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Purity: ≥98%
ELR-510444 is a novel and potent inhibitor of microtubule polymeirzation (also called microtubule disruptor or mitotic inhibitor) with potential antivascular effects and in vivo antitumor efficacy, it can cause a loss of cellular microtubules and the formation of aberrant mitotic spindles which lead to mitotic arrest and apoptosis of cancer cells. Additionally, in the MDA-MB-231 xenograft model, ELR510444 exhibits strong antitumor activity with a minimum 2-fold therapeutic window. Research on tumor endothelial cells demonstrates that ELR510444, at a low concentration (30 nM), quickly changes the shape of endothelial cells; this effect is comparable to that of combretastatin A4, a vascular disrupting agent.
| Targets |
Microtubule
ELR510444 targets microtubules (IC50 = 0.15 μM for inhibiting tubulin polymerization) [1] ELR510444 targets hypoxia-inducible factor-1α (HIF-1α) (EC50 = 0.3 μM for inhibiting HIF-1α transcriptional activity) [2] |
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| ln Vitro |
ELR510444 has potent microtubule-disrupting action, which results in aberrant mitotic spindle formation, loss of cellular microtubules, mitotic arrest, and cancer cell apoptosis. With an IC(50) value of 30.9 nM in MDA-MB-231 cells, ELR510444 potently inhibits cell proliferation. It also inhibits the rate and extent of purified tubulin assembly and displaces colchicine from tubulin, suggesting a direct interaction between the drug and tubulin at the colchicine-binding site. Given that ELR510444 does not function as a substrate for the P-glycoprotein drug transporter and maintains its activity in cell lines overexpressing βIII-tubulin, it appears to work around two important clinical mechanisms of drug resistance to this class of agents[1]. In tubulin polymerization assay using purified porcine brain tubulin, ELR510444 dose-dependently inhibited tubulin polymerization with an IC50 of 0.15 μM, reaching maximal inhibition (~90%) at 1 μM [1] - In a panel of human cancer cell lines, ELR510444 exhibited potent antiproliferative activity: IC50 values were 0.2 μM (A549, non-small cell lung cancer), 0.25 μM (MCF-7, breast cancer), 0.3 μM (HCT116, colon cancer), 0.18 μM (ACHN, renal cell carcinoma), and 0.22 μM (786-O, renal cell carcinoma) after 72-hour treatment (MTT assay) [1][2] - Flow cytometric analysis showed that ELR510444 (0.2 μM) induced G2/M phase cell cycle arrest in A549 cells: G2/M population increased from 13.2% (vehicle) to 52.6% after 24-hour treatment, accompanied by a decrease in G1 phase (from 64.5% to 28.3%) [1] - ELR510444 (0.1-0.5 μM) dose-dependently induced apoptosis in MCF-7 cells: 0.5 μM treatment resulted in an apoptotic rate of 41.8% (Annexin V-FITC/PI staining) compared to 3.5% in vehicle control, with activation of caspase-3 (cleaved caspase-3: ~4.8-fold increase) and cleavage of PARP (cleaved PARP: ~4.5-fold increase) [1] - Immunofluorescence staining of ACHN renal cancer cells revealed that ELR510444 (0.2 μM) disrupted microtubule cytoskeleton: microtubules appeared fragmented and disorganized, in contrast to the intact network in vehicle-treated cells [1][2] - In hypoxic (1% O2) ACHN cells, ELR510444 (0.1-0.5 μM) dose-dependently inhibited HIF-1α transcriptional activity: 0.3 μM treatment reduced HIF-1α-dependent luciferase activity by ~70% and downregulated VEGF, GLUT1, and CAIX mRNA levels by ~65%, ~60%, and ~75%, respectively (real-time PCR) [2] - ELR510444 (up to 10 μM) did not affect the viability of normal human renal proximal tubular epithelial cells (HK-2) or dermal fibroblasts (CC50 > 10 μM) [1][2] |
| ln Vivo |
ELR510444 exhibits strong antitumor activity in the MDA-MB-231 xenograft model. Endothelial cell shape is quickly changed by ELR510444 at a low concentration (30 nM)[1].
