| 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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| Other Sizes |
| Targets |
The fascin-1 bundling activity is inhibited by BDP-13176 (0-1 μM) [1].
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|---|---|
| ln Vitro |
The fascin-1 bundling activity is inhibited by BDP-13176 (0-1 μM) [1].
BDP-13176 inhibited fascin-mediated bundling of filamentous actin (F-actin) in a biochemical assay with an IC50 of 240 ± 0.01 nM.[1] The compound exhibited favorable physicochemical properties: low lipophilicity (LogD7.4 = 1.8) and reasonable kinetic solubility (midpoint = 65 µM).[1] It demonstrated moderate stability in human and mouse liver microsomes (Human Clint = 6.4 µL/min/mg protein; Mouse Clint = 11.8 µL/min/mg protein).[1] Caco-2 permeability assay showed low permeability (A-B Papp = 0.15 x 10-6 cm/s) and high efflux (efflux ratio = 37.8).[1] |
| Enzyme Assay |
The binding affinity of BDP-13176 for fascin was determined using Surface Plasmon Resonance (SPR). Serial dilutions of the compound were injected over a fascin-immobilized chip, and the equilibrium dissociation constant (Kd) was calculated from the sensorgram data, yielding a Kd of 85 ± 0.02 nM.[1]
Isothermal Titration Calorimetry (ITC) was also used to confirm binding, where aliquots of the compound were titrated into a fascin solution, and the heat change was measured to determine the Kd, which was 50 nM.[1] A fluorescence-based in vitro F-actin bundling assay was developed to measure functional inhibition. Fascin was incubated with pre-polymerized, pyrene-labeled F-actin in the presence of varying concentrations of BDP-13176. The decrease in fluorescence due to bundling (and subsequent sedimentation) was monitored, and the concentration causing 50% inhibition (IC50) was calculated.[1] |
| ADME/Pharmacokinetics |
BDP-13176 exhibited low lipophilicity, with a measured LogD7.4 value of 1.8. [1]
Its kinetic solubility was determined to be 65 µM (midpoint). [1] Its in vitro metabolic stability was evaluated in human and mouse liver microsomes, showing moderate intrinsic clearance (human liver microsome intrinsic clearance = 6.4 µL/min/mg protein; mouse liver microsome intrinsic clearance = 11.8 µL/min/mg protein). [1] Its permeability was evaluated using a Caco-2 cell monolayer model. The apparent permeability from the apex to the outer side of the basement (AB Papp) was low at 0.15 x 10-6 cm/s, and the compound exhibited high efflux, with an efflux ratio of 37.8. [1] |
| References | |
| Additional Infomation |
Fascin is an actin bundler that is overexpressed in aggressive cancers and promotes cell migration and invasion. Inhibition of Fascin is a potential anti-metastatic strategy. [1]
BDP-13176 was developed from a fragment lead compound through structure-based drug design. It binds in the inducible pocket between the first two β-trefoil domains of Fascin, resulting in a significant conformational change in domain 1. This change is thought to deform the actin-binding region of Fascin, thereby disrupting its bundler activity. [1] This compound provides a promising starting point for the development of therapies targeting Fascin. [1] |
| Molecular Formula |
C24H22CL2N6O2
|
|---|---|
| Molecular Weight |
497.3765
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| Exact Mass |
496.12
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| Elemental Analysis |
C, 57.96; H, 4.46; Cl, 14.25; N, 16.90; O, 6.43
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| CAS # |
2290660-61-4
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| PubChem CID |
137333984
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| Appearance |
Solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
785
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BMOUOZDRMBLNSI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H22Cl2N6O2/c25-20-2-1-15(11-21(20)26)13-31-14-19(23(33)30-16-3-7-27-8-4-16)22-18(24(31)34)12-29-32(22)17-5-9-28-10-6-17/h1-4,7-8,11-12,14,17,28H,5-6,9-10,13H2,(H,27,30,33)
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| Chemical Name |
5-[(3,4-dichlorophenyl)methyl]-4-oxo-1-piperidin-4-yl-N-pyridin-4-ylpyrazolo[4,3-c]pyridine-7-carboxamide
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| Synonyms |
BDP 13176; BDP-13176; BDP13176;
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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 (~251.32 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.18 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 (4.18 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (4.18 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 | 2.0105 mL | 10.0527 mL | 20.1054 mL | |
| 5 mM | 0.4021 mL | 2.0105 mL | 4.0211 mL | |
| 10 mM | 0.2011 mL | 1.0053 mL | 2.0105 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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