WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H202651
CAS#: 1057249-41-8 (free base)
Description: SNS-314 is a synthetic small molecule Aurora kinase (AK) inhibitor with potential antineoplastic activity. Aurora kinase inhibitor SNS-314 selectively binds to and inhibits AKs A and B, which may result in the inhibition of cellular division and proliferation in tumor cells that overexpress AKs. AKs are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis.
Hodoodo Cat#: H202651
Name: SNS-314
CAS#: 1057249-41-8 (free base)
Chemical Formula: C18H15ClN6OS2
Exact Mass: 430.04
Molecular Weight: 430.930
Elemental Analysis: C, 50.17; H, 3.51; Cl, 8.23; N, 19.50; O, 3.71; S, 14.88.
Related CAS #: 1057249-41-8 (free base) 1146618-41-8 (mesylate)
Synonym: SNS314; SNS-314; SNS 314; SNS-314 free base;
IUPAC/Chemical Name: N-(3-Chlorophenyl)-N'-[5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-2-thiazolyl]urea.
InChi Key: FAYAUAZLLLJJGH-UHFFFAOYSA-N
InChi Code: InChI=1S/C18H15ClN6OS2/c19-11-2-1-3-12(8-11)24-17(26)25-18-21-9-13(28-18)4-6-20-16-15-14(5-7-27-15)22-10-23-16/h1-3,5,7-10H,4,6H2,(H,20,22,23)(H2,21,24,25,26)
SMILES Code: O=C(NC1=NC=C(CCNC2=C3C(C=CS3)=NC=N2)S1)NC4=CC=CC(Cl)=C4
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: 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 Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Related CAS# 1057249-41-8 ( SNS-314 free base) 1146618-41-8 ( SNS-314 mesylate).
| Biological target: | SNS-314 mesylate is an aurora kinase inhibitor with IC50s of 9, 31, and 6 nM for aurora A, B and C, respectively. |
| In vitro activity: | The effects of SNS-314 mesylate were assessed on the ATC (anaplastic thyroid carcinoma) derived cell lines CAL-62, 8305C, 8505C and BHT-101 by means of cell proliferation assay, immunofluorescence, cytofluorimetry, time lapse microscopy, and colony formation in soft agar. Treatment of the cells with SNS-314 mesylate inhibited proliferation in a time- and dose-dependent manner, with IC(50) comprised between 2.6 nM and 26.6 nM. CAL-62 cells exposed for 24 h to SNS-314 mesylate 100 nM evidenced a significant augmentation of the apoptotic index. Time-lapse video-microscopy of CAL-62 cells showed that SNS-314 mesylate prevents the completion of mitosis leading to polyploidy. Western blot experiments demonstrated that the auto-phosphorylation of the Aurora kinases as well as histone H3 phosphorylation in CAL-62 treated cells was inhibited. Furthermore, the drug inhibited colony formation in soft agar of all cell lines. Reference: Clin Ter. 2012;163(5):e307-13. http://www.seu-roma.it/riviste/clinica_terapeutica/apps/autos.php?id=1050 |
| In vivo activity: | In the HCT116 human colon cancer xenograft model, administration of 50 and 100 mg/kg SNS-314 led to dose-dependent inhibition of histone H3 phosphorylation for at least 10 h, indicating effective Aurora-B inhibition in vivo. HCT116 tumors from mice treated with SNS-314 showed potent and sustained responses including reduction of phosphorylated histone H3 levels, increased caspase-3 and appearance of increased nuclear size. The compound showed significant tumor growth inhibition in a dose-dependent manner under a variety of dosing schedules including weekly, bi-weekly, and 5 days on/9 days off. Reference: Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17. https://link.springer.com/article/10.1007%2Fs00280-009-1076-8 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.9 | 234.14 |
The following data is based on the product molecular weight 430.93 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Baldini E, Sorrenti S, D'Armiento E, Guaitoli E, Morrone S, D'Andrea V, Gnessi L, Moretti C, Antonelli A, Catania A, De Antoni E, Ulisse S. Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines. Clin Ter. 2012;163(5):e307-13. PMID: 23099978. 2. Arbitrario JP, Belmont BJ, Evanchik MJ, Flanagan WM, Fucini RV, Hansen SK, Harris SO, Hashash A, Hoch U, Hogan JN, Howlett AR, Jacobs JW, Lam JW, Ritchie SC, Romanowski MJ, Silverman JA, Stockett DE, Teague JN, Zimmerman KM, Taverna P. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17. doi: 10.1007/s00280-009-1076-8. Epub 2009 Aug 1. PMID: 19649632. |
| In vitro protocol: | 1. Baldini E, Sorrenti S, D'Armiento E, Guaitoli E, Morrone S, D'Andrea V, Gnessi L, Moretti C, Antonelli A, Catania A, De Antoni E, Ulisse S. Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines. Clin Ter. 2012;163(5):e307-13. PMID: 23099978. |
| In vivo protocol: | 1. Arbitrario JP, Belmont BJ, Evanchik MJ, Flanagan WM, Fucini RV, Hansen SK, Harris SO, Hashash A, Hoch U, Hogan JN, Howlett AR, Jacobs JW, Lam JW, Ritchie SC, Romanowski MJ, Silverman JA, Stockett DE, Teague JN, Zimmerman KM, Taverna P. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17. doi: 10.1007/s00280-009-1076-8. Epub 2009 Aug 1. PMID: 19649632. |
1: Liu F, Wang G, Wang X, Che Z, Dong W, Guo X, Wang Z, Chen P, Hou D, Zhang Q, Zhang W, Pan Y, Yang D, Liu H. Targeting high Aurora kinases expression as an innovative therapy for hepatocellular carcinoma. Oncotarget. 2017 Apr 25;8(17):27953-27965. doi: 10.18632/oncotarget.15853. PubMed PMID: 28427193; PubMed Central PMCID: PMC5438621.
