Synonym
BMS299897; BMS 299897; BMS-299897.
IUPAC/Chemical Name
(R)-4-(2-(1-(4-chloro-N-(2,5-difluorophenyl)phenylsulfonamido)ethyl)-5-fluorophenyl)butanoic acid
InChi Key
IZAOBRWCUGOKNH-OAHLLOKOSA-N
InChi Code
InChI=1S/C24H21ClF3NO4S/c1-15(21-11-7-18(26)13-16(21)3-2-4-24(30)31)29(23-14-19(27)8-12-22(23)28)34(32,33)20-9-5-17(25)6-10-20/h5-15H,2-4H2,1H3,(H,30,31)/t15-/m1/s1
SMILES Code
O=C(O)CCCC1=CC(F)=CC=C1[C@H](N(C2=CC(F)=CC=C2F)S(=O)(C3=CC=C(Cl)C=C3)=O)C
Appearance
white 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
Biological target:
BMS 299897 is a sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).
In vitro activity:
BMS-299897 was 15-fold more effective at preventing the cleavage of APP than of Notch in vitro.
Reference: J Pharmacol Exp Ther. 2005 Feb;312(2):635-43. https://pubmed.ncbi.nlm.nih.gov/15452193/
In vivo activity:
This study analyzed whether a γ-secretase inhibitor, BMS-299897, attenuated this Aβ(25-35)-induced Aβ(1-42) seeding and toxicity. Mice were submitted to spontaneous alternation, passive avoidance and object recognition to analyze their short- and long-term memory abilities. BMS-299897 blocked the increase in Aβ(1-42) content and decreased Aβ(1-40) levels significantly. Behaviorally, BMS-299897 blocked the Aβ(25-35)-induced deficits in spontaneous alternation or novel object recognition, using a 1h intertrial time interval.
Reference: Eur J Pharmacol. 2013 Jan 5;698(1-3):193-9. https://pubmed.ncbi.nlm.nih.gov/23123349/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
40.6 |
79.31 |
| Ethanol |
51.2 |
100.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
511.94
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 |
Formulation protocol:
1. Barten DM, Guss VL, Corsa JA, Loo A, Hansel SB, Zheng M, Munoz B, Srinivasan K, Wang B, Robertson BJ, Polson CT, Wang J, Roberts SB, Hendrick JP, Anderson JJ, Loy JK, Denton R, Verdoorn TA, Smith DW, Felsenstein KM. Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor. J Pharmacol Exp Ther. 2005 Feb;312(2):635-43. doi: 10.1124/jpet.104.075408. Epub 2004 Sep 27. PMID: 15452193.
2. Meunier J, Villard V, Givalois L, Maurice T. The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease. Eur J Pharmacol. 2013 Jan 5;698(1-3):193-9. doi: 10.1016/j.ejphar.2012.10.033. Epub 2012 Nov 2. PMID: 23123349.
3. Zheng M, Wang J, Lubinski J, Flint OP, Krishna R, Yao M, Pursley JM, Thakur A, Boulton DW, Santone KS, Barten DM, Anderson JJ, Felsenstein KM, Hansel SB. Studies on the pharmacokinetics and metabolism of a gamma-secretase inhibitor BMS-299897, and exploratory investigation of CYP enzyme induction. Xenobiotica. 2009 Jul;39(7):544-55. doi: 10.1080/00498250902928555. PMID: 19480557.
In vitro protocol:
1. Barten DM, Guss VL, Corsa JA, Loo A, Hansel SB, Zheng M, Munoz B, Srinivasan K, Wang B, Robertson BJ, Polson CT, Wang J, Roberts SB, Hendrick JP, Anderson JJ, Loy JK, Denton R, Verdoorn TA, Smith DW, Felsenstein KM. Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor. J Pharmacol Exp Ther. 2005 Feb;312(2):635-43. doi: 10.1124/jpet.104.075408. Epub 2004 Sep 27. PMID: 15452193.
In vivo protocol:
1. Meunier J, Villard V, Givalois L, Maurice T. The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease. Eur J Pharmacol. 2013 Jan 5;698(1-3):193-9. doi: 10.1016/j.ejphar.2012.10.033. Epub 2012 Nov 2. PMID: 23123349.
2. Zheng M, Wang J, Lubinski J, Flint OP, Krishna R, Yao M, Pursley JM, Thakur A, Boulton DW, Santone KS, Barten DM, Anderson JJ, Felsenstein KM, Hansel SB. Studies on the pharmacokinetics and metabolism of a gamma-secretase inhibitor BMS-299897, and exploratory investigation of CYP enzyme induction. Xenobiotica. 2009 Jul;39(7):544-55. doi: 10.1080/00498250902928555. PMID: 19480557.
1: Meunier J, Villard V, Givalois L, Maurice T. The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease. Eur J Pharmacol. 2013 Jan 5;698(1-3):193-9. doi: 10.1016/j.ejphar.2012.10.033. Epub 2012 Nov 2. PubMed PMID: 23123349.
2: Zheng M, Wang J, Lubinski J, Flint OP, Krishna R, Yao M, Pursley JM, Thakur A, Boulton DW, Santone KS, Barten DM, Anderson JJ, Felsenstein KM, Hansel SB. Studies on the pharmacokinetics and metabolism of a gamma-secretase inhibitor BMS-299897, and exploratory investigation of CYP enzyme induction. Xenobiotica. 2009 Jul;39(7):544-55. doi: 10.1080/00498250902928555. PubMed PMID: 19480557.
3: Xue YJ, Pursley J, Arnold M. Liquid-liquid extraction of strongly protein bound BMS-299897 from human plasma and cerebrospinal fluid, followed by high-performance liquid chromatography/tandem mass spectrometry. J Pharm Biomed Anal. 2007 Apr 11;43(5):1728-36. Epub 2007 Jan 3. PubMed PMID: 17204392.
4: Zhang D, Hanson R, Roongta V, Dischino DD, Gao Q, Sloan CP, Polson C, Keavy D, Zheng M, Mitroka J, Yeola S. In vitro and in vivo metabolism of a gamma-secretase inhibitor BMS-299897 and generation of active metabolites in milligram quantities with a microbial bioreactor. Curr Drug Metab. 2006 Dec;7(8):883-96. PubMed PMID: 17168689.
5: Anderson JJ, Holtz G, Baskin PP, Turner M, Rowe B, Wang B, Kounnas MZ, Lamb BT, Barten D, Felsenstein K, McDonald I, Srinivasan K, Munoz B, Wagner SL. Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897. Biochem Pharmacol. 2005 Feb 15;69(4):689-98. Epub 2005 Jan 7. PubMed PMID: 15670587.
