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| 5mg |
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| Targets |
RO5508887 targets beta-secretase 1 (BACE1) and beta-secretase 2 (BACE2), the enzymes responsible for the cleavage of amyloid precursor protein (APP) to generate amyloid-β (Aβ) peptides. By inhibiting BACE1, RO5508887 reduces the production of Aβ peptides, which are the primary components of amyloid plaques in Alzheimer's disease. It is a potent and selective BACE inhibitor.
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| ln Vitro |
RO5508887 is a potent inhibitor of BACE1 and BACE2 with IC50 values of 30-32 nM for BACE1 and 40-47 nM for BACE2. It is a BBB-penetrant compound, meaning it can cross the blood-brain barrier to reach its target in the brain. This makes it a valuable tool for studying the role of BACE1 in Alzheimer's disease.
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| ln Vivo |
RO5508887 has been evaluated in clinical trials. A pharmacodynamic and pharmacokinetic study of RO5508887 was conducted in healthy volunteers (ClinicalTrials.gov NCT01592331). This suggests that the compound has been advanced to clinical development for the potential treatment of Alzheimer's disease. Specific in vivo efficacy data in animal models is not detailed in the available literature.
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| Enzyme Assay |
The in vitro activity of RO5508887 is assessed using enzyme inhibition assays with purified recombinant BACE1 and BACE2. The compound is incubated with the enzyme and a fluorogenic peptide substrate, and the extent of inhibition is measured. The IC50 values of 30-32 nM for BACE1 and 40-47 nM for BACE2 are determined from these assays.
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| Cell Assay |
Cell-based assays are used to evaluate RO5508887's ability to inhibit Aβ production. Cells expressing human APP are treated with various concentrations of RO5508887, and the levels of Aβ peptides in the culture supernatant are measured by ELISA. The compound's ability to reduce Aβ production is assessed, and IC50 values for cellular activity are determined.
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| Animal Protocol |
RO5508887 has been evaluated in preclinical animal models of Alzheimer's disease. In these studies, the compound is typically administered orally or via other routes to transgenic mice expressing human APP. The effects on brain Aβ levels, plaque burden, and cognitive function are assessed. However, specific protocols are not detailed in the available literature.
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| ADME/Pharmacokinetics |
RO5508887 free base has a molecular weight of 389.33 and a molecular formula of C18H14F3N5O2. It appears as a white to off-white solid powder. The compound is soluble in DMSO (approximately 85 mg/mL). Powder should be stored at -20°C for up to 3 years, and in solvent at -80°C for 6 months or -20°C for 1 month. Purity is typically ≥98%.
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| Toxicity/Toxicokinetics |
RO5508887 is a research compound that has been advanced to clinical trials. Its safety profile has been evaluated in healthy volunteers in a Phase 1 study (NCT01592331). As a BACE inhibitor, potential mechanism-based toxicities may include effects on BACE2 function, which is involved in melanocyte pigmentation and other processes. Further clinical studies are needed to fully characterize its safety and efficacy.
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| References | |
| Additional Infomation |
RO5508887 free base (CAS#: 1310347-50-2) is a novel, BBB-penetrant and potent BACE inhibitor, also known as RG-7129 and BACE1-IN-1. It has IC50s of 30-32 nM for BACE1 and 40-47 nM for BACE2. RO5508887 has been studied in clinical trials for Alzheimer's disease (NCT01592331). It is a valuable research tool and potential therapeutic candidate for Alzheimer's disease.
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| Molecular Formula |
C18H14F3N5O2
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|---|---|
| Molecular Weight |
389.331273555756
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| Exact Mass |
389.109
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| CAS # |
1310347-50-2
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| Related CAS # |
1310347-50-2;1310349-35-9 (HCl);
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| PubChem CID |
53241828
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| Appearance |
White to off-white solid powder
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| LogP |
1.7
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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 |
3
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| Heavy Atom Count |
28
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| Complexity |
694
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1(C(NC2=CC=C(F)C([C@]3(C)C(F)(F)COC(N)=N3)=C2)=O)=NC=C(C#N)C=C1
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| InChi Key |
DVMUZHLUMHPCGZ-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C18H14F3N5O2/c1-17(18(20,21)9-28-16(23)26-17)12-6-11(3-4-13(12)19)25-15(27)14-5-2-10(7-22)8-24-14/h2-6,8H,9H2,1H3,(H2,23,26)(H,25,27)/t17-/m1/s1
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| Chemical Name |
N-[3-[(4R)-2-amino-5,5-difluoro-4-methyl-6H-1,3-oxazin-4-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide
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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 : ~85 mg/mL (~218.32 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 | 2.5685 mL | 12.8426 mL | 25.6852 mL | |
| 5 mM | 0.5137 mL | 2.5685 mL | 5.1370 mL | |
| 10 mM | 0.2569 mL | 1.2843 mL | 2.5685 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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