54157-11-8Relevant articles and documents
Histone H4-based peptoids are inhibitors of protein arginine methyltransferase 1 (PRMT1)
Causey, Corey P.,DeMart, Megan K.,Knuckley, Bryan,Mann, Sarah A.,May, Braidy
, p. 2971 - 2980 (2020/09/01)
Methylation of arginine residues occurs on a number of protein substrates, most notably the N-terminal tails of histones, and is catalyzed by a family of enzymes called the protein arginine methyltransferases (PRMTs). This modification can lead to transcriptional activation or repression of cancer-related genes. To date, a number of inhibitors, based on natural peptide substrates, have been developed for the PRMT family of enzymes. However, because peptides are easily degraded in vivo, the utility of these inhibitors as potential therapeutics is limited. The use of peptoids, which are peptide mimetics where the amino acid side chain is attached to the nitrogen in the amide backbone instead of the α-carbon, may circumvent the problems associated with peptide degradation. Given the structural similarities, peptoid scaffolds may provide enhanced stability, while preserving the mechanism of action. Herein, we have identified that peptoids based on natural peptide substrates are not catalyzed to the product by PRMT1, but instead are inhibitors of this enzyme. Reducing the length of the peptoid reduces inhibition and suggest the residues distal from the site of modification are important for binding. Furthermore, a positive charge on the N-terminus helps promote binding and improves inhibition. Selectivity among family members is likely possible based on inhibition being moderately selective for PRMT1 over PRMT5 and provides a scaffold that can be used to develop pharmaceuticals against this class of enzymes.
Skin care
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Paragraph 0061; 0064, (2017/10/05)
PROBLEM TO BE SOLVED: To provide a skin care preparation suitable for a cosmetic (provided that quasi drugs are included) or the like, for detail, a skin care preparation having whitening effects, particularly preventive or improving effects against pigme
MELANIN PRODUCTION INHIBITOR
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Paragraph 0180 - 0184, (2015/12/17)
Disclosed is a melanin production inhibitor which has an excellent inhibitory activity on the production of melanin and is highly safe. The melanin production inhibitor is represented by general formula (1) (excluding clotrimazole) and/or a pharmacologically acceptable salt thereof. In the formula, A1, A2 and A3 are independently selected from a hydrogen atom, an aryl group which may have a substituent, and an aromatic heterocyclic group which may have a substituent. At least one of A1, A2 and A3 is selected from the aryl group and the aromatic heterocyclic group, the total number of carbon atoms contained in A1, A2 and A3 is 6 to 50 and, when at least two of A1, A2 and A3 represent the aryl groups or the aromatic heterocyclic groups, the adjacent two aryl or aromatic heterocyclic groups may be bound to each other via an alkyl chain or an alkenyl chain to form a ring; m represents an integer of 0 to 2; X represents a hetero atom, a hydrogen atom, or a carbon atom; R1 and R2 are independently selected from a hydrogen atom and an oxo group. When one of R1 and R2 is an oxo group, the other is not present. R3 is selected from a hydrogen atom, and a C1-8 hydrocarbon group in which one or some of hydrogen atoms or carbon atoms may be substituted by a hetero atom or hetero atoms. The number of R3's present in the compound corresponds to X and, when two or more R3's are present, the R3's are independently present and the adjacent two R3's may be bound to each other to form, together with X, a ring, and the terminal of R3 may be bound to a carbon atom to which A1, A2 and A3 are bound, thereby forming a ring.
