| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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Purity: ≥98%
LY3000328 is a novel, potent and selective Cathepsin S (Cat S) inhibitor with IC50s of 7.7 and 1.67 nM for hCat S and mCat S, respectively. It has excellent in vitro potency and selectivity against other cysteine proteases. LY3000328 is currently in clinical trials. Cathepsin S (Cat S) plays an important role in many pathological conditions, including abdominal aortic aneurysm (AAA). Inhibition of Cat S may provide a new treatment for AAA.
| ln Vitro |
Excellent in vitro potency and selectivity are maintained by LY 3000328. LY 3000328 demonstrates low in vitro metabolism in mouse, rat, dog, and human liver microsomes (after 30 min incubation at 4 μM <20%); excellent permeability (MDCK AB>4%); and low in vitro CYP450 inhibition (CYP3A4, CYP2D6, and CYP2C9 at 10 μM <15%). Merely 6% displacement of [3H]-astemizole was seen in experiments employing HEK293 membrane preparations at a dosage of 100 μM for LY 3000328, suggesting a poor potential for hERG blocking [1]. A strong and selective inhibitor of cathepsin S (CatS) is LY 3000328. The inhibition of CatS activity in plasma is 50% of the maximum activity when the concentration of LY 3000328 in plasma is roughly 60 ng/mL [2].
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| ln Vivo |
LY 3000328's effectiveness was investigated using a mouse model of abdominal aortic aneurysm (AAA). In this model, peritoneal surface application of CaCl2 induces inflammation. The findings suggest that this model's disease state features are comparable to those of human AAA. At 1, 3, 10, and 30 mg/kg, LY 3000328 showed a dose-responsive decrease in aortic diameter. Aortic diameter was lowered by 58% at the lowest dosage of LY 3000328—1 mg/kg—83% at 3 mg/kg, and 87% at 10 mg/kg. Good drug disposal properties of LY 3000328 were indicated by the dose-dependent increase in exposure (AUC) of both compounds [1].
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| References |
| Molecular Formula |
C24H28N2O5.H2O
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|---|---|
| Molecular Weight |
442.505
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| Exact Mass |
484.212
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| CAS # |
1373215-15-6
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| PubChem CID |
67475270
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
701.6±60.0 °C at 760 mmHg
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| Flash Point |
378.1±32.9 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.639
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| LogP |
1.44
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
739
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CNC(=O)O[C@H]1COC2=C([C@@H]1NC(=O)C3=CC=C(C=C3)F)C=C(C=C2)N4CCN(CC4)C5COC5
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| InChi Key |
NDEBZCZEAVMSQF-GOTSBHOMSA-N
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| InChi Code |
InChI=1S/C25H29FN4O5/c1-27-25(32)35-22-15-34-21-7-6-18(29-8-10-30(11-9-29)19-13-33-14-19)12-20(21)23(22)28-24(31)16-2-4-17(26)5-3-16/h2-7,12,19,22-23H,8-11,13-15H2,1H3,(H,27,32)(H,28,31)/t22-,23-/m0/s1
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| Chemical Name |
(3R,4S)-4-(4-fluorobenzamido)-6-(4-(oxetan-3-yl)piperazin-1-yl)chroman-3-yl methylcarbamate
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| Synonyms |
LY3000328; LY-3000328; LY 3000328
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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 : ≥ 50 mg/mL (~103.19 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.16 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 25.0 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: ≥ 2.5 mg/mL (5.16 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 25.0 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: ≥ 2.5 mg/mL (5.16 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 | 2.2598 mL | 11.2992 mL | 22.5984 mL | |
| 5 mM | 0.4520 mL | 2.2598 mL | 4.5197 mL | |
| 10 mM | 0.2260 mL | 1.1299 mL | 2.2598 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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