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排名前五的药物类型	数量

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PI3Kγ x PI3Kδ	1

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1

项与 Biopredict, Inc. 相关的药物

TG-100115

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PI3Kγ x PI3Kδ

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PI3Kγ抑制剂 [+1]

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100 项与 Biopredict, Inc. 相关的临床结果

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0 项与 Biopredict, Inc. 相关的专利（医药）

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9

项与 Biopredict, Inc. 相关的文献（医药）

2023-01-01·Chemical senses

Umami taste perception and preferences of the domestic cat (Felis catus), an obligate carnivore.

Article

作者: Klebansky, Boris ; Waller, Daniel ; Hernangomez de Alvaro, Carlos ; Gibbs, Matthew ; Dunlop, Nicola ; Winnig, Marcel ; McGrane, Scott J

The domestic cat (Felis catus) is an obligate carnivore, and as such has a meat-based diet. Several studies on the taste perception of cats have been reported, indicating that their sense of taste has evolved based on their carnivorous diet. Here, we propose that umami (mediated by Tas1r1-Tas1r3) is the main appetitive taste modality for the domestic cat by characterizing the umami taste of a range of nucleotides, amino acids, and their mixtures for cats obtained using complementary methods. We show for the first time that cats express Tas1r1 in taste papillae. The cat umami receptor responds to a range of nucleotides as agonists, with the purine nucleotides having the highest activity. Their umami receptor does not respond to any amino acids alone; however, 11 l-amino acids with a range of chemical characteristics act as enhancers in combination with a nucleotide. l-Glutamic acid and l-Aspartic acid are not active as either agonists or enhancers of the cat umami receptor due to changes in key binding residues at positions 170 and 302. Overall, cats have an appetitive behavioral response for nucleotides, l-amino acids, and their mixtures. We postulate that the renowned palatability of tuna for cats may be due, at least in part, to its specific combination of high levels of inosine monophosphate and free l-Histidine that produces a strong synergistic umami taste enhancement. These results demonstrate the critical role that the umami receptor plays in enabling cats to detect key taste compounds present in meat.

2010-03-09·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Molecular mechanism of the sweet taste enhancers

1区 · 综合性期刊

Article

作者: Fine, Richard M. ; Liu, Haitian ; Zhang, Feng ; Zoller, Mark ; Li, Xiaodong ; Xu, Hong ; Tachdjian, Catherine ; Klebansky, Boris ; Servant, Guy

Positive allosteric modulators of the human sweet taste receptor have been developed as a new way of reducing dietary sugar intake. Besides their potential health benefit, the sweet taste enhancers are also valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, we reveal how these sweet enhancers work at the molecular level. Our data argue that the sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.

2008-03-01·Journal of Medicinal Chemistry1区 · 医学

Development of Prodrug 4-Chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl Benzoate (TG100801): A Topically Administered Therapeutic Candidate in Clinical Trials for the Treatment of Age-Related Macular Degeneration

1区 · 医学

Article

作者: Soll, Richard ; Umeda, Naoyasu ; Klebansky, Boris ; Kachi, Shu ; Hu, Steven ; Lohse, Dan ; Chow, Chun P. ; McPherson, Andrew ; Yee, Shiyin ; Gritzen, Colleen ; Yokoi, Katsutoshi ; Doukas, John ; Hood, John D. ; Renick, Joel ; Cao, Jianguo ; Kang, Xinshan ; Noronha, Glenn ; Fine, Richard ; Akiyama, Hideo ; Kousba, Ahmed ; Campochiaro, Peter ; Pathak, Ved P. ; Zhu, Hong ; Martin, Michael ; Mak, Chi Ching ; Dellamary, Luis ; Zeng, Binqi ; Palanki, Moorthy S. S.

Age-related macular degeneration (AMD) is one of the leading causes of loss of vision in the industrialized world. Attenuating the VEGF signal in the eye to treat AMD has been validated clinically. A large body of evidence suggests that inhibitors targeting the VEGFr pathway may be effective for the treatment of AMD. Recent studies using Src/YES knockout mice suggest that along with VEGF, Src and YES play a crucial role in vascular leak and might be useful in treating edema associated with AMD. Therefore, we have developed several potent benzotriazine inhibitors designed to target VEGFr2, Src, and YES. One of the most potent compounds is 4-chloro-3-{5-methyl-3-[4-(2-pyrrolidin-1-yl-ethoxy)phenylamino]benzo[1,2,4]triazin-7-yl}phenol ( 5), a dual inhibitor of both VEGFr2 and the Src family (Src and YES) kinases. Several ester analogues of 5 were prepared as prodrugs to improve the concentration of 5 at the back of the eye after topical administration. The thermal stability of these esters was studied, and it was found that benzoyl and substituted benzoyl esters of 5 showed good thermal stability. The hydrolysis rates of these prodrugs were studied to analyze their ability to undergo conversion to 5 in vivo so that appropriate concentrations of 5 are available in the back-of-the-eye tissues. From these studies, we identified 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl benzoate ( 12), a topically administered prodrug delivered as an eye drop that is readily converted to the active compound 5 in the eye. This topically delivered compound exhibited excellent ocular pharmacokinetics and poor systemic circulation and showed good efficacy in the laser induced choroidal neovascularization model. On the basis of its superior profile, compound 12 was advanced. It is currently in a clinical trial as a first in class, VEGFr2 targeting, topically applied compound for the treatment of AMD.

100 项与 Biopredict, Inc. 相关的药物交易

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100 项与 Biopredict, Inc. 相关的转化医学

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