TLR9-IN-1 is a novel selective TLR9 inhibitor with the potential to be used for diseases associated with undesirable immune response. It inhibits TLR9 with an IC50 value of 7 nM for human TLR9.
Physicochemical Properties
| Molecular Formula | C23H31N7O |
| Molecular Weight | 421.53854393959 |
| Exact Mass | 421.259 |
| CAS # | 2226366-86-3 |
| PubChem CID | 134515962 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.1 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 31 |
| Complexity | 572 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N1(C2=NN=CC3=CN(C4=CC=C(C)C=C4)N=C23)CCC(C(NCCCN(C)C)=O)CC1 |
| InChi Key | FRMXKWKQIYLSMO-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H31N7O/c1-17-5-7-20(8-6-17)30-16-19-15-25-26-22(21(19)27-30)29-13-9-18(10-14-29)23(31)24-11-4-12-28(2)3/h5-8,15-16,18H,4,9-14H2,1-3H3,(H,24,31) |
| Chemical Name | N-[3-(dimethylamino)propyl]-1-[2-(4-methylphenyl)pyrazolo[3,4-d]pyridazin-7-yl]piperidine-4-carboxamide |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | When coupled with the TLR8 agonist ORN8L and incubated with RNA oligonucleotide acid, TLR9-IN-1 (Compound No. 29) (0-10 μM; 24 hours) demonstrates modest inhibitory effect against IL-1b in human monocytes, with an IC50 of 1.61 μM [1]. |
| References |
[1]. Toll-like receptor antagonist compounds and methods of use. WO2018089695. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~500 mg/mL (~1186.13 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 12.5 mg/mL (29.65 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 125.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 12.5 mg/mL (29.65 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 125.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3723 mL | 11.8613 mL | 23.7225 mL | |
| 5 mM | 0.4745 mL | 2.3723 mL | 4.7445 mL | |
| 10 mM | 0.2372 mL | 1.1861 mL | 2.3723 mL |