DCC-2036 (Rebastinib) (Synonyms: DCC-2036) |
| Catalog No.GC14007 |
DCC-2036(레바스티닙)(DCC-2036)은 각각 0.8nM 및 4nM의 IC50을 갖는 Abl1WT 및 Ab11T315I에 대한 경구 활성, 비-ATP-경쟁적Bcr-Abl 억제제입니다. DCC-2036(Rebastinib)은 또한 SRC, KDR, FLT3 및 Tie-2를 억제하며 c-Kit에 대해 낮은 활성을 보입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1020172-07-9
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
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]: | |
|
Cell lines |
Ba/F3 cells expressing native or mutant BCRABL1 |
|
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. |
|
Reacting condition |
2 ~ 150 nM |
|
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]: | |
|
Animal models |
Mice bearing Ba/F3-BCR-ABL1T315I leukemia cells |
|
Dosage form |
100 mg/kg; p.o. |
|
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. |
|
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. |
|
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 | |
| Synonyms | DCC-2036 | ||
| Chemical Name | 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 | ||
| Formula | C30H28FN7O3 | M.Wt | 553.59 |
| Solubility | ≥ 27.7mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *