Physicochemical Properties
| Molecular Formula | C30H31FN4O3 |
| Molecular Weight | 514.59 |
| Exact Mass | 514.238 |
| CAS # | 2408842-51-1 |
| PubChem CID | 146014479 |
| Appearance | Light yellow to brown solid powder |
| LogP | 4.1 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 38 |
| Complexity | 874 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N1(C)C=CN(CC2=CC(=C3C(C(=O)C(CC4C=C(OC)C=C(OC)C=4)CC3)=C2)C2=C(C=C(C=C2)F)C)C1=N |
| InChi Key | PKONCIPMLLIAIL-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C30H31FN4O3/c1-19-11-22(31)5-6-25(19)27-14-21(18-35-10-9-33(2)30(35)32)15-28-26(27)7-8-34(29(28)36)17-20-12-23(37-3)16-24(13-20)38-4/h5-6,9-16,32H,7-8,17-18H2,1-4H3 |
| Chemical Name | 2-[(3,5-dimethoxyphenyl)methyl]-5-(4-fluoro-2-methylphenyl)-7-[(2-imino-3-methylimidazol-1-yl)methyl]-3,4-dihydroisoquinolin-1-one |
| Synonyms | WDR5IN1 WDR5 IN 1 |
| 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 |
| 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 | G2M phase cells are significantly reduced in WDR5-IN-1 (1 μM; 48 hours) [1]. WDR5-IN-1 (0.01-3 μM; 24-48 hours) raises the levels of the proteins p53 and p21 [1]. With a GI50 range of 0.26-3.2 μM, IN-1 demonstrates anti-proliferative efficacy in MYC-driven malignancies (CHP-134, Ramos, Raji, Daudi, SW620, and SW480 cells) [1]. |
| Cell Assay |
Cell Cycle Analysis[1] Cell Types: MV4:11 Cell Tested Concentrations: 1 µM Incubation Duration: 48 hrs (hours) Experimental Results: demonstrated an approximately 4-fold increase in SubG1 cells. Western Blot Analysis[1] Cell Types: MV4:11 Cell Tested Concentrations: 0.01, 0.03, 0.1, 0.3, 1, 3 µM Incubation Duration: 24, 48 hrs (hours) Experimental Results: p53 and p21 protein levels increased starting from 8 hrs (hours) after treatment with Compound 16 The concentration was 300 nM and continued to increase until 32 hrs (hours). |
| References |
[1]. Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core.J Med Chem. 2020 Jan 23;63(2):656-675. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~194.33 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.86 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 (4.86 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9433 mL | 9.7165 mL | 19.4329 mL | |
| 5 mM | 0.3887 mL | 1.9433 mL | 3.8866 mL | |
| 10 mM | 0.1943 mL | 0.9716 mL | 1.9433 mL |