Tozasertib

SKU: orb1305377

Description

Tozasertib

Research Area

Cell Biology

Key Properties

• CAS Number: 639089-54-6
• MW: 464.59
• Purity: >98%
• Formula: C₂₃H₂₈N₈OS
• SMILES: CN1CCN(CC1)c1cc(Nc2cc(C)[nH]n2)nc(Sc2ccc(NC(=O)C3CC3)cc2)n1
• Target: Kinase
• Solubility: Soluble in DMSO (up to 100 mg/ml).

Bioactivity

• Target IC50:
  Aurora B:18 nM (Ki)|Aurora A:0.6 nM (Ki)|Aurora C:4.6 nM (Ki)
• In Vivo:
  In nude mice treated with Tozasertib at 75 mg/kg, twice a day intraperitoneally (b.i.d. i.p.) for 13 d, mean tumor volumes were reduced by 98% in comparison with the control group. In four of ten animals, the final tumor volume was lower than the initial volume before treatment. Tumor growth reduction was dose-dependent and significant at a dose of 12.5 mg/kg b.i.d. Tozasertib was well tolerated, with a small decrease in body weight observed only at the highest dose (5% decrease at 75 mg/kg b.i.d.). Tozasertib also induced tumor regression in pancreatic and colon xenograft models. In an established human pancreatic (MIA PaCa-2) xenograft model, Tozasertib at 50 mg/kg b.i.d i.p. induced regression in seven of ten tumors, with a 22% decrease in mean tumor volume relative to initial tumor size before treatment .
• In Vitro:
  Tozasertib (VX-680) is a potent inhibitor of all three Aurora kinases, with apparent inhibition constant (Ki(app)) values of 0.6, 18 and 4.6 nM for Aurora-A, Aurora-B, and Aurora-C, respectively. VX-680 caused accumulation of cells with 4N DNA content and potently inhibited the proliferation of a wide variety of tumor cell types with IC50 values ranging from 15 to 113 nM . Treatment of the different ATC cells with VX-680 inhibited proliferation in a time- and dose-dependent manner, with the IC50 between 25 and 150 nM. The VX-680 significantly impaired the ability of the different cell lines to form colonies in soft agar. Analysis of caspase-3 activity showed that VX-680 induced apoptosis in the different cell lines .
• Cell Research:
  Logarithmically growing MCF-7 cells were incubated with either VX-680 or DMSO for 48 h. Single-cell suspensions were fixed in 70% ethanol for 15 min, incubated with RNase (1 mg/ml) at 37 °C for 30 min, labeled with 400 μl propidium iodide (50 μg/ml) for at least 15 min at room temperature. Cell-cycle profiles were determined by flow cytometric analysis .
• Animal Research:
  For the HL-60 study, female athymic NCr-nu mice were inoculated subcutaneously with 10^7 HL-60(TB) leukemia cells into the right axillary area. Treatment was administered i.p. b.i.d. after tumors reached 150–200 mm^3. VX-680 was prepared in a vehicle of 50% PEG 300 in 50 mM phosphate buffer. Cisplatin, formulated in saline, was administered i.p. q.4.d. for a total of three injections, at a dose of 5.4 mg/kg. For the MIA PaCa-2 studies, female MF1 nude mice were inoculated with 10^7 MIA PaCa-2 cells into the dorsal flank. Treatment was administered i.p. b.i.d. after tumors reached 175 mm^3. VX-680 was prepared in a vehicle of 50% PEG 300 in 50 mM phosphate buffer. 5-fluorouracil, formulated in saline, was administered i.v. q.4.d. at a dose of 50 mg/kg. For the HCT116 study, female Hsd RH rnu/nu rats were inoculated with 10^7 HCT116 cells into the right flank. Treatment was administered once the tumors reached 700–950mm^3. VX-680 was administered continuously through an indwelling femoral catheter, followed by a saline infusion for 4 d before repeating the dose cycle. For all studies, tumor volume was determined by caliper measurements three times a week .

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

VX-680; MK-0457

Compound Identifiers

PubChem CID

5494449