| 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 |
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| Other Sizes |
Purity: ≥98%
| Targets |
BI-409306 (CAS#: 1189767-28-9) targets human PDE9A (IC50 = 65 ± 11 nM), rat PDE9A (IC50 = 168 nM), human PDE1A (IC50 = 1.45 μM), human PDE1C (IC50 = 1.17 μM). No inhibitory activity (IC50 > 10 μM) against human PDE2A, 3A, 4B, 5A, 6AB, 7A, and 10A. [1]
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| ln Vitro |
Osoresnontrine is a potent and selective PDE9A inhibitor, with an IC50 of 52 nM, and shows weak activity against other PDEs, such as PDE1A (IC50, 1.4 µM), PDE1C (IC50, 1.0 µM), PDE2A, PDE3A, PDE4B, PDE5A, PDE6AB, PDE7A, and PDE10A (IC50 all > 10 μM), and has no obvious effect on 95 non-PDE targets at 10 μM. Osoresnontrine improves long-term potentiation (LTP) in rat hippocampus slices[1].
BI-409306 (CAS#: 1189767-28-9) is a potent and selective inhibitor of PDE9A in vitro, with mean IC50 of 65 nM for human PDE9A and 168 nM for rat PDE9A. It shows weak inhibition of PDE1A (1.45 μM) and PDE1C (1.17 μM), and no inhibition (IC50 >10 μM) of PDE2A, 3A, 4B, 5A, 6AB, 7A, and 10A. It has no significant activity against 95 non-PDE targets at 10 μM. [1] |
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| ln Vivo |
BI-409306 (CAS#: 1189767-28-9) increases cGMP levels in rat prefrontal cortex and cerebrospinal fluid (CSF) in a dose-dependent manner after intraperitoneal or oral administration. At 7.5 mg/kg i.p., it increased extracellular cGMP by 187.9% at 20 min; at 15 mg/kg i.p., significant increases at 20, 40, and 180 min. Oral administration at 3 and 10 mg/kg significantly increased cGMP in rat CSF (p<0.001). It reverses MK-801-induced reduction in mouse striatal cGMP: 0.5 mg/kg i.p. significantly attenuated the decrease (41% increase vs MK-801 alone, p<0.01). [1]
It enhances hippocampal long-term potentiation (LTP) ex vivo in rat slices: at 1 μM (bath-applied) enhances LTP induced by weak tetanic stimulation (p=0.021); at 0.3 μM enhances LTP induced by strong tetanic stimulation (p=0.048). [1] It improves working memory in mice: oral BI 409306 (0.007-2.5 mg/kg) reverses MK-801-induced deficit in T-maze spontaneous alternation (p<0.05). It improves episodic memory: i.p. 0.15 mg/kg (30 min before trial 1) significantly increases novel object exploration time 24 h later (p<0.001). [1] |
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| Enzyme Assay |
In vitro potency and selectivity were determined using scintillation proximity assays (SPA) for PDE inhibition. Recombinant human and rat PDE isoforms were expressed in SF9 insect cells via baculovirus system. Cell extracts containing PDE were incubated with serial dilutions of BI-409306 (CAS#: 1189767-28-9) in assay buffer (50 mM Tris pH 7.4, 8.3 mM MgCl2, 1.7 mM EGTA, 0.1% BSA, 0.05% Tween-20). For PDE1A/1C, 200 nM calmodulin and 12 mM CaCl2 were added. The reaction was initiated by adding 80 nM ³H-cGMP or ³H-cAMP (1 mCi/L) and incubated 1 h at room temperature. The reaction was stopped with 50 μM inhibitor solution and 17.9 mg/ml yttrium silicate SPA beads. Conversion of substrate was measured by scintillation counting. IC50 values were calculated using GraphPad Prism. Selectivity against non-PDE targets was assessed by receptor binding assays at MDS Pharma Services. [1]
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| Animal Protocol |
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| ADME/Pharmacokinetics |
After oral administration of BI-409306 (CAS#: 1189767-28-9) at 1.5 mg/kg in rats: mean plasma concentrations (n=3) were 892 nM at 0.5 h, 714 nM at 1 h, 683 nM at 2 h, 50 nM at 4 h. In mice (NMRI, 20-25 g) at same dose: 2097 nM at 0.5 h, 2227 nM at 1 h, 1042 nM at 2 h, 183 nM at 4 h. CSF concentration of BI 409306 was approximately 20% of plasma concentration (from separate study). [1]
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| References | |||
| Additional Infomation |
Osoresnontrine is being investigated in the clinical trial NCT02281773 (a study designed to investigate the efficacy, safety, and tolerability of four different doses of BI 409306 compared to placebo in patients with schizophrenia receiving stable antipsychotic medication over a 12-week period).
BI-409306 (CAS#: 1189767-28-9) is a PDE9A inhibitor developed by Boehringer Ingelheim. It has been evaluated in phase I and phase II clinical trials for cognitive impairment in schizophrenia and Alzheimer's disease. CSF cGMP levels are a translatable biomarker of target engagement. The compound enhances both early and late-phase LTP, suggesting promotion of protein synthesis-dependent long-term memory consolidation. [1] |
| Molecular Formula |
C16H17N5O2
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| Molecular Weight |
311.338482618332
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| Exact Mass |
311.138
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| CAS # |
1189767-28-9
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| Related CAS # |
1189767-28-9;
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| PubChem CID |
135908617
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| Appearance |
White to off-white solid powder
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| LogP |
0.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
477
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1CCC(CC1)N1C2=C(C(NC(CC3C=CC=CN=3)=N2)=O)C=N1
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| InChi Key |
BZTIJCSHNVZMES-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H17N5O2/c22-16-13-10-18-21(12-4-7-23-8-5-12)15(13)19-14(20-16)9-11-3-1-2-6-17-11/h1-3,6,10,12H,4-5,7-9H2,(H,19,20,22)
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| Chemical Name |
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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) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.03 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 (8.03 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 saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (8.03 mM) 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 | 3.2119 mL | 16.0596 mL | 32.1192 mL | |
| 5 mM | 0.6424 mL | 3.2119 mL | 6.4238 mL | |
| 10 mM | 0.3212 mL | 1.6060 mL | 3.2119 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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