Provided is a drug containing a liver targeting specific ligand and a thyroid hormone receptor agonist in its structure, which is a new drug structure formed by linking the liver targeting specific ligand with the thyroid hormone receptor agonist through a branched chain, a linker and a linking chain. Thyroid hormone receptors (TRs) are divided into two subtypes, TR-α and TR-β, wherein, TR-β is mainly expressed in liver, and TR-α is mainly expressed in heart, nervous system, etc. In certain embodiments, it is envisaged that the provided drug has the action of liver targeting, can specifically bring the thyroid hormone receptor agonist into liver, without entering heart and other issues, and may thereby avoid side effects caused by the action of the thyroid hormone receptor agonist on other issues, and maintain its therapeutic efficacy in the treatment of lipid metabolism disorders and related complications.

The disclosure provides pharmaceutical formulations of the compound of Formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof.

The present application discloses an acid labile lipophilic molecular conjugate of cancer chemotherapeutic agents and methods for reducing or substantially eliminating the side effects of chemotherapy associated with the administration of a cancer chemotherapeutic agent to a patient in need thereof.

The syntheses of two phosphoramidite building blocks based on BNSF and BNSMB structures are disclosed. Furthermore, some common molecular intermediates have been designed and linked to the central biphenyl core of the two molecules, resulting in a versatile and cost-effective design. These compounds can be effectively introduced to DNA oligonucleotides via the well-established standard cyanoethylphosphoramidite chemistry on the nucleic acid synthesizer. Fragmentation of these BNSF- and BNSMB-functionalized DNA strands is achieved by both one-photon and two-photon photolysis of photoliable bonds of [2-(2-nitrophenyl)propoxy]carbonyl groups on BNSF and BNSMB molecules respectively, resulting in two short pieces of single-stranded DNAs. The versatile design and facile synthesis of these two-photon photocleavage phosphoramidite molecules are beneficial to synthetic chemists and photochemists for the development of new caged compounds which enables to introduce into oligonucleotides as light-triggered carriers via solid-phase synthesis for a wide range of applications in materials science, polymer, chemistry, biology and DNA nanoecthnology.

The syntheses of two phosphoramidite building blocks based on BNSF and BNSMB structures are disclosed. Furthermore, some common molecular intermediates have been designed and linked to the central biphenyl core of the two molecules, resulting in a versatile and cost-effective design. These compounds can be effectively introduced to DNA oligonucleotides via the well-established standard cyanoethylphosphoramidite chemistry on the nucleic acid synthesizer. Fragmentation of these BNSF- and BNSMB-functionalized DNA strands is achieved by both one-photon and two-photon photolysis of photoliable bonds of [2-(2-nitrophenyl)propoxy]carbonyl groups on BNSF and BNSMB molecules respectively, resulting in two short pieces of single-stranded DNAs. The versatile design and facile synthesis of these two-photon photocleavage phosphoramidite molecules are beneficial to synthetic chemists and photochemists for the development of new caged compounds which enables to introduce into oligonucleotides as light-triggered carriers via solid-phase synthesis for a wide range of applications in materials science, polymer, chemistry, biology and DNA nanoecthnology.

High penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas HPCs of NSAIA, for example, have demonstrated indications such as treating hair loss. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

High penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas HPCs of NSAIA, for example, have demonstrated indications such as treating hair loss. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

Provided herein, inter alia, are methods and compounds for inhibiting K-Ras and for treating cancer.

The present disclosure provides one or more amino lipids such as an amino lipids containing a sulfonic acid or sulfonic acid derivative of the formulas: ##STR00001##
wherein the variables are as defined herein. These amino lipids may be used in compositions with one or more helper lipids and a nucleic acid therapeutic agent. These compositions may be used to treat a disease or disorder such as cancer, cystic fibrosis, or other genetic diseases.

Provided herein are, inter alia, nucleic acid-peptide conjugates including a non-cell penetrating protein attached at its C-terminus to a phosphorothioate nucleic acid. Attachment of the phosphorothioate nucleic acid to the non-cell penetrating protein conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating peptide. The nucleic acid-peptide conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer, inflammatory disease, pain, and viral infection.