| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Human glutaminyl cyclase (hQC) [1] (Ki = 0.06 ± 0.0002 μM)
Secretory QC (sQC) [3] (Ki = 0.095 ± 0.003 μM) Golgi-resident QC (gQC) [3] (Ki = 1.817 ± 0.154 μM) |
|---|---|
| ln Vitro |
PBD-150 competitively inhibits human QC with a Ki of 0.06 μM. [1]
Molecular modeling shows that PBD-150 aligns with the substrate H-Gln-Phe-Ala-NH2; the imidazole nitrogen coordinates the catalytic zinc ion, and the aromatic moiety interacts with a hydrophobic pocket. [1] In [3], PBD-150 inhibits sQC with Ki = 0.095 μM and gQC with Ki = 1.817 μM. [3] X-ray crystal structure of hQC-2X-PBD-150 complex reveals that the imidazole N atom coordinates the zinc ion, replacing a water molecule; the thioketone S atom hydrogen-bonds to the backbone NH of Gln304; the aromatic terminal portion interacts with Phe325 via π-π stacking; the methoxy O atom makes a water-mediated interaction. [2] In gQC, PBD-150 binding induces a large loop movement (Lys229-Lys234) bringing Trp231 to interact with the propyl chain; the sulfur atom hydrogen-bonds to Gln325-N; the phenyl ring stacks with Phe346 and contacts Trp350 and Val324. [3] |
| ln Vivo |
The learning and memory capacities of transgenic mice models of Alzheimer's disease can be markedly enhanced by PBD-150 by reducing the accumulation of pyroglutamate-modified amyloid beta peptide in their brains [3].
|
| Enzyme Assay |
QC activity was measured fluorometrically using a coupled assay with Gln-AMC as substrate and pyroglutamyl peptidase as auxiliary enzyme. The released AMC was detected at excitation/emission 380/460 nm at 30°C. The assay mixture contained varying substrate concentrations (0.25-4×Km), different inhibitor concentrations, pyroglutamyl peptidase (0.1 U/mL), and QC (0.12 μg/mL) in 0.05 M Tris-HCl pH 8.0. After 10 min pre-incubation, the reaction was started by addition of QC. Inhibition constants were calculated by fitting progress curves to the competitive inhibition equation using GraFit software. [1]
Alternatively, QC activity was assayed at 25°C using the fluorescent substrate L-glutaminyl 2-naphthylamide (Gln-βNA). The reaction mixture (100 μL) contained 250 μM Gln-βNA, ~0.2 units of human pyroglutamyl aminopeptidase I, and diluted QC in 50 mM Tris-HCl, 5% glycerol pH 8.0. Fluorescence was measured at excitation 320 nm and emission 410 nm. The reaction was initiated by addition of QC. For inhibition assays, the enzyme was pre-incubated with the inhibitor for 5 min at 25°C before adding to the reaction mixture. IC50 values were obtained by fitting initial rates vs inhibitor concentrations, and Ki values were calculated using the equation IC50 = Ki (1 + S/Km). [3] |
| References |
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| Additional Infomation |
PBD-150 (compound 53 in [1]) was identified as the most potent inhibitor among a series of thiourea derivatives, with a Ki of 60 nM. [1]
The crystal structure of human secretory QC (sQC) in complex with PBD-150 was determined (PDB: 3PB8 in [3]). The structure of Golgi-resident QC (gQC) in complex with PBD-150 was also determined (PDB: 3PB7 in [3]). [3] The soluble variant hQC-2X (Y115E-Y117E) in complex with PBD-150 was crystallized and the structure solved at 1.95 Å resolution (PDB: 4ywy in [2]). [2] PBD-150 binds to the active site zinc ion via its imidazole nitrogen, replacing the catalytic water molecule. The thiourea sulfur forms a hydrogen bond with the backbone NH of Gln304 (or Gln325 in gQC). The dimethoxyphenyl ring engages in hydrophobic interactions with Phe325/Phe346 and Trp350. [2][3] |
| Molecular Formula |
C15H20N4O2S
|
|---|---|
| Molecular Weight |
320.409901618958
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| Exact Mass |
320.13
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| CAS # |
790663-33-1
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| PubChem CID |
6539196
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| Appearance |
Light brown to brown solid powder
|
| LogP |
1.5
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
22
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| Complexity |
346
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S=C(NCCCN1C=CN=C1)NC1C=C(OC)C(OC)=CC=1
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| InChi Key |
FZQXMGLQANXZRP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H20N4O2S/c1-20-13-5-4-12(10-14(13)21-2)18-15(22)17-6-3-8-19-9-7-16-11-19/h4-5,7,9-11H,3,6,8H2,1-2H3,(H2,17,18,22)
|
| Chemical Name |
1-(3,4-dimethoxyphenyl)-3-(3-imidazol-1-ylpropyl)thiourea
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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 : ~125 mg/mL (~390.13 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1210 mL | 15.6050 mL | 31.2100 mL | |
| 5 mM | 0.6242 mL | 3.1210 mL | 6.2420 mL | |
| 10 mM | 0.3121 mL | 1.5605 mL | 3.1210 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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