Prexasertib dihydrochloride

Research use only, not for human use.

A potent, selective, ATP-competitive inhibitor of CHK1 with Ki of 0.9 nM.

A potent, selective, ATP-competitive inhibitor of CHK1 with Ki of 0.9 nM; potently abrogates the G2-M checkpoint activated by doxorubicin in p53-deficient HeLa cells with EC50 of 9 nM; causes replication catastrophe in vitro and in vivo; shows significant tumor growth inhibition in xenograft tumor models.Lung Cancer Phase 2 Clinical.

Cell Cycle AnalysisCell Line:HeLa cells Concentration:33, 100 nM.Incubation Time:For 7 hours Result:Had an IC50 of 37 nM and resulted in the G2-M population received DNA damage during S-phase but continued to progress through the cell cycle into an early mitosis.Western Blot Analysis Cell Line:HT-29 cells.Concentration:8, 16, 31, 63, 125, 250 nM.Incubation Time:Pre-treated for 15 minutes Result:Inhibited CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) (IC50 of less than 31 nM) in HT-29 cells.

Animal Model:Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cellsDosage:1, 3.3, or 10 mg/kg Administration:SC; twice daily for 3 days, rest 4 days; for three cyclesResult:Caused statistically significant tumor growth inhibition (up to 72.3%).Animal Model:Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells Dosage:15 mg/kg (Pharmacokinetic Analysis) Administration:SC (200 μL) Result:CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures. Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage.

LY-2606368 dihydrochloride | LY 2606368 dihydrochloride

Angiogenesis

Chk

Chk1|Chk2|RSK

Cancer

Lung Cancer

1234015-54-3

438.311

C18H21Cl2N7O2

>98% (HPLC)

DMSO: ≥ 32 mg/mL

COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N.Cl.Cl

2-Pyrazinecarbonitrile, 5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]-, hydrochloride (1:2)

(-20℃)

With Ice Pack

≥ 2 years