Name: Rebastinib (DCC-2036)
Brand: Selleck Chemicals
SKU: S2634
Availability: InStock
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Batch: S263401 DMSO]111 mg/mL]false]Ethanol]18 mg/mL]false]Water]Insoluble]false Purity: 99.94%

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Datasheet

99.94

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src HIF FLT FLT3 HER2
Other Bcr-Abl Inhibitors	Degrasyn (WP1130) Bafetinib GNF-5 Berbamine GNF-2 Olverembatinib (GZD824) dimesylate PD173955 GNF-7 Radotinib Berbamine dihydrochloride

Solubility

In vitro
Batch:

DMSO : 111 mg/mL (200.5 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 18 mg/mL

Water : Insoluble

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Mass	Concentration	Volume	Molecular Weight
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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.

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Chemical Information, Storage & Stability

Molecular Weight	553.59	Formula	C₃₀H₂₈FN₇O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1020172-07-9	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			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

Mechanism of Action

Features	A conformational control inhibitor of Abl1 and T315I Abl1.
Targets/IC₅₀/Ki	u-Abl1 (native) (Cell-free assay) 0.75 nM Abl1 (H396P) (Cell-free assay) 1.4 nM p-Abl1 (native) (Cell-free assay) 2 nM FLT3 (Cell-free assay) 2 nM p-Abl1 (T315I) (Cell-free assay) 4 nM KDR (Cell-free assay) 4 nM u-Abl1 (T315I) (Cell-free assay) 5 nM Tie-2 (Cell-free assay) 6 nM Lyn (Cell-free assay) 29 nM Src (Cell-free assay) 34 nM FGR (Cell-free assay) 38 nM Hck (Cell-free assay) 40 nM PDGFRα (Cell-free assay) 70 nM
In vitro	Rebastinib (DCC-2036) shows potent inhibitory activities against purified native Abl1 in unphosphorylated (u-Abl1^native) and phosphorylated (p-Abl1^native) forms, unphosphorylated and phosphorylated gatekeeper mutant Abl1^T315I, and the activation loop mutant Abl1^H396P in a non-ATP-competitive manner with IC50 values 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 values of 34 nM, 29 nM, 38 nM, 40 nM, 4 nM, 2 nM and 6 nM, respectively. 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. 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.
Kinase Assay	Assay of Abl1 kinase isoforms and determination of inhibitor potency
Kinase Assay	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 Rebastinib (DCC-2036) 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.
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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/21481795/ [2] https://pubmed.ncbi.nlm.nih.gov/21505103/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03717415	Completed	Locally Advanced or Metastatic Solid Tumor	Deciphera Pharmaceuticals LLC	January 2 2019	Phase 1\|Phase 2
NCT03601897	Completed	Locally Advanced or Metastatic Solid Tumor	Deciphera Pharmaceuticals LLC	October 25 2018	Phase 1\|Phase 2

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Rebastinib (DCC-2036) Bcr-Abl inhibitor

Chemical Structure

Molecular Weight: 553.59