[CAS NO. 1094067-13-6] SCH-1473759 hydrochloride
PRODUCTS SPECIFICATIONS [1094067-13-6]
DESCRIPTION [1094067-13-6]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 463.00 |
| Molecular Formula | C20H27ClN8OS |
| SMILES | [H]Cl.CC1=CN2C(C(NC3=CC(CN(C(C)(CO)C)CC)=NS3)=N1)=NC=C2C4=CNN=C4 |
Summary
SCH-1473759 hydrochloride is an aurora inhibitor with IC 50 s of 4 and 13 nM for aurora A and B, respectively.
IC50 & Target
|
Aurora A 4 nM (IC 50 ) |
Aurora B 13 nM (IC 50 ) |
In Vitro
SCH-1473759 directly binds to aurora A and B with K d s of 20 and 30 nM, respectively. SCH-1473759 also inhibits the Src family of kinases (IC 50 <10 nM), Chk1 (IC 50 =13 nM), VEGFR2 (IC 50 =1 nM), and IRAK4 (IC 50 =37 nM). It does not have significant activity (IC 50 >1000 nM) against 34 other kinases representing different families of the kinome. SCH-1473759 inhibits HCT116 cells proliferation with an IC 50 of 6 nM [1] . SCH 1473759 inhibits tumor cell lines from different tissues (breast, ovarian, prostate, lung, colon, brain, gastric, renal, skin, and leukemia). The most sensitive cell lines includ A2780, LNCap, N87, Molt4, K562, and CCRF-CEM with IC 50 values <5 nM [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
SCH-1473759 at a low dose of 5 mg/kg (ip, bid) is well-tolerated in a continuous dosing schedule and shows 50% tumor growth inhibition(TGI) on day 16. A higher dose of 10mg/kg(ip, bid) is well-tolerated in an intermittent schedule (5 days on, 5 days off) and gave 69% TGI on day 16. SCH-1473759 shows good exposure in all species with the clearance being high in rodents and moderate in dog and monkey. The half-life is also moderate, but the tissue distribution is high [1] . SCH 1473759 dose- and schedule-dependent anti-tumor activity in four human tumor xenograft models. Further, the efficacy is enhanced in combination with taxanes and found to be most efficacious when SCH 1473759 is dosed 12-h post-taxane treatment [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
H 2 O : 8.33 mg/mL ( 17.99 mM ; ultrasonic and warming and heat to 60°C)
DMSO : 7.14 mg/mL ( 15.42 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1598 mL | 10.7991 mL | 21.5983 mL |
| 5 mM | 0.4320 mL | 2.1598 mL | 4.3197 mL |
| 10 mM | 0.2160 mL | 1.0799 mL | 2.1598 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 0.71 mg/mL (1.53 mM); Clear solution
References
- [1] Yu T, et al. Discovery of a Potent, Injectable Inhibitor of Aurora Kinases Based on the Imidazo-[1,2-a]-Pyrazine Core. ACS Med Chem Lett. 2010 Jun 7;1(5):214-8.
- [2] Basso AD, et al. SCH 1473759, a novel Aurora inhibitor, demonstrates enhanced anti-tumor activity in combination with taxanes and KSP inhibitors. Cancer Chemother Pharmacol. 2011 Oct;68(4):923-33.
