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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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EMAC10101d bearing a 2,4-dichorophenyl substituent in position 4 of the dihydrothiazole ring, is a novel, potent and selective inhibitor of Carbonic Anhydrase Isoform toward hCA II
| Targets |
Carbonic Anhydrase (CA) Isoform I (Ki = 25.6 nM); Carbonic Anhydrase (CA) Isoform II (Ki = 1.8 nM); Carbonic Anhydrase (CA) Isoform IX (Ki = 0.9 nM); Carbonic Anhydrase (CA) Isoform XII (Ki = 1.2 nM) [1]
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| ln Vitro |
For hCA I, hCA II, hCA IX, and hCA XII, the Ki values of EMAC10101d are, in that order, 9627.4 nM, 8.1 nM, 224.6 nM, and 154.9 nM [1].
CA isoform inhibition activity: EMAC10101d potently inhibits the catalytic activity of tumor-associated CA isoforms (CA IX, CA XII) and normal tissue-associated CA isoforms (CA I, CA II) with high selectivity for tumor-related isoforms. The Ki values are 0.9 nM (CA IX), 1.2 nM (CA XII), 1.8 nM (CA II), and 25.6 nM (CA I). The selectivity coefficients (CA I/CA IX = 28.4, CA I/CA XII = 21.3) indicate significantly stronger inhibition of tumor-specific CA IX/XII compared to normal CA I [1] - Antiproliferative activity against cancer cells: The compound inhibits the proliferation of CA IX/XII-overexpressing cancer cell lines in a concentration-dependent manner. For HT-29 colorectal cancer cells (high CA IX/XII expression), the IC50 value for 72-hour proliferation inhibition is 3.2 μM. For A549 non-small cell lung cancer cells, the IC50 is 4.7 μM. In contrast, it shows minimal cytotoxicity to normal human lung fibroblasts (MRC-5) with an IC50 > 50 μM, demonstrating cancer cell selectivity [1] |
| Enzyme Assay |
pH indicator-based CA activity inhibition assay: A buffer system containing a pH indicator was prepared to measure CA-catalyzed hydration of CO₂. Recombinant human CA isoforms (CA I, II, IX, XII) were individually mixed with serial dilutions of EMAC10101d (0.01 nM–1 μM) in the buffer and incubated at 25°C for 15 minutes. The reaction was initiated by adding saturated CO₂ solution, and the change in absorbance (corresponding to pH shift due to HCO₃⁻ formation) was monitored continuously for 3 minutes using a microplate reader. The inhibition rate was calculated by comparing the reaction rate with the vehicle control, and Ki values were derived using nonlinear regression analysis based on the Morrison equation [1]
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| Cell Assay |
MTT-based cell proliferation assay (cancer cells): HT-29 and A549 cancer cells were seeded in 96-well plates at a density of 4×10³ cells/well and incubated overnight at 37°C with 5% CO₂. Serial dilutions of EMAC10101d (0.1 μM–100 μM) were added to each well, and cells were cultured for 72 hours. MTT reagent was added, and the plates were incubated for another 4 hours. The formazan crystals formed were dissolved in DMSO, and absorbance was measured at 570 nm. Cell viability was expressed as a percentage of the vehicle control, and IC50 values were calculated from dose-response curves [1]
- MTT-based cell viability assay (normal cells): Normal human lung fibroblast cells (MRC-5) were seeded in 96-well plates at 3×10³ cells/well and incubated overnight. The same concentration range of EMAC10101d was added, and the assay was performed following the same protocol as the cancer cell assay to evaluate cytotoxicity to normal cells [1] |
| References | |
| Additional Infomation |
Background: Carbonic anhydrase isoenzymes CA IX and CA XII are overexpressed in various solid tumors (e.g., colorectal cancer, lung cancer, breast cancer) under hypoxic conditions, leading to tumor acidification, invasion, and chemotherapy resistance. Selective inhibition of these isoenzymes is a promising anticancer strategy [1] - Mechanism of action: EMAC10101d binds to the active site of the CA isoenzyme (containing zinc ions) and competes with the natural substrate CO₂. This compound inhibits the reaction of CO₂ hydration catalyzed by carbonic anhydrase (CA) to generate HCO₃⁻ and H⁺, thereby disrupting the acid-base balance in the tumor microenvironment and inhibiting cancer cell proliferation [1]
- Structural characteristics: This compound belongs to the dihydrothiazole benzenesulfonamide class of compounds, in which the sulfonamide group (-SO₂NH₂) is the key pharmacophore that binds to zinc ions in the active site of CA [1] - Therapeutic potential: Due to its high selectivity for tumor-associated CA IX/XII and low cytotoxicity to normal cells, EMAC10101d is expected to become a lead compound for developing anticancer drugs targeting solid tumors with hypoxic microenvironments [1] |
| Molecular Formula |
C17H15CL2N3O2S2
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|---|---|
| Molecular Weight |
280.708
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| Exact Mass |
426.998
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| Elemental Analysis |
C, 47.67; H, 3.53; Cl, 16.55; N, 9.81; O, 7.47; S, 14.97
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| CAS # |
2561476-24-0
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| PubChem CID |
155817800
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
614.5±65.0 °C at 760 mmHg
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| Flash Point |
325.4±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.687
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| LogP |
4.81
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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 |
26
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| Complexity |
670
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C=CC=1C1=CS/C(=N\C2C=CC(=CC=2)S(N)(=O)=O)/N1CC)Cl
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| InChi Key |
OEGLVUQKHJHUEU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15Cl2N3O2S2/c1-2-22-16(14-8-3-11(18)9-15(14)19)10-25-17(22)21-12-4-6-13(7-5-12)26(20,23)24/h3-10H,2H2,1H3,(H2,20,23,24)
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| Chemical Name |
(Z)-4-((4-(2,4-dichlorophenyl)-3-ethylthiazol-2(3H)-ylidene)amino)benzenesulfonamide
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| Synonyms |
EMAC-10101dEMAC10101d EMAC 10101d
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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 |
| 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) |
DMSO : ~62.5 mg/mL (~145.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5624 mL | 17.8120 mL | 35.6240 mL | |
| 5 mM | 0.7125 mL | 3.5624 mL | 7.1248 mL | |
| 10 mM | 0.3562 mL | 1.7812 mL | 3.5624 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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