Prexasertib dihydrochloride salt form · dihydrochloride · Parent LY2606368
Prexasertib dihydrochloride, LY2606368, is a selective, ATP-competitive second-generation checkpoint kinase 1 inhibitor.
For research use only. Not for human or veterinary use.
Description
Prexasertib dihydrochloride, LY2606368, is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a Ki of 0.9 nM and an IC50 of <1 nM. Prexasertib dihydrochloride inhibits CHK2 (IC50=8 nM) and RSK1 (IC50=9 nM). Prexasertib dihydrochloride causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dihydrochloride shows potent anti-tumor activity.
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.
Identifiers
- SMILES
-
NCCCOC(C=CC=C1OC)=C1C2=CC(NC3=NC=C(C#N)N=C3)=NN2.[H]Cl.[H]Cl - InChIKey
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KMEIPKXRCJTZBZ-UHFFFAOYSA-N
Specifications
- MW (average)
- 438.3110
- Formula
- C18H21Cl2N7O2
- CAS No.
- 1234015-54-3
- Physical state
- Solid
- Color
- Light yellow to yellow
- Shipping
- Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
- Storage
- Powder 4°C, sealed storage, away from moisture; In solvent -20℃ 1 month;
Solubility
Soluble in DMSO H2O
- In vitro
- DMSO 8 mg/mL H2O < 0.1 mg/mL