The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.

The present disclosure provides certain tricyclic compounds that are histone methyltransferases G9a and/or GLP inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of G9a and/or GLP such as cancers and hemoglobinopathies (e.g., beta-thalassemia and sickle cell disease). Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

The application is drawn to radiohalogen prosthetic moieties and precursors thereof and to radiolabeled biomolecules comprising such radiohalogen prosthetic moieties. The biomolecules have an affinity for particular types of cells and may specifically bind a certain cell, such as a cancer cell. Relevant biomolecules include antibodies, monoclonal antibodies, antibody fragments, peptides, other proteins, nanoparticles, aptamers, and pharamacological moieties used to target prostate-specific membrane antigen (PSMA).

The application is drawn to radiohalogen prosthetic moieties and precursors thereof and to radiolabeled biomolecules comprising such radiohalogen prosthetic moieties. The biomolecules have an affinity for particular types of cells and may specifically bind a certain cell, such as a cancer cell. Relevant biomolecules include antibodies, monoclonal antibodies, antibody fragments, peptides, other proteins, nanoparticles, aptamers, and pharamacological moieties used to target prostate-specific membrane antigen (PSMA).

The present invention provides a method of imaging a subject's lung which comprises contacting the subject's lung with a matrix metalloproteinase inhibitor labeled with a radioisotope under conditions such that the inhibitor binds to matrix metalloproteinase in the lung, and then imaging the radiolabeled inhibitor bound to matrix metalloproteinase in the subject's lung. The invention also provides Ro 32-3555 labeled with a radioisotope.

The present invention provides a method for the synthesis of an injectable composition comprising a [.sup.18F]-labelled pyridaben derivative that is advantageous over prior methods. In particular, the method of the present invention comprises a method of radiosynthesis that permits a more facile purification using solid phase extraction (SPE).

The present invention provides a cassette for determining optimised solid phase extraction (SPE) purification conditions, wherein said cassette comprises: (i) a flowpath comprising a first end and a second end; and (ii) a plurality of valves oriented along said flowpath, wherein each of said plurality of valves is selectively fluidly connected to one of a number of components, wherein said components comprise: (a) 1-5 composition vials; (b) 1-3 SPE cartridges; (c) 4-10 solvent vials; (d) a water vial; and (e) a transfer line.

The present invention also provides a method for determining optimised SPE purification conditions for a compound from a composition, the method comprising: (i) provision of a cassette as defined in any of claims 1 to 7; (ii) the cassette comprising a composition of the compound in said composition vial(s) or addition of such a composition to said crude reaction vial(s); (iii) passing an aliquot of said composition into each of said 1-3 SPE cartridges; (iv) passing a particular combination of aliquots of solvent from at least 4 of said 4-10 solvent vials into one or more of the SPE cartridges, wherein the solvent in each of said 4-10 solvent vials is either a different solvent or the same solvent at different concentration; (v) eluting the compound to be purified from the or each SPE cartridge; (vi) evaluating the eluted products of step (v); and (vii) determining the optimised purification conditions by comparing the eluted products of step (v) from each cartridge and each solvent.

This invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT.sub.2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D.sub.1/D.sub.2 receptor signaling systems, and/or the treatment of residual symptoms.

The present disclosure relates generally to LRRK2 inhibitors, or a pharmaceutically acceptable salt, deuterated analog, prodrug, tautomer, stereoisomer, or mixture of stereoisomers thereof, and methods of making and using thereof.

Disclosed are methods and systems for hydrogen isotope exchange of organic molecules that can be carried out with no alteration in the chemical structure of the organic molecules. Methods can be utilized to incorporate a particular hydrogen isotope on an organic molecule (e.g., deuteration or tritiation) or to remove a particular hydrogen isotope from an organic molecule (e.g., detritiation).