WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 522407
Description: 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
Chemical Formula: C32H35N6O10P
Exact Mass: 694.21523
Molecular Weight: 694.64
Elemental Analysis: C, 55.33; H, 5.08; N, 12.10; O, 23.03; P, 4.46
Synonym: BMS-751324; BMS 751324; BMS751324.
IUPAC/Chemical Name: (((4-((5-(cyclopropylcarbamoyl)-2-methylphenyl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carbonyl)(propyl)carbamoyl)oxy)methyl 2-(4-(phosphonooxy)phenyl)acetate
InChi Key: XAYQDTPEOFCYIG-UHFFFAOYSA-N
InChi Code: InChI=1S/C32H35N6O10P/c1-4-13-37(32(42)47-18-46-27(39)14-21-6-11-24(12-7-21)48-49(43,44)45)31(41)25-16-38-28(20(25)3)29(33-17-34-38)36-26-15-22(8-5-19(26)2)30(40)35-23-9-10-23/h5-8,11-12,15-17,23H,4,9-10,13-14,18H2,1-3H3,(H,35,40)(H,33,34,36)(H2,43,44,45)
SMILES Code: CC1=CC=C(C(NC2CC2)=O)C=C1NC3=NC=NN4C3=C(C(C(N(CCC)C(OCOC(CC(C=C5)=CC=C5OP(O)(O)=O)=O)=O)=O)=C4)C
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
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|
1: Liu C, Lin J, Hynes J, Wu H, Wrobleski ST, Lin S, Dhar TG, Vrudhula VM, Sun
JH, Chao S, Zhao R, Wang B, Chen BC, Everlof G, Gesenberg C, Zhang H, Marathe PH,
McIntyre KW, Taylor TL, Gillooly K, Shuster DJ, McKinnon M, Dodd JH, Barrish JC,
Schieven GL, Leftheris K. Discovery of
(BMS-751324), a Clinical Prodrug of p38α MAP Kinase Inhibitor. J Med Chem. 2015
Sep 22. [Epub ahead of print] PubMed PMID: 26359680.
2: Saxena A, Shah D, Padmanabhan S, Gautam SS, Chowan GS, Mandlekar S, Desikan S.
Prediction of pH dependent absorption using in vitro, in silico, and in vivo rat
models: Early liability assessment during lead optimization. Eur J Pharm Sci.
2015 Aug 30;76:173-80. doi: 10.1016/j.ejps.2015.05.006. Epub 2015 May 8. PubMed