Y06137 (Y0-6137; Y0 6137)is a novel and potent bromodomain BET inhibitor (Kd = 81 nM.) with potential anticancer activity. It may be used for treatment of castration-resistant prostate cancer (CRPC).
Physicochemical Properties
| Molecular Formula | C27H32N4O2 |
| Molecular Weight | 444.568586349487 |
| Exact Mass | 444.252 |
| CAS # | 2226534-49-0 |
| PubChem CID | 137333445 |
| Appearance | White to off-white solid powder |
| LogP | 5.8 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 33 |
| Complexity | 658 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C[C@H]1COCCN1C2=CC3=C(C=C2)N=C(N3CC4CCCCC4)C5=CC6=C(C=C5)ON=C6C |
| InChi Key | JYCNBHVRGVCHIQ-SFHVURJKSA-N |
| InChi Code | InChI=1S/C27H32N4O2/c1-18-17-32-13-12-30(18)22-9-10-24-25(15-22)31(16-20-6-4-3-5-7-20)27(28-24)21-8-11-26-23(14-21)19(2)29-33-26/h8-11,14-15,18,20H,3-7,12-13,16-17H2,1-2H3/t18-/m0/s1 |
| Chemical Name | 5-[1-(cyclohexylmethyl)-6-[(3S)-3-methylmorpholin-4-yl]benzimidazol-2-yl]-3-methyl-1,2-benzoxazole |
| Synonyms | Y06137 Y0-6137Y0 6137 |
| 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 Y06137 (0.001-100 nM, 96 hr in LNCaP, C4-2B, and 22Rv1 cells; 144 hr in VCaP cells). Following a 48-hour treatment with Y06137 (1, 2, 4, 8, and 16 μM), full-length (AR-fl) and AR variant levels were significantly downregulated in 22Rv1 cells [1]. |
| ln Vivo | A mouse C4-2B CRPC xenograft tumor model was used to test the therapeutic efficacy of Y06137 (50 mg/kg, i.p., five times per week for 25 days). Based on the mice's overall body weight and behavior, Y06137 was well tolerated in treated mice [1]. |
| Cell Assay |
Cell viability assay [1] Cell Types: AR-positive prostate cancer cell lines LNCaP, C4-2B, 22Rv1 and VCaP 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 For LNCaP, C4-2B, 22Rv1 and VCaP cells, the IC50 is 0.47, 0.84, 0.70 and 0.29 μM respectively. Western Blot Analysis[1] Cell Types: AR-positive prostate cancer cell line 22Rv1 Tested Concentrations: 1, 2, 4, 8 and 16 μM Incubation Duration: 48 hrs (hours) Experimental Results: Resulted 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 during the 25-day treatment period, with a tumor growth inhibition (TGI) of 51%. |
| References | [1]. Zhang M, et al. 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 : ~62.5 mg/mL (~140.59 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.68 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 (4.68 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 | 2.2494 mL | 11.2468 mL | 22.4936 mL | |
| 5 mM | 0.4499 mL | 2.2494 mL | 4.4987 mL | |
| 10 mM | 0.2249 mL | 1.1247 mL | 2.2494 mL |