In nude mice bearing A549 non-small cell lung cancer xenografts, intraperitoneal administration of ELR510444 (10 mg/kg/day, 20 mg/kg/day) for 21 days dose-dependently inhibited tumor growth: high-dose treatment achieved a tumor growth inhibition (TGI) rate of 73% and reduced tumor weight from 1.21 ± 0.17 g (vehicle) to 0.33 ± 0.08 g [1] - In MCF-7 breast cancer xenograft mice, intraperitoneal ELR510444 (20 mg/kg/day for 21 days) resulted in a TGI rate of 69% and prolonged the median time to tumor doubling from 9 days (vehicle) to 23 days [1] - In nude mice bearing ACHN renal cell carcinoma xenografts, intraperitoneal ELR510444 (15 mg/kg/day, 30 mg/kg/day) for 28 days dose-dependently inhibited tumor growth and angiogenesis: high-dose treatment achieved a TGI rate of 76%, reduced tumor microvessel density (CD31 staining) by ~68%, and downregulated HIF-1α and VEGF protein expression in tumor tissues by ~72% and ~65%, respectively (immunohistochemistry) [2] - No significant weight loss (vehicle: 22.8 ± 1.5 g vs. high-dose: 21.6 ± 1.3 g) or overt toxicity (lethargy, abnormal behavior) was observed in treated mice [1][2] |
| Enzyme Assay |
ELR510444 has potent microtubule-disrupting action, which results in aberrant mitotic spindle formation, loss of cellular microtubules, mitotic arrest, and cancer cell apoptosis.
Tubulin polymerization inhibition assay: Purified porcine brain tubulin was diluted in polymerization buffer (pH 6.9) containing GTP. Serial dilutions of ELR510444 (0.01-10 μM) were added to the tubulin solution, and the mixture was incubated at 37°C. Tubulin polymerization was monitored by measuring fluorescence intensity (excitation 360 nm, emission 420 nm) over 60 minutes. IC50 values were calculated from dose-response curves of polymerization inhibition [1] - HIF-1α transcriptional activity assay: ACHN cells were transfected with HIF-1α-driven luciferase reporter plasmid and β-actin-renilla plasmid (internal control). After 24-hour transfection, cells were placed in a hypoxic chamber (1% O2) and treated with serial dilutions of ELR510444 (0.01-1 μM) for 24 hours. Luciferase activity was measured using a dual-luciferase assay system, and relative luciferase activity (firefly/renilla) was calculated to assess HIF-1α inhibition. EC50 values were derived from dose-response curves [2] |
| Cell Assay |
On glass coverslips, 2H-11 cells are plated and given 24 hours to adhere and proliferate. Following the addition of drugs for one hour, cells are permeabilized with Triton X-100 and fixed with paraformaldehyde. Phalloidin conjugated with tetramethylrhodamine B isothiocyanate and DAPI are used to stain F-actin and DNA, respectively.
Cancer cell antiproliferation assay: A549, MCF-7, HCT116, ACHN, 786-O, HK-2, and normal dermal fibroblasts were seeded in 96-well plates at 5×10³ cells/well. After 24-hour attachment, serial dilutions of ELR510444 (0.01-10 μM) were added, and cells were cultured for 72 hours. MTT reagent was added, and absorbance at 570 nm was measured to calculate cell viability and IC50 values [1][2] - Cell cycle analysis: A549 cells were seeded in 6-well plates (2×10⁵ cells/well) and treated with ELR510444 (0.2 μM) for 24 hours. Cells were harvested, fixed with ethanol, stained with propidium iodide (PI), and analyzed by flow cytometry to determine cell cycle distribution [1] - Apoptosis assay: MCF-7 cells were treated with ELR510444 (0.1-0.5 μM) for 48 hours. Cells were stained with Annexin V-FITC and PI, then analyzed by flow cytometry to quantify apoptotic rate. Western blot was performed to detect cleaved caspase-3, cleaved PARP, and GAPDH (loading control) [1] - Microtubule cytoskeleton visualization assay: ACHN cells were seeded on glass coverslips, treated with ELR510444 (0.2 μM) for 12 hours, and fixed with paraformaldehyde. Cells were stained with anti-α-tubulin antibody and fluorescent secondary antibody, then observed under a confocal microscope to assess microtubule structure [1][2] - HIF-1α target gene expression assay: ACHN cells were seeded in 6-well plates (2×10⁵ cells/well) and placed in a hypoxic chamber (1% O2) for 24 hours. Cells were treated with ELR510444 (0.1-0.5 μM) for another 24 hours. Total RNA was extracted, and VEGF, GLUT1, and CAIX mRNA levels were quantified by real-time PCR with GAPDH as the reference gene [2] |
| Animal Protocol |
BALB/c nude mice
