Rebastinib (DCC-2036)

製品コードS2634 バッチS263401

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C30H28FN7O3
分子量 553.59 CAS No. 1020172-07-9
Solubility (25°C)* 体外 DMSO 111 mg/mL (200.5 mM)
Ethanol 18 mg/mL (32.51 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Rebastinib (DCC-2036) is a conformational control Bcr-Abl inhibitor for Abl1(WT) and Abl1(T315I) with IC50 of 0.8 nM and 4 nM, also inhibits SRC, LYN, FGR, HCK, KDR, FLT3, and Tie-2, and low activity to seen towards c-Kit. Phase 1.
in vitro Rebastinib (DCC-2036) shows potent inhibitory activities against purified native Abl1 in unphosphorylated (u-Abl1native) and phosphorylated (p-Abl1native) forms, unphosphorylated and phosphorylated gatekeeper mutant Abl1T315I, and the activation loop mutant Abl1H396P in a non-ATP-competitive manner with IC50 of 0.8 nM, 2 nM, 1.4 nM, 5 nM, and 4 nM, respectively. Moreover, it also inhibits the Src family kinases Src, LYN, FGR, and HCK, and the receptor TKs KDR, FLT3, and TIE2 with IC50 of 34 nM, 29 nM, 38 nM, 40 nM, 4 nM, 2 nM and 6 nM, respectively. [1] This compound shows anti-proliferative activities against Ba/F3 cells expressing native or mutant Bcr-Abl1 with IC50 ranging from 2 nM to 150 nM. In addition, it also inhibits proliferation of the Ph+ cell line K562 (IC50 5.5 nM), and induces apoptosis in both Bcr-Abl1-expressing Ba/F3 and K562 cells potently. [1] A recent study shows that it exhibits selectivity for growth inhibition of Bcr-Abl-positive cells by its marked inhibition of CML cell lines compared to non-CML leukemia lines. [2]
in vivo In a mouse allograft model bearing Ba/F3-Bcr-Abl1T315I leukemia cells, treatment with Rebastinib (DCC-2036) by oral gavage at 100 mg/kg once daily effectively inhibits Bcr-Abl1 signaling and significantly prolongs mouse survival. [1]
特徴 A conformational control inhibitor of Abl1 and T315I Abl1.

プロトコル(参考用のみ)

