Ilorasertib

SKU: orb1296236

Description

Ilorasertib

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 1227939-82-3
• MW: 488.54
• Purity: 98.03%
• Formula: C₂₅H₂₁FN₆O₂S
• SMILES: NC1=C2C(=C(C=N1)C3=CN(CCO)N=C3)SC=C2C4=CC=C(NC(NC5=CC(F)=CC=C5)=O)C=C4
• Target: FLT,VEGFR,c-RET,PDGFR,Aurora Kinase
• Solubility: DMSO:55 mg/mL (112.58 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.09 mM)

Bioactivity

• Target IC50:
  CSF1R:3 nM|VEGFR3:43 nM|VEGFR1:1 nM|VEGFR2:2 nM|c-Kit:20 nM|Aurora A:120 nM|Aurora C:1 nM|Aurora B (Y156H):12 nM|Aurora B:7 nM|FLT3:1 nM|PDGFRα:11 nM|PDGFRβ:13 nM
• In Vivo:
  Ilorasertib inhibits the VEGF response with a potency (ED50: 0.2 mg/kg, i.v.) in a uterine edema model. 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 (20 mg/kg, p.o.) inhibits the growth of established tumors and causes regression of advanced tumors in human xenograft models . Ilorasertib demonstrates significant antitumor efficacy in both solid and hematological xenograft models after intravenous, mini-pump or parenteral once-weekly dosing .
• In Vitro:
  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 (EC50: 5, 10 nM). Ilorasertib shows antiproliferative activity against BCR-ABL expressing CML cells and cells expressing the Gleevec-resistant BCR-ABL T315I mutation (IC50: 47, 260 nM) .
• Cell Research:
  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 Research:
  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 cm^3 or 0.5 cm^3. 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 cm^3. 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). The dosing volume is 10 mL/kg .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PDGFRβ, RET, Vascular endothelial growth factor receptor, VEGFR2, VEGFR1, VEGFR, VEGFR3, PDGFR, Platelet-derived growth factor receptor, Ilorasertib, inhibit, Inhibitor, histone H3 phosphorylation, MDS, H1299, H460 cells, FLT1, AML, anti-tumor, antiproliferative activity, AuroraKinase, Aurora C, Aurora Kinase, Aurora B, Aurora A, ABT348, ABT-348, ABT 348, cRET

Compound Identifiers

PubChem CID

46207586