Abstract: This invention provides compositions and methods for treatment of mild, moderate and severe stages of SARS-CoV-2 infection, particularly COVID-19 disease caused by wild type and mutant strains of SARS-CoV-2 using 5-amino-1-(4-(4-chlorobenzyl)-1,2,3-triazole-4-carboxamide orotate. Carboxyamidotriazole orotate (CTO) alone or in combination with other therapeutics in standard of clinical care are useful for directing antiviral effects and host-directed antiviral effects against wild type and mutant strains of SARS-CoV-2 throughout the viral life cycle.

Abstract: This invention provides compositions and methods for treatment of mild, moderate and severe stages of SARS-CoV-2 infection, particularly COVID-19 disease caused by wild type and mutant strains of SARS-CoV-2 using 5-amino-1-(4-(4-chlorobenzyl)-1, 2, 3-triazole-4-carboxamide orotate. Carboxyamidotriazole orotate (CTO) alone or in combination with other therapeutics in standard of clinical care are useful for directing antiviral effects and host-directed antiviral effects against wild type and mutant strains of SARS-CoV-2 throughout the viral life cycle.

Abstract: This invention provides methods, pharmacodynamics biomarker signatures for multiple signaling pathways in a cell sample such as anagen hair, in response to carboxyamidotriazole orotate (CTO) from a subject. CTO has demonstrated response in several cancers having different genomic mutations in clinical studies. This invention provides a diagnostic and prognostic assay for monitoring response to CTO ranging from ?100 fold to +25 fold differential expression in several transcriptional signatures associated with tumor inhibition including EGFR, MEK, HDAC, RAS, GFS, WNT, HSP90 or non-voltage dependent calcium signaling, while inducing tumor suppressors signatures such as P53 or EGR1 in the anagen hair assay.

Abstract: This invention provides methods and compositions useful for treating early and late stage metastatic cancer to prevent or treat acquired resistance due to gene amplification or mutation in response to chemotherapeutic and/or targeted drugs. In particular, the methods and compositions include carboxiamidotriazole orotate (CTO) alone or in combination with specific regimens of chemotherapeutic and/or targeted drags designed to overcome the genomic resistance raised to prior therapy.

Abstract: This invention provides methods and compositions useful for treating early and late stage metastatic cancer to prevent or treat acquired resistance due to gene amplification or mutation in response to chemotherapeutic and/or targeted drugs. In particular, the methods and compositions include carboxiamidotriazole orotate (CTO) alone or in combination with specific regimens of chemotherapeutic and/or targeted drugs designed to overcome the genomic resistance raised to prior therapy.

Abstract: This invention provides methods, pharmacodynamics biomarker signatures for multiple signaling pathways in a cell sample such as anagen hair, in response to carboxyamidotriazole orotate (CTO) from a subject. CTO has demonstrated response in several cancers having different genomic mutations in clinical studies. This invention provides a diagnostic and prognostic assay for monitoring response to CTO ranging from ?100 fold to +25 fold differential expression in several transcriptional signatures associated with tumor inhibition including EGFR, MEK, HDAC, RAS, GFS, WNT, HSP90 or non-voltage dependent calcium signaling, while inducing tumor suppressors signatures such as P53 or EGR1 in the anagen hair assay.

Abstract: New polymorphs of 5-amino or substituted amino 1,2,3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes of the preparation of the same are disclosed. The compounds are useful in the control and treatment of diseases including, but not limited to solid cancers, macular degeneration, retinopathy, chronic myeloid leukemia, AIDS and diseases which rely on aberrant signal transduction. The improved processes to prepare the orotate formulations use stable, efficient and safer starting azide intermediate materials in the synthesis of new polymorphs of carboxyamidotriazole.

Abstract: This invention relates to enhancing sensitivity of cytotoxic drugs by targeting their interfering mechanisms induced in the tumor microenvironment which lead to drug resistance, using combinatorial therapy with carboxyamidotriazole orotate. Specific doses of cytotoxic drugs are titrated with carboxyamidotriazole orotate to improve the sensitivity and anticancer activity of cytotoxic drugs.

Abstract: This invention provides methods and compositions useful for treating early and late stage metastatic cancer to prevent or treat acquired resistance due to gene amplification or mutation in response to chemotherapeutic and/or targeted drugs. In particular, the methods and compositions include carboxiamidotriazole orotate (CTO) alone or in combination with specific regimens of chemotherapeutic and/or targeted drugs designed to overcome the genomic resistance raised to prior therapy.

