| Size | Price | Stock | Qty |
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| Targets |
UK-356618 targets matrix metalloproteinase 3 (MMP-3) with high selectivity. It has an IC50 of 5.9 nM for MMP-3. Selectivity is 140-fold vs MMP-1, -2, -9, and -14. Its inhibitory activities against MMP-1 (IC50 = 51 μM), MMP-2 (1.79 μM), MMP-9 (0.84 μM), MMP-13 (0.073 μM), and MMP-14 (1.9 μM) are all weaker than against MMP-3. This selectivity profile makes it a valuable tool for studying MMP-3-specific functions.
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| ln Vitro |
Compared to other MMPs, UK 356618 exhibits broader features [1]. MMP-13 has a strong correlation with elevated TNF-α or IL-6 in tumor metastasis. Lack of MMP-13 eliminates TNF-α's impact on cell migration. The effect of TNF-α on NCI-H446 cell movement was significantly abolished by UK 356618 treatment [2].
UK-356618 demonstrates potent and selective MMP-3 inhibition with an IC50 of 5.9 nM. It has the potential to inhibit interleukin (IL)-6-induced cell migration in NCI H446 small cell lung cancer cells in vitro. The compound’s selectivity for MMP-3 over other MMPs (140-fold vs MMP-1, -2, -9, and -14) makes it useful for dissecting MMP-3-specific roles in various biological processes. |
| ln Vivo |
The administration of UK 356618 (15 mg/kg; intravenous injection; 24 or 7 days; capsule Wistar status) dramatically lowers the brain's MMP3 activity [3].
In vivo activity data for UK-356618 are not extensively detailed in the available literature. As an MMP-3 inhibitor, the compound would be expected to modulate extracellular matrix remodeling, inflammatory responses, and cell migration in vivo. Its potential to inhibit IL-6-induced cell migration in vitro suggests possible anti-inflammatory or anti-metastatic activity in vivo. Specific in vivo efficacy data are not reported. |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for UK-356618 involve MMP activity assays using purified enzymes. IC50 values are determined for MMP-3 (5.9 nM) and selectivity is confirmed against MMP-1, MMP-2, MMP-9, MMP-13, and MMP-14. Enzyme activity is measured using fluorogenic substrates, and inhibition is calculated relative to controls.
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| Cell Assay |
In vitro cell-based assays for UK-356618 use rat C6 astroglial cells to study its effect on amitriptyline-induced GDNF mRNA expression and MMP-9 activation. NCI H446 small cell lung cancer cells are used to assess inhibition of IL-6-induced cell migration. Cells are treated with UK-356618 at various concentrations, and migration is assessed using wound healing or transwell assays.
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| Animal Protocol |
Animal/Disease Models: hyperglycemic male Wistar rats middle cerebral artery occlusion injection (MCAO) [3]
Doses: 15 mg/kg Route of Administration: intravenous (iv) (iv)injection; 24 hrs (hrs (hours)) or 7 days Experimental Results: MMP3 activity in the brain was Dramatically diminished. In vivo animal studies for UK-356618 are not detailed in the available literature. As an MMP-3 inhibitor, typical in vivo evaluation would involve animal models of inflammation, arthritis, or cancer metastasis. The compound’s ability to inhibit MMP-3-mediated tissue remodeling and cell migration would be assessed in these models. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of UK-356618 are not extensively reported. The compound has a molecular formula of C34H43N3O4. It is soluble in DMSO at ≥25 mg/mL and appears as a white to tan powder. Purity is ≥98% (HPLC). Optical activity: [α]/D >+25.0°, c = 0.5 in methanol. Storage: at 2–8°C. The compound has the SMILES string C[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCc1ccc(c(C)c1)-c2ccccc2)CC(=O)NO)C(C)(C)C)c3ccccc3.
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| Toxicity/Toxicokinetics |
Specific toxicological data for UK-356618 are limited. The compound is classified as Acute Tox. 4 Oral and is a combustible solid (Storage Class 11) with WGK 3. It is intended for laboratory research use only. As an MMP-3 inhibitor, potential toxicities would relate to effects on extracellular matrix remodeling, though formal toxicological profiles are not extensively detailed.
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| References |
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| Additional Infomation |
(2R)-N-[(2S)-3,3-dimethyl-1-oxo-1-[[(1R)-1-phenylethyl]amino]but-2-yl]-N'-hydroxy-2-[3-(3-methyl-4-phenylphenyl)propyl]butanediamide is a secondary carboxylamide.
UK-356618 (CAS 230961-08-7) is a potent and selective matrix metalloproteinase 3 (MMP-3) inhibitor with an IC50 of 5.9 nM. It shows markedly lower potency against MMP-1 (51 μM), MMP-2 (1.79 μM), MMP-9 (0.84 μM), MMP-13 (0.073 μM), and MMP-14 (1.9 μM). The compound inhibits IL-6-induced cell migration in small cell lung cancer cells. No clinical trial or approved indication data are available. |
| Molecular Formula |
C34H43N3O4
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| Molecular Weight |
557.722929239273
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| Exact Mass |
557.325
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| CAS # |
230961-08-7
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| PubChem CID |
10370504
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| Appearance |
White to light yellow solid powder
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| LogP |
8.425
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
41
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| Complexity |
828
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=C(C=CC(=C1)CCC[C@H](CC(=O)NO)C(=O)N[C@H](C(=O)N[C@H](C)C2=CC=CC=C2)C(C)(C)C)C3=CC=CC=C3
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| InChi Key |
JJHRUUKMPWUYIB-HVOSOHGQSA-N
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| InChi Code |
InChI=1S/C34H43N3O4/c1-23-21-25(19-20-29(23)27-16-10-7-11-17-27)13-12-18-28(22-30(38)37-41)32(39)36-31(34(3,4)5)33(40)35-24(2)26-14-8-6-9-15-26/h6-11,14-17,19-21,24,28,31,41H,12-13,18,22H2,1-5H3,(H,35,40)(H,36,39)(H,37,38)/t24-,28-,31-/m1/s1
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| Chemical Name |
(2R)-N-[(2S)-3,3-dimethyl-1-oxo-1-[[(1R)-1-phenylethyl]amino]butan-2-yl]-N'-hydroxy-2-[3-(3-methyl-4-phenylphenyl)propyl]butanediamide
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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 : ~25 mg/mL (~44.83 mM)
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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 | 1.7930 mL | 8.9651 mL | 17.9301 mL | |
| 5 mM | 0.3586 mL | 1.7930 mL | 3.5860 mL | |
| 10 mM | 0.1793 mL | 0.8965 mL | 1.7930 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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