Related CAS #
422513-13-1 (free base); unknown (HCl)
Synonym
Hesperadin; Hesperadine.
IUPAC/Chemical Name
(Z)-N-(2-oxo-3-(phenyl((4-(piperidin-1-ylmethyl)phenyl)amino)methylene)indolin-5-yl)ethanesulfonamide
InChi Key
GLDSKRNGVVYJAB-DQSJHHFOSA-N
InChi Code
InChI=1S/C29H32N4O3S/c1-2-37(35,36)32-24-15-16-26-25(19-24)27(29(34)31-26)28(22-9-5-3-6-10-22)30-23-13-11-21(12-14-23)20-33-17-7-4-8-18-33/h3,5-6,9-16,19,30,32H,2,4,7-8,17-18,20H2,1H3,(H,31,34)/b28-27-
SMILES Code
CCS(=O)(NC1=CC2=C(NC(/C2=C(C3=CC=CC=C3)\NC4=CC=C(CN5CCCCC5)C=C4)=O)C=C1)=O
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
Biological target:
Hesperadin is an ATP competitive indolinone inhibitor of Aurora A and B. Hesperadin inhibits Aurora B with an IC50 of 250 nM.
In vitro activity:
After 24 hr exposure of BF cultures to 100 nM Hesperadin, cells contained a multi-lobed nucleus, numerous kDNA and numerous flagella (Fig. 6C, panels c-d); a pattern that phenocopied the loss of TbAUK1 with RNAi. The changes in cell population were quantified (Fig. 6B, right panel). In a wild-type BF population, approximately 60% of cells are in the 1N1K configuration, defined by a single nucleus (N) and a single kinetoplast (K). Within 24 hr of TbAUK1 depletion with RNAi, 1N1K cells declined to 8% of the population, while cells with the unusual configuration of more than 3K and an indeterminate number of nuclei (XN; K>3) increased to 81% of the population. After 24 hr exposure to 200 nM Hesperadin, cells with a 1N1K configuration dropped to 28% of the population, while cells with XN; K>3 increased to 25% of the population. Within 48 hr, cells with a XN; K>3 configuration increased to 48% of the population (Fig. 6C, right panel).
Reference: Mol Microbiol. 2009 Apr;72(2):442-58. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19320832/
In vivo activity:
It was confirmed that hesperadin administration for ICH mice significantly improved edema and alleviated neurological deficits at 12 h after ICH compared to the ICH group. MST4 expression in ICH mice treated with hesperadin was significantly lower than ICH mice, which proved the potential of hesperadin as an MST4 inhibitor. It was found that hesperadin is neuroprotective, which could ameliorate brain edema and behavioral deficits after experimental ICH in mice. In this study, hesperadin was confirmed to show a neuroprotective effect and can improve brain edema and neurofunction deficits in ICH mice.
Reference: Behav Neurol. 2020 Feb 3;2020:2476861. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32089749/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
193.55 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
516.65
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 |
In vitro protocol:
1. Jetton N, Rothberg KG, Hubbard JG, Wise J, Li Y, Ball HL, Ruben L. The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms. Mol Microbiol. 2009 Apr;72(2):442-58. doi: 10.1111/j.1365-2958.2009.06657.x. Epub 2009 Mar 6. PMID: 19320832; PMCID: PMC2697958.
In vivo protocol:
1. Wu X, Wu J, Hu W, Wang Q, Liu H, Chu Z, Lv K, Xu Y. MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in Intracerebral Hemorrhage Mice. Behav Neurol. 2020 Feb 3;2020:2476861. doi: 10.1155/2020/2476861. PMID: 32089749; PMCID: PMC7023841.
1: Jetton N, Rothberg KG, Hubbard JG, Wise J, Li Y, Ball HL, Ruben L. The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms. Mol Microbiol. 2009 Apr;72(2):442-58. doi: 10.1111/j.1365-2958.2009.06657.x. Epub 2009 Mar 6. PubMed PMID: 19320832; PubMed Central PMCID: PMC2697958.
2: Ladygina NG, Latsis RV, Yen T. [Effect of the pharmacological agent hesperadin on breast and prostate tumor cultured cells]. Biomed Khim. 2005 Mar-Apr;51(2):170-6. Russian. PubMed PMID: 15945350.
3: Sessa F, Mapelli M, Ciferri C, Tarricone C, Areces LB, Schneider TR, Stukenberg PT, Musacchio A. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell. 2005 Apr 29;18(3):379-91. PubMed PMID: 15866179.
4: Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM. The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol. 2003 Apr 28;161(2):281-94. Epub 2003 Apr 21. PubMed PMID: 12707311; PubMed Central PMCID: PMC2172906.
