| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SCH-1473759 hydrochloride directly binds to Aurora A and Aurora B with Kd values of 20 and 30 nM, respectively. It also inhibits Src kinase family members (IC₅0 <10 nM), Chk1 (IC₅0 = 13 nM), VEGFR2 (IC₅0 = 1 nM), and IRAK4 (IC₅0 = 37 nM). The compound shows no significant activity against 34 other kinases from various families (IC₅0 >1000 nM).
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| 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].
In vitro, SCH-1473759 hydrochloride inhibits the growth of HCT116 cells with an IC₅0 of 6 nM. It suppresses proliferation of tumor cell lines from multiple tissues including breast, ovarian, prostate, lung, colon, brain, stomach, kidney, skin, and leukemia. A2780, LNCap, N87, Molt4, K562, and CCRF-CEM are among the most sensitive cell lines with IC₅0 values less than 5 nM. Asynchronous cells require 24-hour exposure for maximal induction of >4N DNA content. |
| 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].
In vivo, SCH-1473759 hydrochloride demonstrates dose- and schedule-dependent antitumor efficacy in four human tumor xenograft models. At 5 mg/kg (i.p., bid) in a continuous dosing schedule, it produces 50% tumor growth inhibition (TGI) at day 16. An intermittent schedule (5 days on, 5 days off) allows toleration of higher doses (10 mg/kg, i.p., bid), yielding 69% TGI at day 16. The compound shows enhanced efficacy when combined with taxanes. |
| Enzyme Assay |
In vitro enzyme binding assays for SCH-1473759 hydrochloride utilize purified recombinant Aurora A and B kinases. The compound is incubated with the kinases and a peptide substrate in the presence of ATP. Kinase activity is measured by detecting phosphorylated substrate via luminescence-based or fluorescence-based methods. IC₅0 values are determined from dose-response curves.
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| Cell Assay |
Cellular assays are performed using asynchronous human cancer cell lines (e.g., HCT116, A2780) cultured in appropriate media. Cells are treated with serial dilutions of SCH-1473759 hydrochloride (0.1-1000 nM) for 24-72 hours. Cell growth inhibition is assessed using ATP-based viability assays (CellTiter-Glo). Cell cycle analysis is performed by propidium iodide staining followed by flow cytometry to measure >4N DNA content.
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| Animal Protocol |
In vivo efficacy studies are conducted in immunocompromised mice bearing subcutaneous human tumor xenografts. SCH-1473759 hydrochloride is administered intraperitoneally at doses of 5-10 mg/kg, either daily (bid) or on intermittent schedules (5 days on, 5 days off). Tumor volume is measured twice weekly, and TGI is calculated. Pharmacodynamic markers such as phospho-histone H3 inhibition are assessed in tumor tissues.
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| ADME/Pharmacokinetics |
SCH-1473759 hydrochloride exhibits high clearance in rats, moderate clearance in dogs and monkeys, and demonstrates good exposure across all species. It has moderate half-life with high tissue distribution. The compound shows favorable intrinsic aqueous solubility (11.4 mM), which supports formulation for in vivo administration. Oral bioavailability data are limited; parenteral administration is used in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicological data for SCH-1473759 hydrochloride indicate that the compound is well-tolerated at efficacious doses. In animal studies, continuous dosing at 5 mg/kg (i.p., bid) is well-tolerated, while higher doses (10 mg/kg) require intermittent scheduling. No severe adverse effects have been reported at therapeutic doses. Standard toxicity evaluations include monitoring of body weight, clinical signs, and hematological parameters.
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| References |
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| Additional Infomation |
SCH-1473759 hydrochloride is a research-use compound not approved for clinical therapeutic applications. It is a valuable tool for studying Aurora kinase biology and the role of mitotic regulators in cancer. The compound's multi-target profile provides insights into combination strategies with taxanes. It is used in preclinical oncology research to investigate mechanisms of cell cycle disruption and antitumor efficacy.
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| Molecular Formula |
C32H42N4O5
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|---|---|
| Molecular Weight |
562.69968
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| Exact Mass |
462.172
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| CAS # |
1094067-13-6
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| Related CAS # |
SCH-1473759;1094069-99-4
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| PubChem CID |
53317913
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| Appearance |
White to yellow solid powder
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| LogP |
3.444
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
569
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN(CC1=NSC(=C1)NC2=NC(=CN3C2=NC=C3C4=CNN=C4)C)C(C)(C)CO.Cl
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| InChi Key |
YBAZMWNWFHDNTH-UHFFFAOYSA-N
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| 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
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| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
H2O : ~8.33 mg/mL (~17.99 mM)
DMSO : ~7.14 mg/mL (~15.42 mM) |
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| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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