Disclosed herein are synthesis and use of covalent inhibitors selective for Transcriptional Enhancer Factor TEF-1 (TEAD1), which can be used for treatment of cancers such as glioblastoma, gastric cancer, colorectal cancer, pancreatic ductal adenocarcinoma (PDAC), and malignant pleural mesothelioma (MPM). Further disclosed herein are pharmaceutical compositions including the TEAD1 inhibitor and methods of treating cancers using the same.

Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic, cardiovascular, fibrotic, autoimmune/chronic inflammatory diseases, cystic fibrosis, various cancers, neurodegenerative diseases, lipid storage disorders, and ischemia/reperfusion injury, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.

The invention relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

The invention relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic, cardiovascular, fibrotic, autoimmune/chronic inflammatory diseases, cystic fibrosis, various cancers, neurodegenerative diseases, lipid storage disorders, and ischemia/reperfusion injury, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.

A compound represented by the following formula (0).

##STR00001##

(In the above formula (0), R.sup.X represents a 2n.sup.A-valent group having 1 to 70 carbon atoms or a single bond; each R.sup.1A independently represents any of an alkyl group having 1 to 30 carbon atoms and optionally having a substituent, an aryl group having 6 to 30 carbon atoms and optionally having a substituent, a crosslinkable group having 2 to 30 carbon atoms and optionally having a substituent, an alkoxy group having 1 to 30 carbon atoms and optionally having a substituent, a maleamic acid group having 4 to 30 carbon atoms and optionally having a substituent, a maleimide group having 4 to 30 carbon atoms and optionally having a substituent, a halogen atom, a nitro group, an amino group having 0 to 30 carbon atoms and optionally having a substituent, a carboxyl group, a thiol group and a hydroxy group, wherein, when R.sup.1A is any of the alkyl group, the aryl group, the crosslinkable group and the alkoxy group, at least one bond selected from the group consisting of an ether bond, a ketone bond and an ester bond is optionally contained, and at least one R.sup.1A is any of a maleamic acid group having 4 to 30 carbon atoms and optionally having a substituent and a maleimide group having 4 to 30 carbon atoms and optionally having a substituent; X represents an oxygen atom or a sulfur atom, or is optionally not present; each R independently represents any of a benzene ring, a naphthalene ring and an anthracene ring; each m is independently an integer of 0 to 9, wherein at least one m is an integer of 1 to 9; and n.sup.A is an integer of 1 to 4.)

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity.

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity.

Shown is a compound represented by formula (1). For example, R.sup.1 is alkyl having 1 to 15 carbons; MES is a mesogen group having at least one ring; Sp.sup.1 is a single bond or alkylene having 1 to 10 carbons; M.sup.1 is methyl; and R.sup.2, M.sup.2 and M.sup.3 are hydrogen. ##STR00001##

Shown is a compound represented by formula (1). For example, R.sup.1 is alkyl having 1 to 15 carbons; MES is a mesogen group having at least one ring; Sp.sup.1 is a single bond or alkylene having 1 to 10 carbons; M.sup.1 is methyl; and R.sup.2, M.sup.2 and M.sup.3 are hydrogen. ##STR00001##