Synonym
ELR510444; ELR-510444; ELR 510444.
IUPAC/Chemical Name
N-(5-(5-cyanothiophen-2-yl)-2-methylphenyl)-4-methylbenzenesulfonamide
InChi Key
GRYXROIHHXHFND-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H16N2O2S2/c1-13-3-8-17(9-4-13)25(22,23)21-18-11-15(6-5-14(18)2)19-10-7-16(12-20)24-19/h3-11,21H,1-2H3
SMILES Code
O=S(C1=CC=C(C)C=C1)(NC2=CC(C3=CC=C(C#N)S3)=CC=C2C)=O
Appearance
Yellow 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:
ELR-510444 is a novel microtubule disruptor with potential antivascular effects and in vivo antitumor efficacy, causing a loss of cellular microtubules and the formation of aberrant mitotic spindles and leading to mitotic arrest and apoptosis of cancer cells.
In vitro activity:
ELR510444 has potent microtubule-disrupting activity, causing a loss of cellular microtubules and the formation of aberrant mitotic spindles and leading to mitotic arrest and apoptosis of cancer cells. ELR510444 potently inhibited cell proliferation with an IC(50) value of 30.9 nM in MDA-MB-231 cells, inhibited the rate and extent of purified tubulin assembly, and displaced colchicine from tubulin, indicating that the drug directly interacts with tubulin at the colchicine-binding site. ELR510444 is not a substrate for the P-glycoprotein drug transporter and retains activity in βIII-tubulin-overexpressing cell lines, suggesting that it circumvents both clinically relevant mechanisms of drug resistance to this class of agents. These data show a close correlation between the concentration of ELR510444 required for inhibition of cellular proliferation and that required to cause significant loss of cellular microtubule density, consistent with its activity as a microtubule depolymerizer.
Reference: J Pharmacol Exp Ther. 2011 Mar;336(3):652-60. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21148249/
In vivo activity:
To further investigate the anticancer activity of ELR510444, its efficacy was evaluated in the 786-O and A498 RCC mouse xenograft models. 786-O and A498 tumor-bearing animals were randomized into groups and given 8 mg/kg ELR510444 orally for 2 weeks on a QDx5 (every day for 5 days) schedule. Treatment with ELR510444 significantly decreased mean tumor volume in both xenograft models compared to the vehicle-treated controls (Figure 6A). Importantly, ELR510444 was very well tolerated as no significant animal weight loss was observed throughout the duration of the study (Figure 6B). Further analysis of tumors harvested at the end of the study revealed a significant reduction in tumor cell proliferation as measured by PCNA staining (Figure 6C) and an increase in cleaved caspase-3 levels, a marker of apoptosis (Figure 6D). Collectively, these data demonstrate that ELR510444 has significant in vivo activity in RCC tumor models.
Reference: PLoS One. 2012;7(1):e31120. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22295124/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
73.0 |
198.12 |
| Ethanol |
24.0 |
65.13 |
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
368.47
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. Carew JS, Esquivel JA 2nd, Espitia CM, Schultes CM, Mülbaier M, Lewis JD, Janssen B, Giles FJ, Nawrocki ST. ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma. PLoS One. 2012;7(1):e31120. doi: 10.1371/journal.pone.0031120. Epub 2012 Jan 25. PMID: 22295124; PMCID: PMC3266297.
2. Risinger AL, Westbrook CD, Encinas A, Mülbaier M, Schultes CM, Wawro S, Lewis JD, Janssen B, Giles FJ, Mooberry SL. ELR510444, a novel microtubule disruptor with multiple mechanisms of action. J Pharmacol Exp Ther. 2011 Mar;336(3):652-60. doi: 10.1124/jpet.110.175331. Epub 2010 Dec 9. PMID: 21148249; PMCID: PMC3061540.
In vivo protocol:
1. Carew JS, Esquivel JA 2nd, Espitia CM, Schultes CM, Mülbaier M, Lewis JD, Janssen B, Giles FJ, Nawrocki ST. ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma. PLoS One. 2012;7(1):e31120. doi: 10.1371/journal.pone.0031120. Epub 2012 Jan 25. PMID: 22295124; PMCID: PMC3266297.
2. Risinger AL, Westbrook CD, Encinas A, Mülbaier M, Schultes CM, Wawro S, Lewis JD, Janssen B, Giles FJ, Mooberry SL. ELR510444, a novel microtubule disruptor with multiple mechanisms of action. J Pharmacol Exp Ther. 2011 Mar;336(3):652-60. doi: 10.1124/jpet.110.175331. Epub 2010 Dec 9. PMID: 21148249; PMCID: PMC3061540.
1: Carew JS, Esquivel JA 2nd, Espitia CM, Schultes CM, Mülbaier M, Lewis JD, Janssen B, Giles FJ, Nawrocki ST. ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma. PLoS One. 2012;7(1):e31120. doi: 10.1371/journal.pone.0031120. Epub 2012 Jan 25. PubMed PMID: 22295124; PubMed Central PMCID: PMC3266297.
2: Risinger AL, Westbrook CD, Encinas A, Mülbaier M, Schultes CM, Wawro S, Lewis JD, Janssen B, Giles FJ, Mooberry SL. ELR510444, a novel microtubule disruptor with multiple mechanisms of action. J Pharmacol Exp Ther. 2011 Mar;336(3):652-60. doi: 10.1124/jpet.110.175331. Epub 2010 Dec 9. PubMed PMID: 21148249; PubMed Central PMCID: PMC3061540.
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