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The Reaction Mechanism
Published in D. B. Keech, J. C. Wallace, Pyruvate Carboxylase, 2018
Additional information relevant to the sequence of events occurring at the second subsite was obtained by Goodall et al.323 during their investigation of the factors that influence the translocation of carboxybiotin between the two subsites of pyruvate carboxylase. They showed that the presence of compounds such as hydroxypyruvic acid (Structure J), oxamic acid (Structure K), and glyoxylic acid (Structure L) readily caused the decarboxylation of carboxybiotin. This was interpreted to indicate that these compounds were effective signals for attracting the carboxybiotin complex out of the first subsite and into the second subsite, and since these compounds were not carboxylated, the carboxybiotin spontaneously decarboxylated. In the case of oxamate and glyoxylate, carbanion formation could not have occurred.
Targeting glucose metabolism to develop anticancer treatments and therapeutic patents
Published in Expert Opinion on Therapeutic Patents, 2022
Yan Zhou, Yizhen Guo, Kin Yip Tam
Although there is still no single HK2 inhibitor for clinical cancer treatment, combination treatment of HK2 inhibitors with other compounds targeting elsewhere in glycolysis at this time could be an ideal solution for these problems because decreasing the dosing concentration of each compound reduces the potential toxicity. Similarly, there are patents reporting the combined use of novel inhibitors for PDK and LDHA, as well as with other known anticancer agents. Indeed, it was found that some of the recent inventions largely focused on various drug combination therapies or prodrugs with the specific aims to enhance the anticancer effects while modulating cancer cell metabolism [63,69,89]. It is expected that drug combinations with, either two metabolic inhibitors or one metabolic inhibitor and one anticancer agent, are likely to exhibit synergistic anticancer effects and the reduced dose administration leads to less systemic toxicity, which may be advantageous in developing anticancer therapies. One promising avenue that could be pursued is well-designed prodrug. For example, the prodrug that links dichloroacetate and oxamate could quickly release DCA and oxamate in vivo and surprisingly exerted more potent effects than DCA plus oxamate, with reduced undesirable side effects [63].
Overexpression of long non-coding RNA urothelial carcinoma associated 1 causes paclitaxel (Taxol) resistance in colorectal cancer cells by promoting glycolysis
Published in Journal of Chemotherapy, 2021
Huijuan Shi, Kejun Li, Jinxin Feng, Xiangliang Zhang
Rabbit monoclonal antibody against hexokinase 2 was purchased from Cell Signaling Technology (#2867, Beverly, MA, USA). Rabbit monoclonal antibody against LDHA was purchased from Cell Signaling Technology (#3582, Beverly, MA, USA). Mouse monoclonal antibody against β-actin was purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA). 3-BrPA and Oxamate were purchased from Sigma-Aldrich (Shanghai, China). Paclitaxel was purchased from Sigma-Aldrich (Shanghai, China) and stored as a 20-mM solution in dimethyl sulfoxide (DMSO) at a final concentration of 0.1% (v/v) at 80˚C and diluted with DMEM before use.