Abstract: This invention is in the field of anthracycline family of drugs. More particularly, it concerns converting daunorubicin hydrochloride to an orotate salt and providing methods of improving the tolerability of daunorubicin in animals by reducing the adverse effects and toxicity in noncancerous tissues. Daunorubicin orotate provides a safer treatment for specific types of leukemias and neuroblastomas in adults and in pediatric patients.

Abstract: New polymorphs of 5-amino or substituted amino 1,2,3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes of the preparation of the same are disclosed. The compounds are useful in the control and treatment of diseases including, but not limited to solid cancers, macular degeneration, retinopathy, chronic myeloid leukemia, AIDS and diseases which rely on aberrant signal transduction. The improved processes to prepare the orotate formulations use stable, efficient and safer starting azide intermediate materials in the synthesis of new polymorphs of carboxyamidotriazole.

Abstract: Method and composition of Carboxyamidotriazole orotate for treating age-related macular degeneration and other angiogenesis-dependent diseases.

Abstract: This invention is related to orotic acid compounds of taxane cytotoxic agents and in particular to the conversion of the taxanes to their orotate esters. More particularly the pharmaceutical compositions of paclitaxel orotate and docetaxel orotate provide a strategy to minimize body weight loss during primary chemotherapy and improve patient outcomes and quality of life.

Abstract: New polymorphs of 5-amino or substituted amino 1,2,3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes of the preparation of the same are disclosed. The compounds are useful in the control and treatment of diseases including, but not limited to solid cancers, macular degeneration, retinopathy, chronic myeloid leukemia, AIDS and diseases which rely on aberrant signal transduction. The improved processes to prepare the orotate formulations use stable, efficient and safer starting azide intermediate materials in the synthesis of new polymorphs of carboxyamidotriazole.

Abstract: This invention relates to enhancing sensitivity of cytotoxic drugs by targeting their interfering mechanisms induced in the tumor microenvironment which lead to drug resistance, using combinatorial therapy with carboxyamidotriazole orotate. Specific doses of cytotoxic drugs are titrated with carboxyamidotriazole orotate to improve the sensitivity and anticancer activity of cytotoxic drugs.

Abstract: This invention is in the field of anthracycline family of drugs. More particularly, it concerns converting daunorubicin hydrochloride to an orotate salt and providing methods of improving the tolerability of daunorubicin in animals by reducing the adverse effects and toxicity in noncancerous tissues. Daunorubicin orotate provides a safer treatment for specific types of leukemias and neuroblastomas in adults and in pediatric patients.

Abstract: This invention is related to orotic acid compounds of taxane cytotoxic agents and in particular to the conversion of the taxanes to their orotate esters. More particularly the pharmaceutical compositions of paclitaxel orotate and docetaxel orotate provide a strategy to minimize body weight loss during primary chemotherapy and improve patient outcomes and quality of life.

Abstract: This invention is in the field of chemical restructuring of pharmaceutical agents known to cause tissue toxicity as a side effect, by producing their orotate salts. More particularly, it concerns orotate salts of the anthracyclines, doxorubicin and daunorubicin, that are found to reduce levels of the pharmaceutical agent in noncancerous tissues. The orotate salts are equally efficacious in inhibiting the SCCAKI-1 kidney tumor in animals and the reduction in the heart tissue of doxorubicin compared with doxorubicin HCl suggests a reduction in toxicity induced by free radical generation by the anthracyclines.

Abstract: The present invention relates generally to the method of increasing the oral bioavailability, reducing chemotherapy induced toxicity and side effects, and improving the effectiveness of pharmaceutical agents that are poorly absorbed from the gastrointestinal tract. Specifically, the invention relates to poorly absorbed pharmaceutical drugs and converting them to orotate salts. The orotate salts of the drugs can be dosed at lower doses to provide the efficacy benefits of a higher dose, while reducing the drugs' toxic effects at lower doses. Additionally, the orotate salts of pharmaceutical agents have better clearance and reduce the potential for drug-induced hepatic toxicity. Therefore, an especially useful formulation of the orotate salt of the pharmaceutical agent can provide rapid and consistent action using a lower dose while reducing drug interactions and side-effects.

Abstract: New polymorphs of 5-amino or substituted amino 1,2,3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes of the preparation of the same are disclosed. The compounds are useful in the control and treatment of diseases including, but not limited to solid cancers, macular degeneration, retinopathy, chronic myeloid leukemia, AIDS and diseases which rely on aberrant signal transduction. The improved processes to prepare the orotate formulations use stable, efficient and safer starting azide intermediate materials in the synthesis of new polymorphs of carboxyamidotriazole.