BMS-751324 is a clinical prodrug of p38α MAP kinase inhibitor. BMS-751324 is prodrug of BMS-582949. BMS-751324 was designed to address the issue of pH-dependent solubility and exposure associated with BMS-582949, a phase II clinical p38α MAP kinase inhibitor. BMS-751324 is featured with a carbamoylmethylene linked promoiety containing hydroxyphenyl acetic acid (HPA) derived ester and phosphate functionalities. BMS-751324 was not only stable but also water-soluble under both acidic and neutral conditions. BMS-751324 was effectively bioconverted into parent drug BMS-582949 in vivo by alkaline phosphatase and esterase in a stepwise manner, providing higher exposure of BMS-582949 compared to its direct administration, especially within higher dose ranges. In a rat LPS-induced TNFα pharmacodynamic model and a rat adjuvant arthritis model, BMS-751324 demonstrated similar efficacy to BMS-582949. Most importantly, it was shown in clinical studies that prodrug BMS-582949 was indeed effective in addressing the pH-dependent absorption issue associated with BMS-582949.
MedKoo Cat#: 522407
Name: BMS-751324
CAS#: 948842-66-8
Chemical Formula: C32H35N6O10P
Exact Mass: 694.2152
Molecular Weight: 694.64
Elemental Analysis: C, 55.33; H, 5.08; N, 12.10; O, 23.03; P, 4.46
The following data is based on the product molecular weight 694.64 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
