DCC-2618
(Synonyms: DCC2618;DCC 2618) 目录号 : GC11171
A dual inhibitor of c-Kit and c-MET
Cas No.:1225278-16-9
Sample solution is provided at 25 µL, 10mM.
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IC50: 6 nM, 9 nM, 18 nM, 5 nM, 14 nM and 9 nM for wt c-KIT, KIT V654A, KIT T670I, KIT D816H, KIT D816V and KIT JMD ΔVV/D816V, respectively.
DCC-2618 is a small-molecule inhibitor of KIT kinases.
Gastrointestinal stromal tumors (GIST) are driven by gain-of-function mutations of the KIT (approx 90%) or PDGFR (approx 10%) receptor tyrosine kinases. DCC-2618 has been designed to effectively inhibit the imatinib and sunitinib-sensitive KIT juxtamenbrane domin mutants as well as secondary resistant KIT iniase-domain mutants.
In vitro: DCC-2618 is a kinase switch inhibitor that can control drug resistant mutants of KIT and PDGFR in GIST. DCC-2618 acts by imposing an inactive conformation (shape) of highly resistant and aggressive secondary mutations of KIT kinase [1].
In vivo: DCC-2618 inhibits KIT in GIST tumor xenografts after single dose. At the doses of 50 and 25 mpk, DCC-2618 showed promising potency on pKIT (Y703) with the inhibition ranging from 39% to 79% 2-12 hrs after the administration [1].
Clinical trial: A Phase I trial with refractory GIST patients is planned.
Reference:
[1] DCC-2618, a small molecule inhibitor of normal and mutant KIT kinasefor treatment of refractory gastrointestinal stromal tumors (GIST)Deciphera Pharmaceuticals, Lawrence, KS.
| Cell experiment [1]: | |
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Cell lines |
CHO and GIST cells |
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Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
43 ~ 106 nM for CHO cells, 2 ~ 32 nM for GIST cells |
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Applications |
In CHO cells, DCC-2618 inhibited resistant Exon 17 KIT mutations with the IC50 values ranging from 43 to 106 nM. In GIST cells, DCC-2618 inhibited mutant KIT with the IC50 values ranging from 2 to 32 nM. |
| Animal experiment [1]: | |
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Animal models |
GIST xenografts |
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Dosage form |
25 and 50 mg/kg; p.o. |
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Applications |
DCC-2618 inhibited KIT in GIST xenografts after single dose. At the doses of 25 and 50 mg/kg, DCC-2618 showed promising potency on pKIT (Y703) with the inhibition ranging from 39% to 79% 2 ~ 12 hrs after the administration. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. DCC-2618, a small molecule inhibitor of normal and mutant KIT kinasefor treatment of refractory gastrointestinal stromal tumors (GIST)Deciphera Pharmaceuticals, Lawrence, KS. | |
| Cas No. | 1225278-16-9 | SDF | |
| 别名 | DCC2618;DCC 2618 | ||
| 化学名 | 1-N'-[2,5-difluoro-4-[2-(1-methylpyrazol-4-yl)pyridin-4-yl]oxyphenyl]-1-N-phenylcyclopropane-1,1-dicarboxamide | ||
| Canonical SMILES | CN1C=C(C=N1)C2=NC=CC(=C2)OC3=C(C=C(C(=C3)F)NC(=O)C4(CC4)C(=O)NC5=CC=CC=C5)F | ||
| 分子式 | C26H21F2N5O3 | 分子量 | 489.47 |
| 溶解度 | >179.2mg/mL 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 | 2.043 mL | 10.2151 mL | 20.4303 mL |
| 5 mM | 0.4086 mL | 2.043 mL | 4.0861 mL |
| 10 mM | 0.2043 mL | 1.0215 mL | 2.043 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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet