YKL-06-061 (YKL06-061) is a novel and potent SIK (salt-inducible kinase) inhibitor (IC50: 6.56 nM/1.77 nM/20.5 nM (SIK1/2/3)) with the potential to be used as a dermatologic drug impacting UV protection and skin cancer risk. It causes a dose-dependent increase in microphthalmia-associated transcription factor (MITF) mRNA expression during 3-hour function in normal human melanocytes, UACC62 human melanoma cells, and UACC257 human melanoma cells.
Physicochemical Properties
| Molecular Formula | C30H37N7O2 |
| Molecular Weight | 527.660485982895 |
| Exact Mass | 527.3 |
| CAS # | 2172617-15-9 |
| PubChem CID | 132992144 |
| Appearance | White to off-white solid powder |
| LogP | 4.5 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 39 |
| Complexity | 824 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1N(C2C(C)=CC=CC=2C)CC2=CN=C(NC3C=CC(=CC=3OC)N3CCN(C)CC3)N=C2N1C1CCC1 |
| InChi Key | GVBAXIVNAHMIGH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C30H37N7O2/c1-20-7-5-8-21(2)27(20)36-19-22-18-31-29(33-28(22)37(30(36)38)23-9-6-10-23)32-25-12-11-24(17-26(25)39-4)35-15-13-34(3)14-16-35/h5,7-8,11-12,17-18,23H,6,9-10,13-16,19H2,1-4H3,(H,31,32,33) |
| Chemical Name | 1-cyclobutyl-3-(2,6-dimethylphenyl)-7-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-4H-pyrimido[4,5-d]pyrimidin-2-one |
| Synonyms | YKL 06-061 YKL06-061 YKL-06-061 |
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 | YKL 06-061 increases the expression of MITF mRNA in a dose-dependent manner [1]. |
| Cell Assay |
RT-PCR[1] Cell Types: UACC62 human melanoma cells and UACC257 human melanoma cells. Tested Concentrations: 0-4μM (UACC62); 0-16 μM (UACC257). Incubation Duration: 3 hrs (hours). Experimental Results: MITF mRNA expression increased in a dose-dependent manner. |
| References |
[1]. A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin. Cell Rep. 2017 Jun 13;19(11):2177-2184. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~16.67 mg/mL (~31.59 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.37 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 12.5 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: ≥ 1.25 mg/mL (2.37 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 12.5 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 | 1.8952 mL | 9.4758 mL | 18.9516 mL | |
| 5 mM | 0.3790 mL | 1.8952 mL | 3.7903 mL | |
| 10 mM | 0.1895 mL | 0.9476 mL | 1.8952 mL |