DCC-2036 (Rebastinib)
(Synonyms: N-[3-叔丁基-1-(喹啉-6-基)-1H-吡唑-5-基]-N'-[2-氟-4-[(2-(甲基氨基甲酰基)吡啶-4-基)氧]苯基]脲,DCC-2036) 目录号 : GC14007
An orally bioavailable tyrosine kinase inhibitor
Cas No.:1020172-07-9
Sample solution is provided at 25 µL, 10mM.
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DCC-2036 is a conformational control inhibitor of ABL1 with IC50 value of 0.8nM [1].
DCC-2036 is synthesized as a dual-anchoring inhibitor that binds both the switch control pocket E282/R386 pair and the Met318 ATP hinge. It shows a IC50 value of 0.8nM. DCC-2036 also exerts potent inhibition of the gatekeeper mutant ABL1T315I with IC50 value of 4nM. DCC-2036 inhibits ABL1 through forcing the kinase domains into inhibitor-bound, inactive Type II conformations. For the purified ABL1, DCC-2036 strongly inhibits unphosphorylated native ABL1, phosphorylated native ABL1, ABL1H396P, unphosphorylated ABL1T315I and phosphorylated ABL1T315I with IC50 values of 0.82nM, 2nM, 1.4nM, 5nM and 4nM, respectively. It is found that DCC-2036 inhibits ABL1 in a non-ATP-competitive manner. In cellular assay, DCC-2036 inhibits the proliferation of Ba/F3 and K562 cells with IC50 values of 5.4nM and 5.5nM, respectively. Moreover, treatment of DCC-2036 can effectively prolong survival in mice bearing Ba/F3-BCR-ABL1T315I leukemia cells. DCC-2036 is also capable to inhibit BCR-ABL1 in primary leukemic cells from patients with Ph+ leukemia [1].
References:
[1] Chan W W, Wise S C, Kaufman M D, et al. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer cell, 2011, 19(4): 556-568.
| Cell experiment [1]: | |
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Cell lines |
Ba/F3 cells expressing native or mutant BCRABL1 |
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Preparation method |
The solubility of this compound in DMSO is > 27.7 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
2 ~ 150 nM |
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Applications |
In Ba/F3 cells expressing native BCR-ABL1native, DCC-2036 effectively inhibited cell proliferation with an IC50 value of 5.4 nM. DCC-2036 also potently inhibited Ba/F3 cells expressing BCR-ABL1 mutants that were resistant to Imatinib, Dasatinib (T315A) and Nilotinib (L248R, Y253H, E255V and F359C). In addition, DCC-2036 was effective on the gatekeeper mutant BCR-ABL1T315I (IC50 = 13 nM), on which all three FDA-approved TKIs were ineffective. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing Ba/F3-BCR-ABL1T315I leukemia cells |
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Dosage form |
100 mg/kg; p.o. |
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Applications |
In mice bearing Ba/F3-BCR-ABL1T315I leukemia cells, a single oral dose of DCC-2036 at 100 mg/kg resulted in a plasma concentration over 12 μM for up to 24 hrs, and effectively inhibited BCR-ABL1 signaling for up to 8 hrs. Treating mice bearing Ba/F3-BCR-ABL1 T315I leukemia cells with DCC-2036 at the dose of 100 mg/kg once daily significantly prolonged their survival. |
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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]. Chan W W, Wise S C, Kaufman M D, et al. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer cell, 2011, 19(4): 556-568. | |
| Cas No. | 1020172-07-9 | SDF | |
| 别名 | N-[3-叔丁基-1-(喹啉-6-基)-1H-吡唑-5-基]-N'-[2-氟-4-[(2-(甲基氨基甲酰基)吡啶-4-基)氧]苯基]脲,DCC-2036 | ||
| 化学名 | 4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide | ||
| Canonical SMILES | CC(C)(C)C1=NN(C(=C1)NC(=O)NC2=C(C=C(C=C2)OC3=CC(=NC=C3)C(=O)NC)F)C4=CC5=C(C=C4)N=CC=C5 | ||
| 分子式 | C30H28FN7O3 | 分子量 | 553.59 |
| 溶解度 | ≥ 27.7mg/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 | 1.8064 mL | 9.032 mL | 18.0639 mL |
| 5 mM | 0.3613 mL | 1.8064 mL | 3.6128 mL |
| 10 mM | 0.1806 mL | 0.9032 mL | 1.8064 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