I am looking for info from anyone on these boards that has any knowledge of the chemical compound TDZD-8 (4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione).
I stumbled on this compound from an article Scuba had linked a few months ago and began doing my own research on it. It appears that this compound kills LSC's and progenitor cells and has been known to do this since at least 2007. I have been unable to find any evidence of this being taken to trials and the only company I found that is pursuing it currently is a little unknown company called Panther Biotechnology (http://pantherbiotechnology.com/) whose stock is currently trading at $0.94. The compound appears to be in use or studied for other things also (see below). If you have anything to add, it would be much appreciated.
Here are some excerpts from articles I have dug up in my research:
Studies of TDZD-8 were performed to determine the effects on different types of leukemiacells taken from patients (AML, bcCML, CLL and ALL), and on normal blood cells as well.All forms of leukemia cells were strongly inhibited and induced to die by TDZD-8,however, there was minimal effect on normal blood cells.This pattern of selectivity continues with the third agent, TDZD-8, which is lethal onlyto the leukemic population.
Rapid and selective death of leukemia stem and progenitor cells induced by the compound4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8).Leukemia is thought to arise from malignant stem cells, which have been described foracute and chronic myeloid leukemia (AML and CML) and for acute lymphoblastic leukemia(ALL). Leukemia stem cells (LSCs) are relatively resistant to current chemotherapy andlikely contribute to disease relapse and progression. Consequently, the identificationof drugs that can efficiently eradicate LSCs is an important priority. In the presentstudy, we investigated the antileukemia activity of the compound TDZD-8. Analysis ofprimary AML, blast crisis CML (bcCML), ALL, and chronic lymphoblastic leukemia (CLL)specimens showed rapid induction of cell death upon treatment with TDZD-8. In addition,for myeloid leukemias, cytotoxicity was observed for phenotypically primitive cells, invitro colony-forming progenitors, and LSCs as defined by xenotransplantation assays. Incontrast, no significant toxicity was observed for normal hematopoietic stem andprogenitor cells. Notably, cell death was frequently evident within 2 hours or less ofTDZD-8 exposure. Cellular and molecular studies indicate that the mechanism by whichTDZD-8 induces cell death involves rapid loss of membrane integrity, depletion of freethiols, and inhibition of both the PKC and FLT3 signaling pathways. We conclude thatTDZD-8 uses a unique and previously unknown mechanism to rapidly target leukemia cells,including malignant stem and progenitor populations.
TDZD-8 is a non-ATP competitive inhibitor of GSK-3β.It is widely studied as a cytoprotective agent to treat septicand nonseptic shock, lung injury, arthritis, spinal cordinjury, colitis and Alzheimer disease. Guzman et al. exploresanother functional facet of TDZD-8, namely selectivelykilling AML-stem/progenitor cells. Cellular and molecularstudies indicate that its mode-of-action is correlated withrapid loss of membrane integrity, depletion of free thiols/rapid ROS generation and inhibition of both the PKCand FLT3 signaling pathways. It should be noted thatTDZD-8 induces cell-death effects not only on AML,but also chronic myeloid leukemia (CML) and acutelymphoblastic leukemia (ALL) (25).From:Reactive oxygen species in eradicating acute myeloid leukemicstem cellsHui Zhang1,2, Hai Fang1, Kankan Wang1