1185019-85-5Relevant academic research and scientific papers
DNA-Model-Based Design and Execution of Some Fused Benzodiazepine Hybrid Payloads for Antibody-Drug Conjugate Modality
Cardarelli, Pina M.,Cheng, Heng,Cho, Patricia,Chowdari, Naidu S.,Deshpande, Madhura,Eastgate, Martin D.,Gangwar, Sanjeev,Guturi, Sivakrishna,Holder, Patrick,Iwuagwu, Christiana,Kanagavel, Kishorekumar,Kanusu, Umamaheswararao,Kotapati, Srikanth,Lakshminarasimhan, Thirumalai,Langley, David R.,Luzung, Michael R.,McDonald, Ivar,Niyogi, Ankita G.,Pan, Chin,Peese, Kevin M.,Rakshit, Souvik,Rao, Chetana,Sarma, Ganapathy,Schmidt, Michael A.,Sidhar, Somprabha,Sivaprakasam, Prasanna,Tan, Yichen,Vaidyanathan, Rajappa,Vite, Gregory,Xie, Chunshan,Zheng, Bin
supporting information, p. 404 - 412 (2021/03/03)
A new series with the tetrahydroisoquinoline-fused benzodiazepine (TBD) ring system combined with the surrogates of (1-methyl-1H-pyrrol-3-yl)benzene ( MPB ) payloads were designed and executed for conjugation with a monoclonal antibody for anticancer therapeutics. DNA models helped in rationally identifying modifications of the MPB binding component and guided structure-activity relationship generation. This hybrid series of payloads exhibited excellent in vitro activity when tested against a panel of various cancer cell lines. One of the payloads was appended with a lysosome-cleavable peptide linker and conjugated with an anti-mesothelin antibody via a site-specific conjugation method mediated by the enzyme bacterial transglutaminase (BTGase). Antibody-drug conjugate (ADC) 50 demonstrated good plasma stability and lysosomal cleavage. A single intravenous dose of ADC 50 (5 or 10 nmol/kg) showed robust efficacy in an N87 gastric cancer xenograft model.
Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481
Boy, Kenneth M.,Guernon, Jason M.,Zuev, Dmitry S.,Xu, Li,Zhang, Yunhui,Shi, Jianliang,Marcin, Lawrence R.,Higgins, Mendi A.,Wu, Yong-Jin,Krishnananthan, Subramaniam,Li, Jianqing,Trehan, Ashok,Smith, Daniel,Toyn, Jeremy H.,Meredith, Jere E.,Burton, Catherine R.,Kimura, S. Roy,Zvyaga, Tatyana,Zhuo, Xiaoliang,Lentz, Kimberley A.,Grace, James E.,Denton, Rex,Morrison, John S.,Mathur, Arvind,Albright, Charles F.,Ahlijanian, Michael K.,Olson, Richard E.,Thompson, Lorin A.,Macor, John E.
, p. 312 - 317 (2019/03/08)
A triazine hit identified from a screen of the BMS compound collection was optimized for potency, in vivo activity, and off-target profile to produce the bicyclic pyrimidine γ-secretase modulator BMS-932481. The compound showed robust reductions of Aβsub
ANTIPROLIFERATIVE COMPOUNDS AND CONJUGATES MADE THEREFROM
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Paragraph 0274; 0276, (2018/05/03)
A compound capable of inhibiting cell proliferation, having a structure according to formula (I) wherein the variables in formula (I) are as defined in the specification. Such compounds are useful as anti-cancer agents, especially in antibody-drug conjugates.
FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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, (2017/05/14)
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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, (2015/08/03)
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
NOVEL SUBSTITUTED TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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, (2012/12/13)
The present invention is concerned with novel substituted triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the mean
NOVEL SUBSTITUTED BICYCLIC TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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, (2011/08/04)
The present invention is concerned with novel substituted bicyclic triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.
NOVEL SUBSTITUTED TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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, (2011/08/04)
The present invention is concerned with novel substituted triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma sec
COMPOUNDS FOR THE REDUCTION OF β-AMYLOID PRODUCTION
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, (2011/02/24)
The present disclosure provides a series of compounds of the formula (I) which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.
NEW COMPOUNDS MODULATING GAMMA-SECRETASE AND THEIR USE IN THE TREATMENT OF ALPHA BETA RELATED PATHOLOGIES, SUCH AS ALZHEIMER'S DISEASE
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, (2010/12/17)
The present invention relates to novel compounds of formulae (I) and (II) and therapeutically acceptable salts thereof, their pharmaceutical compositions processes for making them and their use in therapeutic methods for treatment and/or prevention of var
