173606-54-7Relevant articles and documents
Design, Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders
Iida, Tetsuya,Itoh, Yukihiro,Takahashi, Yukari,Yamashita, Yasunobu,Kurohara, Takashi,Miyake, Yuka,Oba, Makoto,Suzuki, Takayoshi
, p. 1609 - 1618 (2021)
Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b, which was designed based on compound 1, degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1. These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.
A bicyclic pentapeptide-based highly potent and selective pan-SIRT1/2/3 inhibitor harboring Nε-thioacetyl-lysine
Li, Renwu,Sun, Xun,Yan, Lingling,Zheng, Weiping
, (2020)
Past few years have seen an active pursuit of the inhibitors for the deacylation catalyzed by the seven human sirtuins (i.e. SIRT1-7) as valuable chemical biological/pharmacological probes of this enzymatic deacylation and lead compounds for developing novel therapeutics for human diseases. In the current study, we prepared eight monocyclic and one bicyclic analogs of a linear pentapeptide-based potent (sub-μM IC50’s) pan-SIRT1/2/3 inhibitor Zheng laboratory discovered recently that harbors the catalytic mechanism-based SIRT1/2/3 inhibitory warhead Nε-thioacetyl-lysine at its central position. We found that the bicyclic analog exhibited largely comparable SIRT1/2/3 inhibitory potencies to those of the parent linear pentapeptide, however, the former is proteolytically much more stable than the latter. Moreover, the bicyclic analog displayed very weak inhibition against SIRT5/6/7, was cell permeable, and exhibited an anti-proliferative effect on the human SK-MEL-2 melanoma cells. This bicyclic analog could be a lead for the future development of more potent and still selective pan-SIRT1/2/3 inhibitors whose use in studies on human sirtuin biology, pharmacology, and medicinal chemistry could complement with the use of the potent inhibitors selective for a single human sirtuin.
Synthesis and evaluation of tamoxifen derivatives with a long alkyl side chain as selective estrogen receptor down-regulators
Shoda, Takuji,Kato, Masashi,Harada, Rintaro,Fujisato, Takuma,Okuhira, Keiichiro,Demizu, Yosuke,Inoue, Hideshi,Naito, Mikihiko,Kurihara, Masaaki
, p. 3091 - 3096 (2015)
Abstract Estrogen receptors (ERs) play a major role in the growth of human breast cancer cells. An antagonist that acts as not only an inhibitor of ligand binding but also an inducer of the down-regulation of ER would be useful for the treatment for ER-po
Labeling study of avidin by modular method for affinity labeling (MoAL)
Nakanishi, Shuichi,Tanaka, Hiroyuki,Hioki, Kazuhito,Yamada, Kohei,Kunishima, Munetaka
, p. 7050 - 7053 (2010)
We studied the specific labeling of avidin with biotinylated modular ligand catalysts via MoAL, which we recently established. The labeling yield was found to depend on the linker length connecting the catalytic site to biotin in the modular ligand catalyst 1, and the maximum yield was obtained with 1d possessing octamethylene linker. The labeling reaction reached a maximum rate with only 4 equiv of the ligand catalyst. Presumably, all the subunits of avidin with homotetrameric structure formed a stable complex with 4 equiv of the catalyst because of the extremely high affinity. The ligand catalyst bound to avidin first catalyzed N-triazinylation of the -amino group of Lys111, and the resulting regenerated catalyst then catalyzed the reaction of Asp108 and CDMT.
De-novo designed β-lysine derivatives can both augment and diminish the proliferation rates of E. coli through the action of Elongation Factor P
Connon, Stephen J.,Ghanim, Magda,Kelly, Vincent P.,McDonnell, Ciara M.,Mike Southern, J.
supporting information, (2022/01/24)
An investigation into the effect of modified β-lysines on the growth rates of eubacterial cells is reported. It is shown that the effects observed are due to the post translational modification of Elongation Factor P (EFP) with these compounds catalysed b
Towards the development of a targeted albumin-binding radioligand: Synthesis, radiolabelling and preliminary in vivo studies
Driver, Cathryn Helena Stanford,Ebenhan, Thomas,Szucs, Zoltan,Parker, Mohammed Iqbal,Zeevaart, Jan Rijn,Hunter, Roger
, p. 53 - 66 (2021/02/09)
Introduction: The compound named 4-[10-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanamido)decyl]-11-[10-(β,D-glucopyranos-1-yl)-1-oxodecyl]-1,4,8,11-tetraazacyclotetradecane-1,8-diacetic acid is a newly synthesised molecule capable of binding in vivo to
RADIOPHARMACEUTICAL CONJUGATE
-
Page/Page column 40, (2016/04/20)
This invention relates new radiopharmaceutical conjugates for use in improved methods of diagnosis and treatment of cancer. The radiopharmaceutical conjugate comprises, in sequence: a metabolite that targets tumour cells, bound to a chelating agent capable of containing a radionuclide.bound to a linker capable of binding with an EPR agent in vitro or in vivo; or a chelating agent capable of containing a radionuclide, bound to a metabolite that targets tumour cells, bound to a linker capable of binding with an EPR agent in vitro or in vivo. The radiopharmaceutical conjugates of the present invention provide active and passive targeted radionuclide delivery systems that can help to improve the biodistribution and pharmacological toxicity of the radiopharmaceuticals used for the diagnosis and therapy of cancer.
Structure-activity relationship of C5-curcuminoids and synthesis of their molecular probes thereof
Yamakoshi, Hiroyuki,Ohori, Hisatsugu,Kudo, Chieko,Sato, Atsuko,Kanoh, Naoki,Ishioka, Chikashi,Shibata, Hiroyuki,Iwabuchi, Yoshiharu
supporting information; scheme or table, p. 1083 - 1092 (2010/04/24)
A series of novel analogues of 1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-(1E,4E)-1,4-dien-3-one (C5-curcumin), which is a natural analogue of curcumin isolated from the rhizomes of Curcuma domestica Val. (Zingiberacea), were synthesized and evaluated for their cytotoxicities against human colon cancer cell line HCT-116 to conclude the SAR of C5-curcuminoids for further development of their use in cancer chemotherapy: (1) Bis(arylmethylidene)acetone serves as a promising skeleton for eliciting cytotoxicity. (2) The 3-oxo-1,4-pentadiene structure is essential for eliciting cytotoxicity. (3) As for the extent of the aromatic substituents, hexasubstituted compounds exhibit strong activities, in which 3,4,5-hexasubstitution results in the highest potency. (5) The symmetry between two aryl rings is not an essential requirement for bis(arylmethylidene)acetones to elicit cytotoxicity. (6) para-Positions allows the installation of additional functional groups for use as molecular probes. By taking advantage of the SAR diagram, we have elaborated several advanced derivatives having GI50 of single-digit micromolar potencies that will function as molecular probes to target and/or report key biomolecules interacting with curcumin and C5-curcumin.
Synthesis of medium ring lactams via cyclization reactions using polymer bound HOBT as catalyst
Huang,Wei, Huang,Kalivretenos,Kalivretenos, Aristotle G.
, p. 9113 - 9116 (2007/10/02)
The synthesis of medium ring lactams (7-, 9-, 11- and 13-membered rings) via cyclization reactions mediated by polymer bound 1-hydroxybenzotriazole (HOBT) is reported.
