Physicochemical Properties
| Molecular Formula | C32H42N4O5 |
| Molecular Weight | 562.69968 |
| Exact Mass | 462.172 |
| CAS # | 1094067-13-6 |
| Related CAS # | SCH-1473759;1094069-99-4 |
| PubChem CID | 53317913 |
| Appearance | White to yellow solid powder |
| LogP | 3.444 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 31 |
| Complexity | 569 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | YBAZMWNWFHDNTH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H26N8OS.ClH/c1-5-27(20(3,4)12-29)11-15-6-17(30-26-15)25-18-19-21-9-16(14-7-22-23-8-14)28(19)10-13(2)24-18;/h6-10,29H,5,11-12H2,1-4H3,(H,22,23)(H,24,25);1H |
| Chemical Name | 2-[ethyl-[[5-[[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]amino]-1,2-thiazol-3-yl]methyl]amino]-2-methylpropan-1-ol;hydrochloride |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Aurora A and B are directly bound by SCH-1473759, with a Kd of 20 and 30 nM, respectively. Additionally, the Src kinase family (IC50<10 nM), Chk1 (IC50=13 nM), VEGFR2 (IC50=1 nM), and IRAK4 (IC50=37 nM) are all inhibited by SCH-1473759. IC50>1000 nM) against 34 additional kinases from various kinome families reveals no discernible action. With an IC50 of 6 nM, SCH-1473759 suppresses the growth of HCT116 cells[1]. Tumor cell lines from many tissues (breast, ovary, prostate, lung, colon, brain, stomach, kidney, skin, and leukemia) are inhibited by SCH 1473759. With IC50 values less than 5 nM, A2780, LNCap, N87, Molt4, K562, and CCRF-CEM are the most sensitive cell lines [2]. |
| ln Vivo | At day 16, 50% tumor growth inhibition (TGI) was shown by SCH-1473759 at a low dose of 5 mg/kg (ip, bid), which was well tolerated in a continuous dosing regimen. An intermittent schedule of five days on and five days off allowed for good tolerance of the larger dose of 10 mg/kg (ip, bid), which produced a TGI of 69% on day sixteen. With a high clearance in rats and a moderate clearance in dogs and monkeys, SCH-1473759 demonstrated good exposure in all species. There is a high tissue dispersion despite the moderate half-life [1]. In four human tumor xenograft models, SCH 1473759 exhibits dose- and schedule-dependent anticancer efficacy. Furthermore, SCH 1473759 is more effective when used in conjunction with taxanes; it was discovered that the optimal time to take it was 12 hours following taxane treatment [2]. |
| References |
[1]. 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]. 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. |
Solubility Data
| Solubility (In Vitro) |
H2O : ~8.33 mg/mL (~17.99 mM) DMSO : ~7.14 mg/mL (~15.42 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.71 mg/mL (1.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.71 mg/mL (1.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7771 mL | 8.8857 mL | 17.7715 mL | |
| 5 mM | 0.3554 mL | 1.7771 mL | 3.5543 mL | |
| 10 mM | 0.1777 mL | 0.8886 mL | 1.7771 mL |