Y06036 is a potent BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). Y06036 bounds to the BRD4(1) bromodomain with Kd values of 82 nM. Y06036 also exhibited high selectivity over other non-BET subfamily members. Y06036 potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Y06036 also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice.
Physicochemical Properties
| Molecular Formula | C16H15BRN2O5S |
| Molecular Weight | 427.269702196121 |
| Exact Mass | 425.988 |
| CAS # | 1832671-96-1 |
| Related CAS # | 1832671-96-1; |
| PubChem CID | 134159768 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 3.3 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 25 |
| Complexity | 557 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | BrC1C=CC(=C(C=1)S(NC1C(=CC2=C(C(C)=NO2)C=1)OC)(=O)=O)OC |
| InChi Key | KVGNGFGTOSOVPB-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C16H15BrN2O5S/c1-9-11-7-12(15(23-3)8-14(11)24-18-9)19-25(20,21)16-6-10(17)4-5-13(16)22-2/h4-8,19H,1-3H3 |
| Chemical Name | 5-Bromo-2-methoxy-N-(6-methoxy-3-methylbenzo[d]-isoxazol-5-yl)benzenesulfonamide |
| Synonyms | Y06036 Y-06036 Y 06036. |
| 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 | The prostate cancer cell lines LNCaP, C4-2B, 22Rv1, and VCaP show low micromolar or nanomolar potency (IC50: 0.29-2.6 μM) when exposed to Y06036 (0.001-100 nM, 96 hr for LNCaP, C4-2B, and 22Rv1 cells; 144 hr for VCaP cells). Y06036 (1, 2, 4, 8 and 16 μM) treatment for 48 hours significantly reduced the levels of both full-length (AR-fl) and AR variants in 22Rv1 cells [1]. |
| ln Vivo | A mouse C4-2B CRPC xenograft tumor model demonstrated the therapeutic efficacy of Y06036 (50 mg/kg, i.p., five times per week for 25 days). Based on the mice's overall behavior and body weight, Y06036 was well tolerated in treated animals [1]. |
| Cell Assay |
Cell viability assay[1] Cell Types: LNCaP, C4-2B, 22Rv1 and VCaP Prostate cancer cell Tested Concentrations: 0.001-100 μM Incubation Duration: 96 hrs (hours) for LNCaP, C4-2B and 22Rv1; 144 hrs (hours) for VCaP Experimental Results: Inhibition of LNCaP, C4 -2B, 22Rv1 and VCaP cells, IC50 are 1.06, 2.62, 1.50 and 0.63 μM respectively. Western Blot Analysis[1] Cell Types: 22Rv1 Cell Tested Concentrations: 1, 2, 4, 8 and 16 μM Incubation Duration: 48 hrs (hours) Experimental Results: Result in significant downregulation of AR-fl and AR variant levels |
| Animal Protocol |
Animal/Disease Models: 4weeks old male mice (strain: CB-17/IcrHsd-Prkdcscid for C4-2B), C4-2B mouse xenograft model [1] Doses: 50 mg/kg, 100 μL Route of Administration: peritoneal intravenous (iv) (iv)(i.p.) injection, 5 times per week for 25 days. Experimental Results: Demonstrated strong anti-tumor activity with a tumor growth inhibition (TGI) of 70% during the 25-day treatment period. |
| References |
[1]. Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). J Med Chem. 2018 Apr 12;61(7):3037-3058. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~130 mg/mL (~304.26 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (5.08 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 21.7 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: ≥ 2.17 mg/mL (5.08 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 21.7 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 | 2.3404 mL | 11.7022 mL | 23.4044 mL | |
| 5 mM | 0.4681 mL | 2.3404 mL | 4.6809 mL | |
| 10 mM | 0.2340 mL | 1.1702 mL | 2.3404 mL |