Drug rescue by redesign of ADMET/PK properties
OwnerHarold E. Selick, Kenneth R. Korzekwa +1inventors
InventorsHarold E. Selick, Kenneth R. Korzekwa, Katrin Mackarehtschian
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Abstract
Otherwise efficacious drugs having an ADMET/PK (absorption, distribution, metabolism, elimination, toxicity, i.e., pharmacokinetic) problem are redesigned or “rescued” by applying computational techniques that identify related chemical structures that preserve the initial drug's effectiveness but improve its ADMET/PK properties. The otherwise efficacious drug may be subjected to a suite of computational tools that identify sites responsible for problematic ADMET/PK properties and/or identify related compounds that have improved ADMET/PK properties.
Claims92
A method of redesigning a therapeutic chemical compound to improve at least one of its ADMET/PK properties, the method comprising:
- (a) identifying a therapeutic chemical compound that is a drug or withdrawn drug;
- (b) analyzing the structure of the therapeutic chemical compound with a model that predicts one or more ADMET/PK properties of chemical compounds based upon their chemical structures;
- (c) from an analysis of the therapeutic chemical compound with the model, identifying one or more structural features of the therapeutic chemical compound that cause the therapeutic chemical compound to possess an ADMET/PK property that can be improved;
- and
- (d) specifying a modification for the one or more structural features identified in (c) to produce a modified chemical compound exhibiting an improvement in the one or more ADMET/PK properties over the therapeutic chemical compound, while substantially preserving a therapeutic effectiveness exhibited by the therapeutic chemical compound.
A computer-program product comprising a computer-readable medium and program instructions provided via the computer-readable medium, the program instructions comprising instructions for redesigning a therapentic chemical compound to improve at least one of its ADMET/PK properties, the instructions specifying:
- (a) identifying a therapeutic chemical compound that is a drug or withdrawn drug;
- (b) analyzing the structure of the therapeutic chemical compound witha model that predicts one or more ADMET/PK properties of chemical compounds based upon their chemical structures;
- (c) from an analysis of the therapeutic chemeical compound with the model, identifying one or more structural features of the therapeutic chemical compound that cause the therapeutic chemical compound to possess an ADMET/PK property that can be improved;
- and
- (d) specifying a modification for the one or more structural features identified in (c) to produce a modified chemical compound exhibiting an improvement in the one or more ADMET/PK properties over the therapeutic chemical compound, while substantially preserving a therapeutic effectiveness exhibited by the therapeutic chemical compound.
An apparatus for analyzing therapeutic chemical compounds in order ot redesign the therapeutic chemical compounds, the apparatue comprising:
- (a) an interface for receiving information, including the identity of chemical compounds, form at least one external source;
- (b) a memory device for storing, at least temporarily, (i) chemical structural information of a therapeutic chemical compound that is a drug cndidate, drug or withdrawn drug and (ii) instructions for analyzing one or more ADMET/PK propertics of the therapeutic chemical compound;
- and
- (c) on or more processors designed or configured to
- (i) identify one or more structural features of the therapeutic chemical compound that cause the therapeutic chemical compound to possess an ADMET/PK property that can be improved, and
- (ii) specify a modification for the one or more structural features to produce a modified chemical compound exhibiting an improvement in the one or more ADMET/PK properties over the therapeutic chemical compound, while substantially preserving a therapeutic effectiveness exhibited by the therapeutic chemical compound.
A method of analyzing a therapeutic chemical compound to redesign the therapeutic chemical compound, the method comprising:
- (a) identifying a therapeutic chemical compound that is a drug candidate, drug or withdrawn drug;
- (b) utilizing a software application or integrated suite of software applications to analyze the therapeutic chemical compound, wherein the software application or integrated suite of software applications can analyze at least two of the following properties of the therapeutic chemical compound:
- absorption, metabolism, distribution and toxicity;
- and
- (c) specifying a modification to the therapeutic compound in order to modify at least one of the following properties of the therapeutic compound:
- absorption, metabolism, distribution, excretion, and toxicity.
A computer-program product comprising a computer-readable medium and program instructions provided via the computer-readable medium, the program instructions comprising instructions for analyzing a therapeutic compound to redesign the therapeutic chemical compound, the computer-program product comprising instructions for:
- (a) identifying a therapeutic chemical compound that is a drug candidate, drug or withdrawn drug;
- (b) utilizing a software application or integrated suite of software applications to analyze the therapeutic chemical compound, wherein the software application or integrated suite of software applications can analyze at least two of the following properties of the therapeutic chemical compound:
- absorption, metabolism, distribution, and toxicity;
- and
- (c) specifying a modification to the therapeutic compound in order to modify at least one of the following properties of the therapeutic compound:
- absorption, metabolism, distribution, excretion, and toxicity.
An apparatus for analyzing therapeutic chemical compounds to redesign the therapeutic chemical compounds, the apparatus comprising:
- (a) an interface for receiving information, including the identity of chemical compounds, from at least one external source;
- (b) a memory device for storing, at least temporarily, (i) chemical structural information of a therapeutic chemical compound that is a drug candidate, drug or withdrawn drug and (ii) instructions for analyzing at least two of the following properties of the therapeutic chemical compound:
- absorption, metabolism, distribution and toxicity;
- and
- (c) one or more processors designed or configured to
- (i) analyze the therapeutic chemical compound stored in memory by evaluating at least two of the following properties of the therapeutic chemical compound:
- absorption, metabolism, distribution and toxicity, and
- (ii) specify a modification to the therapeutic compound in order to modify at least one of the following properties of the therapeutic compound:
- absorption, metabolism, distribution and toxicity.
Dependencies are inferred from the claim text.