キナーゼアッセイ Assay of Abl1 kinase isoforms and determination of inhibitor potency
Activity of u-Abl1native is determined by following the production of ADP from the kinase reaction through coupling with the pyruvate kinase/lactate dehydrogenase system. In this assay, the oxidation of NADH (measured as a decreased A340nm) is continuously monitored spectrophotometrically. The final reaction mixture (100 μL, in a 384-well Corning plate) is prepared as follows: An Abl1 kinase/coupled assay components mixture is prepared containing u-Abl1 kinase (1 nM), Abltide (EAIYAAPFAKKK, 0.2 mM), MgCl2 (9 mM), pyruvate kinase (~ 4 units), lactate dehydrogenase (~ 0.7 units), phosphoenol pyruvate (1 mM), and NADH (0.28 mM) in 90 mM Tris containing 0.1 % octyl-glucoside and 1 % DMSO, pH 7.5. Separately, an inhibitor mixture is prepared containing this compound serially diluted 3-fold in DMSO followed by dilution into buffer composed of 180 mM Tris, pH 7.5, containing MgCl2 (18 mM) and 0.2 % octyl-glucoside. Fifty μL of the inhibitor mixture is mixed with 50 μL of the above Abl1 kinase/coupled assay components mixture, which is then incubated at 30 °C for 2 hours before 2 μL of 25 mM ATP (500 μM, final) is added to start the reaction. The reaction is recorded every 2 minutes for 2.5 hours at 30 °C on a Polarstar Optima or Synergy2 plate reader. Reaction rate (slope) is calculated using the 1 to 2 hour time frame with reader's software. Percent inhibition is obtained by comparison of reaction rate with that of a DMSO control. IC50 values are calculated from a series of percent inhibition values determined at a range of inhibitor concentrations using GraphPad Prism. The kinase assay for Abl1T315I, p-Abl1native or Abl1H396P is assayed the same as above except that 2.2 nM Abl1T315I, 1 nM p-Abl1 native or 1.3 nM Abl1H396P is used. The above assay format is also used for kinases other than Abl1 with the exception of TIE2, for which a fluorescence polarization/Transcreener format is used. The assay conditions are the same as described above except that PolyE4Y (final 1 mg/mL) is used as the substrate and one hour preincubation is used.
細胞アッセイ 細胞株 Ba/F3 cells and primary Ph+ leukemia cells
濃度 0-10 μM
反応時間 72 hours
実験の流れ Ba/F3 cells or primary Ph+ leukemia cells are plated in triplicate in 96-well plates containing test compounds. After 72 hours, viable cells are quantified by Resazurin or MTT assay. Cells are diluted in medium to be added to each well of a 96-well tissue culture-treated plate. All cells are incubated overnight and maintained in a humidified atmosphere at 37 °C and 5% CO2. Cells are treated the following day. Serum-free medium is used during treatment with Rebastinib (DCC-2036). MTT is used to assess the viability of cells following treatment with this compound. Aliquots of 20 mL of stock MTT solution are added to each well containing 200 mL of medium (10% final solution) and incubated with the cells for 2 hours. Following incubation the medium is removed and 200 mL of dimethylsulfoxide added to solubilize the formazan crystals. The absorbance is read on the plate reader at 550 and 690 nm. A subtraction analysis of the dual wavelength is performed (D550 to D690) to increase accuracy of the measurement.
動物実験 動物モデル Ba/F3 cells transformed to interleukin-3 independence by transduction with either Bcr-Abl1native or Bcr-Abl1T315I retrovirus are injected intravenously into syngeneic Balb/c mice.
投薬量 ≤100 mg/kg
投与方法 Administered via p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/21481795/
  • https://pubmed.ncbi.nlm.nih.gov/21505103/

カスタマーフィードバック

Data from [Data independently produced by PLoS One, 2013, 8, e73059]

Data from [PLoS One, 2013, 8, e73059]

Data from [Data independently produced by , , Int J Cancer, 2018, doi:10.1002/ijc.31915]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Enhancing immunotherapy efficacy in colorectal cancer: targeting the FGR-AKT-SP1-DKK1 axis with DCC-2036 (Rebastinib) [ Cell Death Dis, 2025, 16(1):8] PubMed: 39788945
Rebastinib attenuates acute lung injury by promoting NLRP3 ubiquitination and blocking NLRP3/GSDMD signaling pathway in macrophages and protecting alveolar epithelial cells [ Int Immunopharmacol, 2025, 159:114819] PubMed: 40403501
DCC-2036 inhibits osteosarcoma via targeting HCK and the PI3K/AKT-mTORC1 axis to promote autophagy [ World J Surg Oncol, 2025, 23(1):115] PubMed: 40176057
Tet1 safeguards lineage allocation in intestinal stem cells [ bioRxiv, 2025, 2025.05.08.652522] PubMed: 40463069
The molecular basis of Abelson kinase regulation by its αI-helix [ Elife, 2024, 12RP92324] PubMed: 38588001
ErbBs in Lens Cell Fibrosis and Secondary Cataract [ Invest Ophthalmol Vis Sci, 2023, 64(10):6] PubMed: 37418274
ErbBs in Lens Cell Fibrosis and Secondary Cataract [ Invest Ophthalmol Vis Sci, 2023, 64(10):6] PubMed: 37418274
Reengineering Ponatinib to Minimize Cardiovascular Toxicity [ Cancer Res, 2022, 82-15:2777-2791] PubMed: 35763671
Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis [ Cancer Cell, 2021, S1535-6108(21)00383-4] PubMed: 34388376
An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy. [ Nat Cell Biol, 2019, 21(2):203-213] PubMed: 30664786

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。