Understanding the mechanisms by which compounds discovered using cell-based phenotypic screening strategies might exert their effects would be highly augmented by new approaches exploring their potential interactions with the genome. For example, altered androgen receptor (AR) transcriptional programs, including castration resistance and subsequent chromosomal translocations, play key roles in prostate cancer pathological progression, making the quest for identification of new therapeutic agents and an understanding of their actions a continued priority. Here we report an approach that has permitted us to uncover the sites and mechanisms of action of a drug, referred to as "SD70," initially identified by phenotypic screening for inhibitors of ligand and genotoxic stress-induced translocations in prostate cancer cells. Based on synthesis of a derivatized form of SD70 that permits its application for a ChIP-sequencing-like approach, referred to as "Chem-seq," we were next able to efficiently map the genome-wide binding locations of this small molecule, revealing that it largely colocalized with AR on regulatory enhancers. Based on these observations, we performed the appropriate global analyses to ascertain that SD70 inhibits the androgen-dependent AR program, and prostate cancer cell growth, acting, at least in part, by functionally inhibiting the Jumonji domain-containing demethylase, KDM4C. Global location of candidate drugs represents a powerful strategy for new drug development by mapping genome-wide location of small molecules, a powerful adjunct to contemporary drug development strategies.

© 2019. The American Astronomical Society. All rights reserved. Located at Dome A, the highest point of the Antarctic plateau, the Chinese Kunlun station is considered to be one of the best ground-based photometric sites because of its extremely cold, dry, and stable atmosphere. A target can be monitored from there for over 40 days without diurnal interruption during a polar winter. This makes Kunlun station a perfect site to search for short-period transiting exoplanets. Since 2008, an observatory has existed at Kunlun station, and three telescopes are working there. Using these telescopes, the AST3 project has been carried out over the last 6 yr with a search for transiting exoplanets as one of its key programs (CHESPA). In the austral winters of 2016 and 2017, a set of target fields in the southern continuous viewing zone (CVZ) of TESS were monitored by the AST3-II telescope. In this paper, we introduce the CHESPA and present the first data release containing photometry of 26,578 bright stars (). The best photometric precision at the optimum magnitude for the survey is around 2 mmag. To demonstrate the data quality, we also present a catalog of 221 variables with a brightness variation greater than 5 mmag from the 2016 data. Among these variables, 179 are newly identified periodic variables not listed in the AAVSO database (https://www.aavso.org/), and 67 are listed in the Candidate Target List. These variables will require careful attention to avoid false-positive signals when searching for transiting exoplanets. Dozens of new transiting exoplanet candidates will be released in a subsequent paper.

© 2019. The American Astronomical Society. All rights reserved. We report first results from the CHinese Exoplanet Searching Program from Antarctica (CHESPA) - a wide-field high-resolution photometric survey for transiting exoplanets carried out using telescopes of the AST3 (Antarctic Survey Telescopes times 3) project. There are now three telescopes (AST3-I, AST3-II, and CSTAR-II) operating at Dome A - the highest point on the Antarctic Plateau - in a fully automatic and remote mode to exploit the superb observing conditions of the site, and its long and uninterrupted polar nights. The search for transiting exoplanets is one of the key projects for AST3. During the austral winters of 2016 and 2017 we used the AST3-II telescope to survey a set of target fields near the southern ecliptic pole, falling within the continuous viewing zone of the TESS mission. The first data release of the 2016 data, including images, catalogs, and light curves of 26,578 bright stars (), was presented in Zhang et al. The best precision, as measured by the rms of the light curves at the optimum magnitude of the survey (), is around 2 mmag. We detect 222 objects with plausible transit signals from these data, 116 of which are plausible transiting exoplanet candidates according to their stellar properties as given by the TESS Input Catalog, Gaia DR2, and TESS-HERMES spectroscopy. With the first data release from TESS expected in late 2018, this candidate list will be timely for improving the rejection of potential false-positives.