The present invention aims to provide a polymerizable compound that has high storage stability without causing crystal precipitation when added to a polymerizable composition and to provide a polymerizable composition containing the polymerizable compound. A polymer film produced by polymerization of the polymerizable composition has a low haze, high thickness uniformity, low occurrence of nonuniform orientation, high surface hardness, high adhesiveness, and good appearances and fewer orientation defects even after ultraviolet irradiation. The present invention also aims to provide a polymer produced by polymerization of the polymerizable composition and an optically anisotropic body produced from the polymer.

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein, R.sup.1, R.sup.2a, R.sup.2b, R.sup.3 and A are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

##STR00001##

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein, R.sup.1, R.sup.2a, R.sup.2b, R.sup.3 and A are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

##STR00001##

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

##STR00001##

The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

##STR00001##

The present invention relates to compounds of Formula (I) that target the MLH1 and/or PMS2 proteins that are components of the DNA Mismatch Repair (MMR) process:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.6 and R.sup.10 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which MLH1 and/or PMS2 activity is implicated.

The present invention relates to compounds of Formula (I) that target the MLH1 and/or PMS2 proteins that are components of the DNA Mismatch Repair (MMR) process:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.6 and R.sup.10 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which MLH1 and/or PMS2 activity is implicated.

Described herein is a contrast agent for administration to a subject. The contrast agent includes a targeting portion that includes a hydrazide functional group; a metal ion bound to a metal-complexable portion; and a linker joining the targeting portion and the metal-complexable portion of the contrast agent. The portion that is not bound to a metal ion localizes the contrast agent to necrotic tissue in the subject.