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Methods and systems for the identification of components of mammalian biochemical networks as targets for therapeutic agents

Systems and methods are presented for cell simulation and cell state prediction. For example, a cellular biochemical network intrinsic to a phenotype of a cell can be simulated by specifying its components and their interrelationships. The various interrelationships can be represented with one or more mathematical equations which can be solved to simulate a first state of the cell. The simulated network can then be perturbed, and the equations representing the perturbed network can be solved to simulate a second state of the cell which can then be compared to the first state, identifying the effect of such perturbation on the network, and thereby identifying one or more components as targets. Alternatively, components of a cell can be identified as targets for interaction with therapeutic agents based upon an analytical approach, in which a stable phenotype of a cell is specified and correlated to the state of the cell and the role of that cellular state to its operation. A cellular biochemical network believed intrinsic to that phenotype can then be specified, mathematically represented, and perturbed, and the equations representing the perturbed network solved, thereby identifying one or more components as targets.
Owner:CORNELL RES FOUNDATION INC +1

Methods and systems for the identification of components of mammalian biochemical networks as targets for therapeutic agents

Systems and methods for modeling the interactions of the several genes, proteins and other components of a cell, employing mathematical techniques to represent the interrelationships between the cell components and the manipulation of the dynamics of the cell to determine which components of a cell may be targets for interaction with therapeutic agents. A first such method is based on a cell simulation approach in which a cellular biochemical network intrinsic to a phenotype of the cell is simulated by specifying its components and their interrelationships. The various interrelationships are represented with one or more mathematical equations which are solved to simulate a first state of the cell. The simulated network is then perturbed by deleting one or more components, changing the concentration of one or more components, or modifying one or more mathematical equations representing the interrelationships between one or more of the components. The equations representing the perturbed network are solved to simulate a second state of the cell which is compared to the first state to identify the effect of the perturbation on the state of the network, thereby identifying one or more components as targets. A second method for identifying components of a cell as targets for interaction with therapeutic agents is based upon an analytical approach, in which a stable phenotype of a cell is specified and correlated to the state of the cell and the role of that cellular state to its operation. A cellular biochemical network believed to be intrinsic to that phenotype is then specified by identifying its components and their interrelationships and representing those interrelationships in one or more mathematical equations. The network is then perturbed and the equations representing the perturbed network are solved to determine whether the perturbation is likely to cause the transition of the cell from one phenotype to another, thereby identifying one or more components as targets.
Owner:HILL COLIN +2

Preparation method of LCZ696 intermediate

The invention discloses a preparation method of LCZ696 intermediate and relates to the technical field of preparation of an aromatic nucleus compound containing 2 benzene rings and 1 chiral center. The preparation method includes the steps of S1, allowing benzyl magnesium bromide to react with methyl oxalyl chloride to obtain a compound as shown in formula I; S2, allowing the compound as shown in formula I to have a bromination reaction with a bromination reagent to generate a compound as shown in formula II; S3, coupling the compound as shown in formula II with phenylboronic acid to obtain a compound as shown in formula III; S4, performing reductive ammoniation on the compound as shown in formula III to obtain a compound as shown in formula IV; S5, applying Boc to the compound as shown in formula IV to obtain a compound as shown in formula V; S6, performing ester group reduction on the compound as shown in formula V to obtain a compound as shown in formula VI. The preparation method has the advantages that overall raw material consumption is lowered, and product productivity and market competiveness are increased; by the overall process optimization, the reaction of each step can be performed and controlled easily, the use of heavy metal catalysts is reduced and avoided, and accordingly the quality index of the final product is increased, and an economic and environment-friendly process route is developed.
Owner:CANGZHOU SENARY CHEM SCI TEC
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