A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986104 in Healthy Male Subjects

The primary objective in this study is to assess if single doses of BMS-986104 that are safe, tolerable, and result in sufficient lymphopenia (50% to 70% reduction in absolute lymphocyte count) can be achieved without bradycardia or other adverse events in healthy male subjects.

开始日期2014-08-01

申办/合作机构

Bristol Myers Squibb Co.

100 项与 BMS-986104 相关的临床结果

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100 项与 BMS-986104 相关的转化医学

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100 项与 BMS-986104 相关的专利（医药）

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项与 BMS-986104 相关的文献（医药）

2025-01-22·Journal of the American Chemical Society

Chiral Aldehyde/Palladium Catalysis Enables Asymmetric Branched-Selective Ring-Opening Functionalization of Methylenecyclopropanes with Amino Acid Esters

Article

作者: He, Hui ; Guan, Hong-Lin ; Zhu, Fang ; Wen, Wei ; Guo, Qi-Xiang ; Ni, Shao-Fei ; Wu, Zhu-Lian ; Cai, Tian

Achieving catalytic asymmetric functionalization of methylenecyclopropanes (MCPs) by selective C-C bond cleavage is a notable challenge due to the intricate reaction partners involved. In this work, we report that chiral aldehyde/palladium combined catalysis enables the asymmetric functionalization of MCPs with NH₂-unprotected amino acid esters. This reaction proceeds through a regiospecific branched ring-opening mechanism, resulting in optically active α,α-disubstituted α-amino acid esters bearing nonconjugated terminal alkene units. Mechanism studies indicate that the ring-opening pathways are irreversible and the ultimate regioselectivity is governed by palladium catalysis. The products can be utilized in the construction of chiral dihydropyrazoles, α-methyl aspartic acid derivatives, and analogues of VPC01091 and BMS-986104.

2018-08-01·Journal of Pharmaceutical and Biomedical Analysis3区 · 医学

Overcoming the stability, solubility and extraction challenges in reversed-phase UHPLC–MS/MS bioanalysis of a phosphate drug and its prodrug in blood lysate

3区 · 医学

Article

作者: Yuan, Long ; Basdeo, Shenita ; Ji, Qin C

BMS-986104 is a S1P₁R modulator drug candidate under development and has been evaluated in Phase I clinical trials. BMS-986104 functions as a prodrug and undergoes enzymatic transformations in vivo to form the pharmacologically active phosphate drug, BMS-986104-P. Here, we report approaches to overcome the stability, solubility and extraction challenges in developing a sensitive, accurate and rugged LC-MS/MS method for the simultaneous quantification of the phosphate drug and its prodrug in blood lysate. An effective stabilization strategy using a cocktail of phosphatase and kinase inhibitors was developed to ensure the stability of both analytes during sample collection, storage, and processing. A combination of surfactant (CHAPS) and weak base (Tris) was found to be able to effectively improve the solubilization of the phosphate drug. The blood lysate samples were extracted by protein precipitation followed by solid-phase extraction using an Oasis HLB 96-well SPE plate. The method achieved acceptable matrix effect and recovery for the two analytes that have very different chemical properties. Stable-isotope labeled D6-BMS-986104 and D13-BMS-986104-P were utilized as the internal standards. Chromatographic separation was achieved using isocratic conditions on an Acquity UPLC BEH C18 analytical column. The two analytes and their internal standards were detected by positive ion electrospray tandem mass spectrometry. The calibration curves, which ranged from 2.00 to 2000 ng/mL for BMS-986104 and 4.00 to 4000 ng/mL for BMS-986104-P, were fitted to a 1/x2 weighted linear regression model. The intra-assay precision was within ±5.0% CV, inter-assay precision was within ±4.9% CV, and the assay accuracy was within ±5.8% of the nominal values for both analytes in rat blood lysate. The method was validated and successfully applied to support multiple pre-clinical toxicity studies.

2016-12-22·Journal of Medicinal Chemistry1区 · 医学

Asymmetric Hydroboration Approach to the Scalable Synthesis of ((1R,3S)-1-Amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986104) as a Potent S1P₁ Receptor Modulator

1区 · 医学

Article

作者: Dyckman, Alaric J. ; Marino, Anthony M. ; Gilmore, John L. ; Mathur, Arvind ; Gupta, Anuradha ; Li, Peng ; Cornelius, Georgia ; Carter, Percy H. ; Xie, Jenny H. ; Lehman-McKeeman, Lois D. ; Balimane, Praveen ; Borowski, Virna ; Yang, Zheng ; Feng, Jianlin ; Yang, Michael G. ; Li, Yu-Wen ; Xiao, Hai-Yun ; Cvijic, Mary Ellen ; Marcoux, David ; Dhar, T. G. Murali ; Wu, Dauh-Rurng ; Heimrich, Elizabeth ; Xiao, Zili ; Pragalathan, Bala ; Barrish, Joel C. ; McIntyre, Kim W. ; Fernandes, Alda ; Shen, Ding Ren ; Warrack, Bethanne M. ; Taylor, Tracy L. ; Salter-Cid, Luisa

We describe a highly efficient route for the synthesis of 4a (BMS-986104). A key step in the synthesis is the asymmetric hydroboration of trisubstituted alkene 6. Particularly given the known difficulties involved in this type of transformation (6 → 7), the current methodology provides an efficient approach to prepare this class of compounds. In addition, we disclose the efficacy of 4a in a mouse EAE model, which is comparable to 4c (FTY720). Mechanistically, 4a exhibited excellent remyelinating effects on lysophosphatidylcholine (LPC) induced demyelination in a three-dimensional brain cell culture assay.

100 项与 BMS-986104 相关的药物交易

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