Physicochemical Properties
| Molecular Formula | C??H??CLF?N?O?S |
| Molecular Weight | 661.08 |
| Appearance | White to light yellow solid powder |
| Synonyms | Dot1LIN4; Dot1L IN 4 |
| 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 | In cellular experiments, Dot1L-IN-4 (Compound 10) is evaluated for its capacity to suppress HOXA9 gene expression in Molm-13 cells (ED50 HOXA9 RGA=33 nM) and the dimethylation of H3K79 in HeLa cells (ED50 H3K79me2 Elisa=1.7 nM). With an IC50 of 99 µM, dot1L-IN-4 also suppresses mixed lineage leukemia (MLL)[1]. |
| ln Vivo | Tumor xenograft bearing mice do not tolerate Dot1L-IN-4 (Compound 10; 300 mg/kg; po; qd) at such large doses, and at a 6-fold decreased dose, the tumor development as well as the HOXA9 reporter gene mRNA are reduced by less than half in comparison to control animals[1]. |
| Animal Protocol |
Animal/Disease Models: Male mice (C57BL/6) bearing subcutaneous (sc) MV4-11 tumor xenografts[1] Doses: 300 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: Po Experimental Results: Was not tolerated at such a high dose by tumor xenograft bearing mice, and at a 6-fold decreased dose, the tumor growth as well as the HOXA9 reporter gene mRNA were decreased only by less than half as compared to control animals. |
| References |
[1]. New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse. ACS Med. Chem. Lett. 2019, 10, 12, 1655-1660. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.15 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 20.8 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: 2.08 mg/mL (3.15 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5127 mL | 7.5634 mL | 15.1268 mL | |
| 5 mM | 0.3025 mL | 1.5127 mL | 3.0254 mL | |
| 10 mM | 0.1513 mL | 0.7563 mL | 1.5127 mL |