The present invention relates to the compound having Formula (I) or pharmaceutically acceptable salts or solvates thereof, and its use in treating and/or preventing a Tauopathy. ##STR00001##

The invention provides dimeric quinacrine derivatives and related compounds and compositions, methods of treatment and syntheses. The novel compounds exhibit unexpected anticancer activity and are useful in the treatment of a variety of autophagy-related disorders.

The invention provides dimeric quinacrine derivatives and related compounds and compositions, methods of treatment and syntheses. The novel compounds exhibit unexpected anticancer activity and are useful in the treatment of a variety of autophagy-related disorders.

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):(I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A is a heterocyclic or heteroaryl ring, and R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, A, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. ##STR00001##

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):(I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A is a heterocyclic or heteroaryl ring, and R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, A, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. ##STR00001##

Large-pore mesoporous silica nanoparticles (MSN) were prepared and functionalized to serve as a robust and biocompatible delivery platform for platinum-acridine (PA) anticancer agents. The material showed a high loading capacity for the dicationic, hydrophilic hybrid agent [PtCl(en)(N-[acridin-9-ylaminoethyl]-N-methylropionamidine)] dinitrate salt (P1 Al) and virtually complete retention of payload at neutral pH in a high-chloride buffer. In acidic media mimicking the pH inside the cells' lysosomes, rapid, burst-like release of P1 A1 from the nanoparticles is observed. Coating of the materials in phospholipid bilayers resulted in nanoparticles with greatly improved colloidal stability. The lipid and carboxylate- modified nanoparticles containing 40 wt. % drug caused S phase arrest and inhibited cell proliferation in pancreatic cancer cells at submicromolar concentrations similar to carrier-free P1A1. One feature of the nanoparticle-delivered P1A1 was that the payload did not escape from the acidified lysosomal vesicles into the cytoplasm, but was shuttled to the nuclear membrane and released into the nucleus.

The present invention provides therapeutic strategies for treatment of severe debilitating diseases associated with IFN-I due to cGAS activation. In one aspect, the invention provides compounds of Formula (I): [Formula should be inserted here] and pharmaceutical uses thereof. In another aspect, the invention provides methods for treating an autoimmune disease or a monogenic disorder by administering an effective amount of a compound of Formula (I). ##STR00001##

The present invention provides therapeutic strategies for treatment of severe debilitating diseases associated with IFN-I due to cGAS activation. In one aspect, the invention provides compounds of Formula (I): [Formula should be inserted here] and pharmaceutical uses thereof. In another aspect, the invention provides methods for treating an autoimmune disease or a monogenic disorder by administering an effective amount of a compound of Formula (I). ##STR00001##

We disclose novel asymmetric bis-acridines with antitumor activity. These compounds are useful for use in pharmaceuticals, particularly in the treatment or the prevention of neoplasms.

We disclose novel asymmetric bis-acridines with antitumor activity. These compounds are useful for use in pharmaceuticals, particularly in the treatment or the prevention of neoplasms.