A combination therapy involving different therapeutic molecules can enhance and improve the therapeutic potentials. An effective therapeutic strategy conjugates silica (SiO.sub.2) nanoparticles with, e.g., 3-glycidyloxypropyl, trimethoxysilane and azoles, e.g., 1,2,4-triazole (Tri), 3-aminotriazole (ATri), 5-aminetetrazole (Atet), imidazole (Imi). These exemplary materials—classified as SiO.sub.2-3GPS-Tri (Conj. 1), SiO.sub.2-3GPS-Atri (Conj. 2), SiO.sub.2-3GPS-Atet (Conj. 3), SiO.sub.2-3GPS-Btri (Conj. 4), and SiO.sub.2-3GPS-Imi (Conj. 5)—can amplify targeting of therapeutics for human colorectal carcinoma cells (HCT-116), enhancing anti-cancer effects.

The invention provides bifunctional compounds of formula (I) or a pharmaceutically acceptable salt thereof. Formula (I). The compounds cause the degradation of SMARCA2 via the targeted ubiquination of SMARCA2 protein and subsequent proteasomal degradation and are thus useful for the treatment of cancer. The targeting ligand is of formula (TL).

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The invention provides bifunctional compounds of formula (I) or a pharmaceutically acceptable salt thereof. Formula (I). The compounds cause the degradation of SMARCA2 via the targeted ubiquination of SMARCA2 protein and subsequent proteasomal degradation and are thus useful for the treatment of cancer. The targeting ligand is of formula (TL).

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Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation/disruption compounds including a HPK1 ligand, a degradation/disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation/disruption compounds including a HPK1 ligand, a degradation/disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

Disclosed are bispecific compounds (degraders) that target α-synuclein protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat neurodegenerative diseases.

Disclosed are bispecific compounds (degraders) that target ITK or a zinc finger (ZnF) protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by ITK or ZnF protein activity.

The present invention provides for a method of treating a disease such as cancer, comprising the step of administering to a patient a therapeutically effective amount of a perillyl alcohol derivative such as a perillyl alcohol ester, or an isoperillyl alcohol derivative such as an isoperillyl alcohol ester. The derivative may be a perillyl alcohol or an isoperillyl alcohol conjugated with a therapeutic agent such as valproic acid. The route of administration may vary, including inhalation, intranasal, oral, transdermal, intravenous, subcutaneous or intramuscular injection.

The present invention provides for a method of treating a disease such as cancer, comprising the step of administering to a patient a therapeutically effective amount of a perillyl alcohol derivative such as a perillyl alcohol ester, or an isoperillyl alcohol derivative such as an isoperillyl alcohol ester. The derivative may be a perillyl alcohol or an isoperillyl alcohol conjugated with a therapeutic agent such as valproic acid. The route of administration may vary, including inhalation, intranasal, oral, transdermal, intravenous, subcutaneous or intramuscular injection.

The present inventions provides drug-drug conjugates, drug-porphyrin conjugates, nanoparticles of the conjugates, as well as modified nanoparticles having PEGylated exteriors or encapsulated by red blood cell vesicles. The conjugates, nanoparticles and nanocarriers are useful for treating cancers and other diseases, as well as for imaging diseased tissue or organs.