| Size | Price | Stock | Qty |
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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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| 250mg |
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| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
uPA (Ki = 10 nM)
uPA (Ki = 10 nM) |
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| ln Vitro |
UK-3718046 (IC50=0.89 µM) has the ability to inhibit exogenous uPA in human chronic wound fluid in vitro[1].
UK-371804 is a reversible, substrate-competitive inhibitor of urokinase-type plasminogen activator (uPA) with a Ki of 10 nM. It demonstrates excellent enzyme potency and a remarkable selectivity profile, showing 4000-fold selectivity over tissue plasminogen activator (tPA) and 2700-fold selectivity over plasmin. The compound also exhibits excellent selectivity over Factor IXa and Xa. In human chronic wound fluid, UK-371804 inhibits exogenous uPA activity with an IC50 of 0.89 µM, confirming its efficacy in a complex biological environment. The compound effectively blocks EGR-FMK from binding human uPA even in the presence of tissue proteins, indicating that it can compete with other uPA-binding molecules in vivo. UK-371804 belongs to the 1-(7-sulfonamidoisoquinolinyl)guanidine class of uPA inhibitors and was selected for preclinical evaluation based on its exceptional potency and selectivity profile. |
| ln Vivo |
UK-3718046 can penetrate pig wounds in a porcine acute excisional wound model in vivo and inhibit exogenous uPA activity without negatively affecting wound healing parameters after topical administration[1].
UK-371804 demonstrates excellent enzyme potency with a Ki of 10 nM in enzyme assays. It inhibits exogenous uPA in human chronic wound fluid with an IC50 of 0.89 µM, confirming its activity in a complex biological matrix. The compound exhibits remarkable selectivity, showing 4000-fold selectivity over tissue plasminogen activator (tPA) and 2700-fold selectivity over plasmin. It also shows excellent selectivity over Factor IXa and Xa. UK-371804 effectively blocks EGR-FMK from binding human uPA even in the presence of tissue proteins, confirming its ability to engage its target in a physiologically relevant environment. |
| Enzyme Assay |
UK-371804 has an IC50 of 0.89 μM for inhibiting exogenous uPA in human chronic wound fluid. UK-371804 has a remarkable selectivity profile (4000-fold versus tPA and 2700-fold versus plasmin) and excellent enzyme potency (Ki=10nM).
Enzyme inhibition assays measure the compound's ability to inhibit uPA catalytic activity using chromogenic or fluorogenic substrates. The Ki value of 10 nM is determined from steady-state kinetic analyses. Selectivity profiling is conducted against related serine proteases including tissue plasminogen activator (tPA), plasmin, Factor IXa, and Factor Xa to establish the selectivity ratios of 4000-fold over tPA, 2700-fold over plasmin, and excellent selectivity over Factor IXa and Xa. |
| Cell Assay |
Cell-based assays evaluate the inhibition of exogenous uPA activity in human chronic wound fluid. Wound fluid samples are incubated with UK-371804 at various concentrations, and residual uPA activity is measured using specific substrates. The IC50 value of 0.89 µM is calculated from dose-response curves. Cytotoxicity and effects on cell viability are also assessed in relevant cell types to confirm that the compound's inhibitory activity is not due to non-specific cellular toxicity.
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| Animal Protocol |
A porcine acute excisional wound model
10 mg/mL topical delivery In a porcine acute excisional wound model, two female pigs receive eight excisional wounds. Wounds are dressed and treated daily for 10 days with either 1 mL of a 10 mg/mL formulation of UK-371804 in hydrogel vehicle or vehicle alone as control. Wound tissue penetration is assessed, and uPA activity inhibition is measured. Wound healing parameters are monitored for adverse effects. The results show that when applied topically, UK-371804 effectively penetrates into excisional wounds of experimental pigs with no adverse effect on wound closure. |
| ADME/Pharmacokinetics |
Pharmacokinetic data indicate that when applied topically, UK-371804 effectively penetrates into excisional wounds in pigs, suggesting good skin permeability. The compound is formulated in hydrogel vehicle for topical delivery. Dermal concentrations reach 41.8 µM, confirming effective tissue penetration at the site of action. Detailed systemic pharmacokinetic parameters such as half-life, clearance, and bioavailability have not been extensively reported in the available literature, as the compound was primarily developed for topical application where systemic exposure is expected to be minimal.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological assessment in the porcine wound model shows no adverse effects on wound healing parameters following topical administration. The compound has not been evaluated in standard toxicology studies for human use, and comprehensive systemic toxicity data are limited. Standard laboratory safety precautions should be observed during handling, including the use of appropriate personal protective equipment. The compound is not intended for human therapeutic use and should be handled as a research chemical.
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| References | |
| Additional Infomation |
UK-371804 belongs to the 1-(7-sulfonamidoisoquinolinyl)guanidine class of uPA inhibitors. It was selected for preclinical evaluation as a candidate for chronic dermal ulcer treatment based on its exceptional potency and selectivity profile. The compound has been validated in both in vitro human chronic wound fluid assays and in vivo porcine excisional wound models. No clinical trials have been reported for this compound, and it remains a research tool for studying uPA biology and wound healing. The compound's chemical name is 2-(((4-Chloro-1-guanidino-7-isoquinolinyl)sulfonyl)amino)-isobutyric acid hydrochloride.
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| Molecular Formula |
C14H16CLN5O4S.HCL
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| Molecular Weight |
422.29
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| Exact Mass |
421.037
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| CAS # |
256476-36-5
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| Related CAS # |
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| PubChem CID |
16657953
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
644
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C(=O)O)NS(=O)(=O)C1=CC2=C(C=C1)C(=CN=C2N=C(N)N)Cl.Cl
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| InChi Key |
IUBFETAFRGVODB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H16ClN5O4S.ClH/c1-14(2,12(21)22)20-25(23,24)7-3-4-8-9(5-7)11(19-13(16)17)18-6-10(8)15;/h3-6,20H,1-2H3,(H,21,22)(H4,16,17,18,19);1H
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| Chemical Name |
2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-2-methylpropanoic acid;hydrochloride
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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 | 2.3680 mL | 11.8402 mL | 23.6804 mL | |
| 5 mM | 0.4736 mL | 2.3680 mL | 4.7361 mL | |
| 10 mM | 0.2368 mL | 1.1840 mL | 2.3680 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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