2: Quagliariello V, Armenia E, Aurilio C, Rosso F, Clemente O, de Sena G, Barbarisi M, Barbarisi A. New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase. J Cell Physiol. 2016 Aug;231(8):1784-95. doi: 10.1002/jcp.25283. Epub 2016 Feb 2. PubMed PMID: 26660542.
3: Sarvagalla S, Coumar MS. Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors. Curr Cancer Drug Targets. 2015;15(5):375-93. Review. PubMed PMID: 25895501.
4: Cheung CH, Sarvagalla S, Lee JY, Huang YC, Coumar MS. Aurora kinase inhibitor patents and agents in clinical testing: an update (2011 - 2013). Expert Opin Ther Pat. 2014 Sep;24(9):1021-38. doi: 10.1517/13543776.2014.931374. Epub 2014 Jun 26. Review. PubMed PMID: 24965505.
5: Baldini E, Sorrenti S, D'Armiento E, Guaitoli E, Morrone S, D'Andrea V, Gnessi L, Moretti C, Antonelli A, Catania A, De Antoni E, Ulisse S. Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines. Clin Ter. 2012;163(5):e307-13. PubMed PMID: 23099978.
6: Zhang B, Li Y, Zhang H, Ai C. 3D-QSAR and molecular docking studies on derivatives of MK-0457, GSK1070916 and SNS-314 as inhibitors against Aurora B kinase. Int J Mol Sci. 2010 Nov 2;11(11):4326-47. doi: 10.3390/ijms11114326. PubMed PMID: 21151441; PubMed Central PMCID: PMC3000085.
7: Lok W, Klein RQ, Saif MW. Aurora kinase inhibitors as anti-cancer therapy. Anticancer Drugs. 2010 Apr;21(4):339-50. doi: 10.1097/CAD.0b013e3283350dd1. Review. PubMed PMID: 20016367.
8: Arbitrario JP, Belmont BJ, Evanchik MJ, Flanagan WM, Fucini RV, Hansen SK, Harris SO, Hashash A, Hoch U, Hogan JN, Howlett AR, Jacobs JW, Lam JW, Ritchie SC, Romanowski MJ, Silverman JA, Stockett DE, Teague JN, Zimmerman KM, Taverna P. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17. doi: 10.1007/s00280-009-1076-8. Epub 2009 Aug 1. PubMed PMID: 19649632.
9: Zhong M, Bui M, Shen W, Baskaran S, Allen DA, Elling RA, Flanagan WM, Fung AD, Hanan EJ, Harris SO, Heumann SA, Hoch U, Ivy SN, Jacobs JW, Lam S, Lee H, McDowell RS, Oslob JD, Purkey HE, Romanowski MJ, Silverman JA, Tangonan BT, Taverna P, Yang W, Yoburn JC, Yu CH, Zimmerman KM, O'Brien T, Lew W. 2-Aminobenzimidazoles as potent Aurora kinase inhibitors. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5158-61. doi: 10.1016/j.bmcl.2009.07.016. Epub 2009 Jul 9. PubMed PMID: 19646866.
10: VanderPorten EC, Taverna P, Hogan JN, Ballinger MD, Flanagan WM, Fucini RV. The Aurora kinase inhibitor SNS-314 shows broad therapeutic potential with chemotherapeutics and synergy with microtubule-targeted agents in a colon carcinoma model. Mol Cancer Ther. 2009 Apr;8(4):930-9. doi: 10.1158/1535-7163.MCT-08-0754. PubMed PMID: 19372566.
11: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57. PubMed PMID: 19357798.
12: Oslob JD, Heumann SA, Yu CH, Allen DA, Baskaran S, Bui M, Delarosa E, Fung AD, Hashash A, Hau J, Ivy S, Jacobs JW, Lew W, Maung J, McDowell RS, Ritchie S, Romanowski MJ, Silverman JA, Yang W, Zhong M, Fuchs-Knotts T. Water-soluble prodrugs of an Aurora kinase inhibitor. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1409-12. doi: 10.1016/j.bmcl.2009.01.043. Epub 2009 Jan 19. PubMed PMID: 19186057.
13: Oslob JD, Romanowski MJ, Allen DA, Baskaran S, Bui M, Elling RA, Flanagan WM, Fung AD, Hanan EJ, Harris S, Heumann SA, Hoch U, Jacobs JW, Lam J, Lawrence CE, McDowell RS, Nannini MA, Shen W, Silverman JA, Sopko MM, Tangonan BT, Teague J, Yoburn JC, Yu CH, Zhong M, Zimmerman KM, O'Brien T, Lew W. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4. doi: 10.1016/j.bmcl.2008.07.073. Epub 2008 Jul 24. PubMed PMID: 18678489.
