Abstract: RAS modulating compounds and methods of using the same are provided. The compounds find use in modulating the activity of a target RAS in a sample. The target RAS can be a mutant RAS that is implicated in a disease of interest. In some cases, the subject compounds can inhibit the growth of cancer cells whose progression is driven by kRAS or a mutated kRAS. Methods of treating a subject for a RAS driven disease including administering a therapeutically effective amount of the subject compound are provided. Also provided are pharmaceutical compositions and kits which include the subject compounds.

Abstract: Methods of treating a subject for a liver condition, e.g., NAFLD, NASH, and/or DILI, are provided. Aspects of the methods include administering to the subject an effective amount of a UPase inhibitor, optionally in combination with a uridine active agent (e.g., uridine (UR), a UR pro-drug or a UR mimetic), such as supplemental uridine, to treat the subject for the liver condition. Also provided are compositions for use in practicing the subject methods.

Abstract: Pyrazolopyrimidine RAS modulating compounds and methods of using the same are provided. The pyrazolopyrimidine compounds find use in modulating the activity of a target RAS in a sample. The target RAS can be a mutant RAS that is implicated in a disease of interest. In some cases, the subject compounds can inhibit the growth of cancer cells whose progression is driven by kRAS or a mutated kRAS. Methods of treating a subject for a RAS driven disease including administering a therapeutically effective amount of the subject compound are provided. Also provided are pharmaceutical compositions and kits which include the subject compounds.

Abstract: Non-mammalian, transgenic animals, e.g., flies, that include a RAS transgene, are provided. Also provided are methods of using the subject transgenic non-mammalian animals to identify compounds having activity with respect to cellular proliferative, such as neoplastic, diseases.

Abstract: Methods are provided for using doxorubicin active agents in which reduced host toxicity is observed. Aspects of the methods including administering to a subject an effective amount of a doxorubicin active agent in conjunction with a doxorubicin toxicity-reducing adjuvant, e.g., a nitrone compound, or a nitrone compound in combination with a bisdioxopiperazine compound. Also provided are compositions for use in practicing the subject methods. The methods and compositions find use in a variety of different applications, including in the treatment of a variety of different disease conditions.

Abstract: Methods are provided for using methotrexate (MTX) active agents in which reduced host toxicity is observed. Aspects of the methods include administering to a subject an effective amount of an MTX active agent in conjunction with a MTX toxicity-reducing adjuvant, such as a 2,2?-anhydropyrimidine, a derivative thereof or a uridine phosphorylase inhibitor. Also provided are compositions and kits that find use in practicing embodiments of the invention. The methods and compositions find use in a variety of applications, including the treatment of a variety of different disease conditions.

Abstract: A high throughput toxicology screening method is provided. In the subject method, at least 10 different compound compositions are tested simultaneously. Each compound composition is tested by contacting it with a plurality, e.g. from about 10 to 1000, of non-mammalian multi-cellular organisms and determining the effect of the compound composition on the organisms. The multi-cellular organisms employed in the subject methods are small, have differentiated tissues and organs and have a rapid generation time. The subject high throughput screening methods find use in a variety of applications, and are particularly suited for use in the toxicology screening of libraries of compounds, such as libraries of combinatorially produced compounds.

Abstract: Methods for homologously recombining an exogenous nucleic acid into a target cell genome of a target cell are provided. In the subject methods, a targeting vector that includes a linearizing endonuclease site, e.g., a recombinase recognition site, and a homologous recombination integrating element, is contacted with the target cell(s) such that the target cell(s) take up the targeting vector. The targeting vector is originally a circular targeting vector that is linearized by a linearizing endonuclease, e.g., a recombinase, either prior to administration (e.g., in vitro treatment with an endonuclease) or upon entry into the multicellular organism by endonucleases in the extracellular or intracellular fluids that can be introduced to or already present in the muticellular organism. The integrating element homologously recombines into the target cell genome from the linearized targeting vector. Also provided are targeting vectors, systems and kits for use in practicing the subject methods.

Abstract: Methods for homologously recombining an exogenous nucleic acid into a target cell genome of a multicellular organism, e.g., an animal, are provided. In the subject methods, a targeting vector that includes a linearizing endonuclease site, e.g., a recombinase recognition site, and a homologous recombination integrating element, is contacted with the multicellular organism, e.g., via systemic or local administration, such that the target cell(s) of the multicellular organism takes up the targeting vector. The targeting vector is one that has been linearized by a linearizing endonuclease, e.g., a recombinase, at some point prior to the homologous recombination event, e.g., prior to or after contact with the multicellular organism. Following uptake by the target cell(s), the integrating element then homologously recombines into the target cell genome from the linearized targeting vector. Also provided are targeting vectors, systems and kits for use in practicing the subject methods.

Abstract: Novel P element derived vectors and methods for their use to insert an exogenous nucleic acid into the genome of a target cell are provided. The subject vectors have a pair of P element transposase recognized insertion sites, e.g. 31 base pair inverted repeats, flanking at least two transcriptionally active genes. In practicing the subject methods, a vector of the subject invention is introduced into the target cell under conditions sufficient for transposition to occur. The subject methods find use in a variety of applications in which the insertion of an exogenous nucleic acid into the genome of a target cell is desired, e.g. include research, synthesis and therapeutic applications.

Abstract: A high throughput toxicology screening method is provided. In the subject method, at least 10 different compound compositions are tested simultaneously. Each compound composition is tested by contacting it with a plurality, e.g. from about 10 to 1000, of non-mammalian multi-cellular organisms and determining the effect of the compound composition on the organisms. The multi-cellular organisms employed in the subject methods are small, have differentiated tissues and organs and have a rapid generation time. The subject high throughput screening methods find use in a variety of applications, and are particularly suited for use in the toxicology screening of libraries of compounds, such as libraries of combinatorially produced compounds.

Abstract: Non-mammalian, transgenic animals, e.g. flies, that exhibit neoplastic phenotypes, i.e. spontaneously produce metastatic tumors, are provided. Also provided are methods of using the subject transgenic non-mammalian animals to identify compounds having activity with respect to cellular proliferative, and particularly neoplastic, diseases. Finally, kits for screening compounds for anti-neoplastic activity are provided.

Abstract: Novel P element derived vectors and methods for their use to insert an exogenous nucleic acid into the genome of a target cell are provided. The subject vectors have a pair of P element transposase recognized insertion sites, e.g. 31 base pair inverted repeats, flanking at least two transcriptionally active genes. In practicing the subject methods, a vector of the subject invention is introduced into the target cell under conditions sufficient for transposition to occur. The subject methods find use in a variety of applications in which the insertion of an exogenous nucleic acid into the genome of a target cell is desired, e.g. include research, synthesis and therapeutic applications.

Abstract: Methods are provided for using methotrexate (MTX) active agents in which reduced host toxicity is observed. Aspects of the methods include administering to a subject an effective amount of an MTX active agent in conjunction with a MTX toxicity-reducing adjuvant, such as a 2,2?-anhydropyrimidine, a derivative thereof or a uridine phosphorylase inhibitor. Also provided are compositions and kits that find use in practicing embodiments of the invention. The methods and compositions find use in a variety of applications, including the treatment of a variety of different disease conditions.