@article{a353317625d84b84bb46e7ddb0dcf8b8,
title = "A Novel 2-Carbon-Linked Dimeric Artemisinin With Potent Antileukemic Activity and Favorable Pharmacology",
abstract = "Acute myeloid leukemia (AML) remains a devastating disease, with low cure rates despite intensive standard chemotherapy regimens. In the past decade, targeted antileukemic drugs have emerged from research efforts. Nevertheless, targeted therapies are often effective for only a subset of patients whose leukemias harbor a distinct mutational or gene expression profile and provide only transient antileukemic responses as monotherapies. We previously presented single agent and combination preclinical data for a novel 3-carbon-linked artemisinin-derived dimer (3C-ART), diphenylphosphate analog 838 (ART838), that indicates a promising approach to treat AML, given its demonstrated synergy with targeted antileukemic drugs and large therapeutic window. We now report new data from our initial evaluation of a structurally distinct class of 2-carbon-linked dimeric artemisinin-derived analogs (2C-ARTs) with prior documented in vivo antimalarial activity. These 2C-ARTs have antileukemic activity at low (nM) concentrations, have similar cooperativity with other antineoplastic drugs and comparable physicochemical properties to ART838, and provide a viable path to clinical development.",
keywords = "antineoplastics, artemisinins, leukemia, sorafenib, venetoclax (ABT-199)",
author = "Kagan, {Amanda B.} and Moses, {Blake S.} and Mott, {Bryan T.} and Ganesha Rai and Anders, {Nicole M.} and Rudek, {Michelle A.} and Civin, {Curt I.}",
note = "Funding Information: This study was supported in part by the Maryland Technology Development Corporation (TEDCO) MII Innovation Grant 131175, an award from the Emmert Hobbs Foundation Endowment (BSM), and the Clinical Pharmacology Training Program grant (ABK, NIH T32GM066691). The project described was also supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH P30CA006973 (NA, MR) and UL1TR003098 (NA, MR), Shared Instrument Grant S10RR026824 (MR). Grant Number UL1TR003098 is from the National Center for Advancing Translational Sciences (NCATS), a component of the NIH, and NIH Roadmap for Medical Research. Funding for the study described in this publication was provided by Geminus Therapeutics LLC. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Funding Information: This study was supported in part by the Maryland Technology Development Corporation (TEDCO) MII Innovation Grant 131175, an award from the Emmert Hobbs Foundation Endowment (BSM), and the Clinical Pharmacology Training Program grant (ABK, NIH T32GM066691). The project described was also supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH P30CA006973 (NA, MR) and UL1TR003098 (NA, MR), Shared Instrument Grant S10RR026824 (MR). Grant Number UL1TR003098 is from the National Center for Advancing Translational Sciences (NCATS), a component of the NIH, and NIH Roadmap for Medical Research. Funding for the study described in this publication was provided by Publisher Copyright: Copyright {\textcopyright} 2022 Kagan, Moses, Mott, Rai, Anders, Rudek and Civin.",
year = "2022",
month = jan,
day = "11",
doi = "10.3389/fonc.2021.790037",
language = "English (US)",
volume = "11",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media S. A.",
}