330-81-4Relevant articles and documents
GRANZYME B DIRECTED IMAGING AND THERAPY
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Page/Page column 82; 105, (2019/09/04)
Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
Pyrazole-based potent inhibitors of GGT1: Synthesis, biological evaluation, and molecular docking studies
Mansha, Muhammad,Kumari, Udayappan Udhaya,Cournia, Zoe,Ullah, Nisar
, p. 666 - 676 (2016/09/14)
In this study, a series of pyrazole-based structural analogues of GGTI-DU40 (1) have been synthesized and biologically evaluated for geranylgeranyltransferase 1 (GGT1) and farnesyltransferase (FT) inhibition. The screening results revealed that 2 (IC50?=?2.4?μM) and 5 (IC50?=?3.1?μM) are potent GGT1 inhibitors (GGTIs), possessing higher inhibitory activity compared to the control compound 1 (IC50?=?3.3?μM). The anti-proliferative efficacy of these compounds was further assayed against MDA-MB-231?cells which indicated a significantly higher activity of 2 (IC50?=?7.6?μM) compared to 1 (IC50?=?23.0?μM). To examine the capacity of the synthesized compounds to inhibit GGT1 in an intact cell, western blot analysis was performed on the MDA-MB-231?cell line, which revealed very high inhibitory cellular activity of 2 and 5 and demonstrated their capacity to inhibit prenylation of endogenous proteins. Molecular docking studies of 2 against the crystal structure of GGT1 complexed with a geranylgeranyl pyrophosphate (GGPP) Analog and a CaaX (C?=?cysteine, aa?=?aliphatic amino acids, and X?=?any amino acid) portion of the KKKSKTKCVIL peptide substrate revealed several hydrogen bonding interactions and π-π contacts between 2 and the binding pocket of GGT1. Together these data suggest that compound 2 could proceed to in?vivo investigation to further assess its efficacy and cytotoxicity.
Electron-donating and rigid p-stereogenic bisphospholane ligands for highly enantioselective rhodium-catalyzed asymmetric hydrogenations
Zhang, Xiaowei,Huang, Kexuan,Hou, Guohua,Cao, Bonan,Zhang, Xumu
supporting information; experimental part, p. 6421 - 6424 (2010/12/19)
More electron donating, more rigid: A new highly electron-donating P-stereogenic bisphospholane ligand (ZhangPhos) was synthesized in a practical and highly enantioselective manner from a commercially available chiral source. Better or comparable enantioselectivities and reactivities than TangPhos were achieved in rhodium-catalyzed hydrogenation of various functionalized olefins (see scheme; nbd=3,5-norbornadiene). Copyright