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DCC-2036 (Rebastinib) (Synonyms: DCC-2036)

Katalog-Nr.GC14007

DCC-2036 (Rebastinib) (DCC-2036) ist ein oral aktiver, nicht ATP-kompetitiver Bcr-Abl-Inhibitor fÜr Abl1WT und Abl1T315I mit IC50-Werten von 0,8 nM bzw. 4 nM. DCC-2036 (Rebastinib) hemmt auch SRC, KDR, FLT3 und Tie-2 und hat eine geringe AktivitÄt gegenÜber c-Kit.

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DCC-2036 (Rebastinib) Chemische Struktur

Cas No.: 1020172-07-9

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

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.

Background

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.

Chemical Properties

Cas No. 1020172-07-9 SDF
Überlieferungen 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
Löslichkeit ≥ 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.

Complete Stock Solution Preparation Table

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
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Average Rating: 5 ★★★★★ (Based on Reviews and 22 reference(s) in Google Scholar.)

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