 kinase, inhibited p38α (IC50: 62 nM) and SRC kinase (IC50: 90 nM) by Invitrogen Select Screen biochemical assay. CHMFL-ABL-053 showed less potent to DDR1 (IC50: 292 nM) and DDR2 (IC50: 457 nM). CHMFL-ABL-053 did not exhibit apparent potency against c-KIT kinase (IC50: over 10000 nM). [1]
Pharmacokinetic study showed that CHMFL-ABL-053 had over 4 hours half-life and 24% bioavailability in rats. 50mg/kg/day dosage treatment could almost completely suppress the tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now. [1]
Reference:
1.Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl) benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia.J Med Chem. 2016 Feb 5. [Epub ahead of print]
Cas No. | 1808287-83-3 | SDF | |
化学名 | 2-((3-amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide | ||
Canonical SMILES | CC1=CC=C(NC2=NC(NC)=C(C(NC3=CC(NC(C4=CC=CC(C(F)(F)F)=C4)=O)=CC=C3C)=O)C=N2)C=C1N | ||
分子式 | C28H26F3N7O2 | 分子量 | 549.55 |
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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.8197 mL | 9.0984 mL | 18.1967 mL |
5 mM | 0.3639 mL | 1.8197 mL | 3.6393 mL |
10 mM | 0.182 mL | 0.9098 mL | 1.8197 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 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
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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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