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Prexasertib dihydrochloride

Cat. No. M9042
Prexasertib dihydrochloride Structure
Synonym:

LY2606368 Prexasertib HCl

Size Price Availability Quantity
5mg USD 105  USD105 In stock
10mg USD 180  USD180 In stock
25mg USD 350  USD350 In stock
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Quality Control
Biological Activity

Prexasertib (LY2606368) is a substrate ATP competitively selective inhibitor of CHK1 and CHK2 with IC50 values of <1 nM and 8 nM against CHK1 and CHK2, respectively. LY2606368 treatment led to TUNEL and pH2AXy positive double-stranded DNA breaks in cells in S phase. LY2606368 effectively cancelled the G2-M checkpoint activated by Doxorubicin in P53-deficient HeLa cells with EC50 of 9 nM. LY2606368 can play an antiproliferative role in a wide range of cells, with IC50s < 50 nM in most sensitive cell lines. Only a few cell lines were resistant to LY2606368, IC50s > 1000 nM.

In vivo studies, LY2606368 can effectively inhibit tumor growth in tumor xenograft model and exert anti-tumor activity. In the SKOV3 ovarian cancer model, LY2606368 inhibited the growth of primary tumor and significantly reduced the rate of metastasis and ascites accumulation. In SW1990 model of pancreatic carcinoma in situ, LY2606368 inhibited the growth of 92% of the primary tumor and prevented its metastasis to lymph node tuberculosis, spleen and intestine.


Protocol
Cell Experiment
Cell lines HeLa cells
Preparation method HeLa cells were plated onto T25 flasks and allowed to recover for 24 hours. LY2606368 was then added to give final concentrations of 33 or 100 nmol/L. In some experiments, 20μmol/L Z-VAD-FMK was included during the drug treatment. Cells were treated for 12 hours, and during the last 2 hours, colchicine was added to 1 μg/mL. Fixation of nuclei for metaphase spreads was done following the method of Bayani and Squire. Chromosome spreads were done. A 12-μL volume of cell suspension in 3:1 methanol/acetic acid fixative was dropped from a height of 3 cm onto dry glass slides or coverslips. The slides were then heated for 45 seconds on a 43°C metal block, before being removed to allow drying to complete at room temperature. Coverslips were mounted on slides with Vectashield Hard Set mounting medium with DAPI. Slides were examined with a Leica DMR fluorescence microscope and images were captured using a SPOT RT3 Slider camera.
Concentrations 33 or 100 nmol/L
Incubation time 12 h
Animal Experiment
Animal models Female CD-1 nu-/nu- mice
Formulation 20% Captisol, pH4
Dosages 15 mg/kg
Administration s.c.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 438.31
Formula C18H19N7O2.2HCl
CAS Number 1234015-54-3
Purity >99%
Solubility DMSO 2 mg/mL
Storage at -20°C
References

[1] Yin Y, et al. Am J Cancer Res. Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer.

[2] Hong D, et al. J Clin Oncol. Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With Advanced Cancer.

[3] King C, et al. Mol Cancer Ther. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms.

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Keywords: Prexasertib dihydrochloride, LY2606368 Prexasertib HCl supplier, Checkpoint, inhibitors

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