Identification of genotype-selective anti-tumor agents
First Claim
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1. A method of identifying an agent that is selectively toxic to human tumorigenic cells, comprising:
- (a) contacting test cells, which are engineered human tumorigenic cells, with a candidate agent;
(b) determining viability of test cells contacted in (a) with the candidate agent; and
(c) comparing the viability of test cells determined in (b) with an appropriate control, wherein if the viability of the test cells is less than that of the control cells, then an agent that is selectively toxic to engineered human tumorigenic cells is identified.
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Abstract
The present invention relate to methods of identifying a genotype-selective agent. In certain embodiments, the invention relates to agents that are selectively toxic to engineered human tumorigenic cells.
55 Citations
66 Claims
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1. A method of identifying an agent that is selectively toxic to human tumorigenic cells, comprising:
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(a) contacting test cells, which are engineered human tumorigenic cells, with a candidate agent;
(b) determining viability of test cells contacted in (a) with the candidate agent; and
(c) comparing the viability of test cells determined in (b) with an appropriate control, wherein if the viability of the test cells is less than that of the control cells, then an agent that is selectively toxic to engineered human tumorigenic cells is identified. - View Dependent Claims (3, 4, 5, 6, 14, 15, 16, 17, 18, 59, 60, 61, 65)
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2. A method of identifying an agent that is toxic to human tumorigenic cells, comprising:
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(a) contacting test cells, which are engineered human tumorigenic cells, with a candidate agent;
(b) determining viability of test cells contacted in (a) with the candidate agent; and
(c) comparing the viability of test cells determined in (b) with an appropriate control, wherein if the viability of the test cells is less than that of the control cells, then an agent that is toxic to engineered human tumorigenic cells is identified. - View Dependent Claims (19, 20, 21, 22, 23, 62, 63, 64, 66)
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7. A method of inducing death in tumor cells, comprising contacting the cells with a compound selected from the group consisting of:
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(a) a compound having the following formula;
(b) a compound having the following formula;
(c) a compound that is an analog of (a) and is selectively toxic to tumor cells.
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8. A method of inducing death in cells in which the RAS pathway is activated, comprising contacting the cells with a compound selected from the group consisting of:
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(a) a compound having the following formula;
(b) a compound having the following formula;
(c) a compound that is an analog of (a) and is selectively toxic to cells in which the RAS pathway is activated.
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9. A method of inducing death in human cells expressing SV40 small T oncoprotein and oncogenic HRAS, comprising contacting the human cells with a compound selected from the group consisting of:
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(a) a compound having the following formula;
(b) a compound having the following formula;
(c) a compound that is an analog of (a) and is selectively toxic to human cells expressing SV40 small T oncoprotein and oncogenic HRAS.
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- 10. A compound having the following formula:
- 12. A compound having the following formula:
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24. A method of identifying a cellular component involved in tumorigenesis, comprising:
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(a) contacting a cell with erastin; and
(b) identifying a cellular component that interacts with erastin, wherein the cellular component that is identified is a cellular component involved in tumorigenesis. - View Dependent Claims (25, 26, 27)
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28. A method of identifying a cellular component that interacts with erastin, comprising:
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(a) contacting a cell with erastin; and
(b) identifying a cellular component that interacts with erastin, wherein the cellular component that is identified is a cellular component that interacts with erastin. - View Dependent Claims (29, 30, 31)
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32. A method of identifying a cellular component involved in tumorigenesis, comprising:
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(a) contacting a cell with an inhibitor of erastin and contacting a cell with erastin; and
(b) identifying a cellular component that interacts with the inhibitor in (a), wherein the cellular component that is identified is a cellular component involved in tumorigenesis. - View Dependent Claims (33, 34, 35)
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36. A method of identifying a cellular component that interacts with erastin, comprising:
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(a) contacting a cell with an inhibitor of erastin and contacting a cell with erastin; and
(b) identifying a cellular component that interacts with the inhibitor in (a), wherein the cellular component that is identified is a cellular component that interacts with erastin. - View Dependent Claims (37, 38, 39)
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40. A method of identifying an agent that interacts with a cellular component involved in tumorigenesis, comprising:
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(a) contacting a cell with erastin;
(b) identifying a cellular component that interacts with erastin;
(c) contacting a cell with a candidate agent; and
(d) identifying an agent that interacts with the cellular component in (b), wherein the agent that interacts with the cellular component is identified as an agent that interacts with a cellular component involved in tumorigenesis. - View Dependent Claims (41, 42, 43, 44, 53, 54, 55)
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45. A method of identifying an agent that interacts with a cellular component that interacts with erastin, comprising:
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(a) contacting a cell with erastin;
(b) identifying a cellular component that interacts with erastin;
(c) contacting a cell with a candidate agent; and
(d) identifying an agent that interacts with the cellular component in (b), wherein the agent that interacts with the cellular component is identified as an agent that interacts with a cellular component that interacts with erastin. - View Dependent Claims (46, 47, 48, 49, 56, 57, 58)
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50. A method of identifying an agent that induces death in tumor cells by a non-apoptotic mechanism, comprising:
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(a) contacting test cells with a candidate agent that induces death in tumor cells;
(b) assessing whether the agent in (a) induces apoptosis in test cells; and
(c) comparing induction of apoptosis in cells in (b) with an appropriate control, wherein if apoptosis is induced in control cells but not in test cells, then an agent that induces death in tumor cells by a non-apoptotic mechanism is identified. - View Dependent Claims (51, 52)
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Specification