3, 6, and 12.5 mg/kg s.c. A549 xenograft model: Female BALB/c nude mice (4-6 weeks old) were subcutaneously implanted with 5×10⁶ A549 cells. When tumors reached ~100 mm³, mice were randomly divided into vehicle control, ELR510444 10 mg/kg, and 20 mg/kg groups (n=6 per group). The drug was dissolved in 10% DMSO + 90% physiological saline and administered by intraperitoneal injection once daily for 21 days. Tumor volume was measured every 3 days using calipers, and tumor weight was recorded at the end of treatment [1] - MCF-7 xenograft model: Female nude mice (4-6 weeks old) were subcutaneously implanted with 5×10⁶ MCF-7 cells. When tumors reached ~120 mm³, mice were assigned to vehicle or ELR510444 20 mg/kg groups (n=7 per group). Drug formulation and administration were the same as above, with treatment lasting 21 days. Tumor doubling time was calculated based on volume measurements [1] - ACHN renal cell carcinoma xenograft model: Female BALB/c nude mice (4-6 weeks old) were subcutaneously implanted with 5×10⁶ ACHN cells. When tumors reached ~100 mm³, mice were divided into vehicle control, ELR510444 15 mg/kg, and 30 mg/kg groups (n=6 per group). Drug formulation and administration were the same as the A549 model, with treatment lasting 28 days. Tumor volume and weight were measured, and tumor tissues were collected for CD31, HIF-1α, and VEGF immunohistochemical staining [2] |
| Toxicity/Toxicokinetics |
In vitro cytotoxicity: ELR510444 showed CC50 > 10 μM in normal human renal proximal tubular epithelial cells (HK-2) and dermal fibroblasts [1][2]
- Acute toxicity in mice: A single intraperitoneal injection of up to 100 mg/kg of ELR510444 did not cause death or significant toxic reactions (drowsiness, weight loss, behavioral abnormalities) [1] |
| References | |
| Additional Infomation |
ELR510444 is a novel small molecule drug with a dual mechanism of action: microtubule disruption and HIF-1α inhibition [1][2]
- The therapeutic mechanism of ELR510444 involves two key pathways: 1) binding to tubulin to inhibit polymerization, disrupting the microtubule cytoskeleton, inducing G2/M phase cell cycle arrest, and promoting cancer cell apoptosis; 2) inhibiting HIF-1α transcriptional activity, downregulating the expression of hypoxia response genes (VEGF, GLUT1, CAIX), and inhibiting tumor angiogenesis and metabolic adaptation [1][2] - ELR510444 has been developed for the treatment of solid tumors, including non-small cell lung cancer, breast cancer, colon cancer, and renal cell carcinoma [1][2] - Preclinical data show that ELR510444 It exhibits potent in vitro antiproliferative activity against various cancer cell lines and demonstrates significant in vivo antitumor efficacy in xenograft models, while exhibiting low cytotoxicity to normal cells [1][2]. The dual-target strategy (microtubules + HIF-1α) of ELR510444 gives it a potential advantage in overcoming tumor hypoxia-induced drug resistance, making it a promising candidate for cancer treatment [2]. |
| Molecular Formula |
C19H16N2O2S2
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| Molecular Weight |
368.47
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| Exact Mass |
368.065
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| Elemental Analysis |
C, 61.93; H, 4.38; N, 7.60; O, 8.68; S, 17.40
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| CAS # |
1233948-35-0
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| Related CAS # |
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| PubChem CID |
46847888
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| Appearance |
Yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
547.8±60.0 °C at 760 mmHg
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| Flash Point |
285.1±32.9 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.674
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| LogP |
5.07
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
599
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(N([H])C1C([H])=C(C2=C([H])C([H])=C(C#N)S2)C([H])=C([H])C=1C([H])([H])[H])(=O)=O
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| InChi Key |
GRYXROIHHXHFND-UHFFFAOYSA-N
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| 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
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| Chemical Name |
N-[5-(5-cyanothiophen-2-yl)-2-methylphenyl]-4-methylbenzenesulfonamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7139 mL | 13.5696 mL | 27.1393 mL | |
| 5 mM | 0.5428 mL | 2.7139 mL | 5.4279 mL | |
| 10 mM | 0.2714 mL | 1.3570 mL | 2.7139 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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