Ilorasertib (ABT-348) (Synonyms: ABT-348) |
| Catalog No.GC34159 |
Ilorasertib (ABT-348) (ABT-348) is a potent, orally active and ATP-competitive aurora inhibitor with IC50s of116, 5, 1 nM for aurora A, aurora B, aurora C, respectively. Ilorasertib (ABT-348) also is a potent VEGF, PDGF inhibitor. Ilorasertib (ABT-348) has the potential for the research of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1227939-82-3
Sample solution is provided at 25 µL, 10mM.
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Ilorasertib (ABT-348) is an ATP-competitive multitargeted kinase inhibitor with IC50s for inhibiting binding Aurora B (7 nM), C (1 nM), and A (120 nM), and also inhibits RET tyrosine kinase, PDGFRβ, and Flt1 with IC50s of 7 nM, 3 nM and 32 nM.
Ilorasertib is an ATP-competitive multitargeted kinase inhibitor with IC50 for inhibiting cellular autophosphorylation of Aurora B (13 nM), C (13 nM), and A (189 nM). In addition to targeting Aurora kinases, Ilorasertib is a potent inhibitor of the VEGFR and PDGFR kinase families and, to a lesser extent, the Src family of cytoplasmic tyrosine kinases. Ilorasertib induces a concentration-dependent increase in the extent and number of two NSCLC cell lines exhibiting polyploidy. The potency for inducing this response (EC50 = 5 and 10 nM). Ilorasertib shows antiproliferative activity against BCR-ABL expressing CML cells and cells expressing the gleevec-resistant BCR-ABL T315I mutation (IC50 = 47 and 260 nM)[2].
Ilorasertib (25 mg/kg, s.c.) leads to an inhibition of histone H3 phosphorylation in circulating tumor cells obtained from an engrafted leukemia model. Ilorasertib inhibits the VEGF response with a potency (ED50 = 0.2 mg/kg i.v.) in a uterine edema model. Ilorasertib (20 mg/kg, p.o.) inhibits the growth of established tumors and causes regression of advanced tumors in human xenograft models[2]. Ilorasertib demonstrates significant antitumor efficacy in both solid and hematological xenograft models after intravenous, mini-pump or parenteral once-weekly dosing[3].
[1]. Gao C, et al. Characterization of interactions and pharmacophore development for DFG-out inhibitors to RET tyrosine kinase. J Mol Model. 2015 Jul;21(7):167. [2]. Glaser KB, et al. Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27. [3]. Curtin ML, et al. Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families. Bioorg Med Chem Lett. 2012 May 1;22(9):3208-12.
Cell experiment: | Carcinoma cells (2500 cells/well) are plated overnight in full-growth medium (containing 10% FBS). Compound is added to the cells in full-growth medium and incubated for 72 h at 37°C in a CO2 incubator. For leukemia cells, generally 50,000 cells/well are plated in full-growth medium, drug is added, and they are incubated for 72 h. The effects on proliferation are determined by the addition of alamarBlue (final solution 10%), incubation for 4 h, and analysis in a fluorescence plate reader (excitation 544; emission 590), or alternatively, medium is removed and replaced with 200 μL of Cell TiterGlo reagent and analyzed for luminescence. Noncycling primary HUVEC are used to assess the effect of Ilorasertib on nonproliferating cells. Cells (35,000/well) are seeded in growth medium in a 96-well tissue culture plate, and after 2 days, the medium is changed and the cells are treated with Ilorasertib. After an additional 3 days, cell viability is measured with Cell TiterGlo reagent. |
Animal experiment: | sup>[2]For flank xenograft models, cells are suspended in PBS, mixed with Matrigel (phenol red free) in a ratio of 1:4 (v/v), and inoculated into the flank of female SCID/beige mice (5 million cells per site). Inoculated mice are randomized into groups of 10, and treatment is initiated when mean tumor volume is approximately 0.4 cm3 or 0.5 cm3. Tumor growth in the flank is assessed by measuring tumor size with calipers and calculating volume using the formula (L × W2/2). Study groups are terminated before tumor volume reaches 3 cm3. Inhibition of tumor growth is assessed at the time the vehicle-treated group is terminated by calculating the ratio of the mean volume of the test drug group to the mean volume of the untreated (control) group (T/C) and calculating the percentage of inhibition of control [(1 − T/C) × 100]. The dosing formulation of test agents is prepared by stepwise addition, with mixing, of the following reagents: EtOH, Tween 80, polyethylene glycol 400, and 2% hydroxypropyl methylcellulose (2:5:20:73, v/v). Dosing volume is 10 mL/kg. |
References: [1]. Gao C, et al. Characterization of interactions and pharmacophore development for DFG-out inhibitors to RET tyrosine kinase. J Mol Model. 2015 Jul;21(7):167. | |
| Cas No. | 1227939-82-3 | SDF | |
| Synonyms | ABT-348 | ||
| Canonical SMILES | O=C(NC1=CC=CC(F)=C1)NC2=CC=C(C3=CSC4=C3C(N)=NC=C4C5=CN(CCO)N=C5)C=C2 | ||
| Formula | C25H21FN6O2S | M.Wt | 488.54 |
| Solubility | DMSO : 83.33 mg/mL (170.57 mM);Water : < 0.1 mg/mL (insoluble) | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0469 mL | 10.2346 mL | 20.4692 mL |
| 5 mM | 0.4094 mL | 2.0469 mL | 4.0938 mL |
| 10 mM | 0.2047 mL | 1.0235 mL | 2.0469 mL |
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- Purity: >98.00%
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