Biomaterial Database

Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A). 2017

Maria Teresa Borrello, and Benjamin Schinor, and Katharina Bartels, and Hanae Benelkebir, and Sara Pereira, and Wafa T Al-Jamal, and Leon Douglas, and Patrick J Duriez, and Graham Packham, and Günter Haufe, and A Ganesan

School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom.

We report a series of tranylcypromine analogues containing a fluorine in the cyclopropyl ring. A number of compounds with additional m- or p-substitution of the aryl ring were micromolar inhibitors of the LSD1 enzyme. In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement.

UI	MeSH Term	Description	Entries
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006657	Histones	Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.	Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014191	Tranylcypromine	A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)	Jatrosom,Parnate,Transamine,Tranylcypromine Sulfate,trans-2-Phenylcyclopropylamine,Sulfate, Tranylcypromine,trans 2 Phenylcyclopropylamine
D015415	Biomarkers	Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc.	Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109	Cell Proliferation	All of the processes involved in increasing CELL NUMBER including CELL DIVISION.	Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051940	B7-2 Antigen	A costimulatory ligand glycoprotein that contains a C2 and V-type IMMUNOGLOBULIN DOMAIN. It is expressed by ANTIGEN-PRESENTING CELLS and binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.	Antigens, CD86,B7-2 Costimulatory Molecule,CD86 Antigens,Antigen, B7-2,B70 Costimulatory Molecule,CD86 Antigen,Early T Cell Costimulatory Molecule 1,Antigen, B7 2,Antigen, CD86,B7 2 Antigen,Costimulatory Molecule, B7-2,Costimulatory Molecule, B70
D054879	Halogenation	Covalent attachment of HALOGENS to other compounds.	Bromination,Chlorination,Fluorination,Iodination,Iodation
D056466	Histone Demethylases	Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.	Histone Demethylase,Histone Lysine Demethylase,Histone Arginine Demethylases,Histone Lysine Demethylases,Arginine Demethylases, Histone,Demethylase, Histone,Demethylase, Histone Lysine,Demethylases, Histone,Demethylases, Histone Arginine,Demethylases, Histone Lysine,Lysine Demethylase, Histone,Lysine Demethylases, Histone