131372-64-0Relevant articles and documents
GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer
Liang, Jun,Zbieg, Jason R.,Blake, Robert A.,Chang, Jae H.,Daly, Stephen,Dipasquale, Antonio G.,Friedman, Lori S.,Gelzleichter, Thomas,Gill, Matthew,Giltnane, Jennifer M.,Goodacre, Simon,Guan, Jane,Hartman, Steven J.,Ingalla, Ellen Rei,Kategaya, Lorn,Kiefer, James R.,Kleinheinz, Tracy,Labadie, Sharada S.,Lai, Tommy,Li, Jun,Liao, Jiangpeng,Liu, Zhiguo,Mody, Vidhi,McLean, Neville,Metcalfe, Ciara,Nannini, Michelle A.,Oeh, Jason,O'Rourke, Martin G.,Ortwine, Daniel F.,Ran, Yingqing,Ray, Nicholas C.,Roussel, Fabien,Sambrone, Amy,Sampath, Deepak,Schutt, Leah K.,Vinogradova, Maia,Wai, John,Wang, Tao,Wertz, Ingrid E.,White, Jonathan R.,Yeap, Siew Kuen,Young, Amy,Zhang, Birong,Zheng, Xiaoping,Zhou, Wei,Zhong, Yu,Wang, Xiaojing
, p. 11841 - 11856 (2021)
Breast cancer remains a leading cause of cancer death in women, representing a significant unmet medical need. Here, we disclose our discovery efforts culminating in a clinical candidate, 35 (GDC-9545 or giredestrant). 35 is an efficient and potent selective estrogen receptor degrader (SERD) and a full antagonist, which translates into better antiproliferation activity than known SERDs (1, 6, 7, and 9) across multiple cell lines. Fine-tuning the physiochemical properties enabled once daily oral dosing of 35 in preclinical species and humans. 35 exhibits low drug-drug interaction liability and demonstrates excellent in vitro and in vivo safety profiles. At low doses, 35 induces tumor regressions either as a single agent or in combination with a CDK4/6 inhibitor in an ESR1Y537S mutant PDX or a wild-type ERα tumor model. Currently, 35 is being evaluated in Phase III clinical trials.
POLY(PHOSPHOESTERS) FOR DELIVERY OF NUCLEIC ACIDS
-
Paragraph 0401; 0404, (2020/09/15)
Disclosed are polymers comprising the moiety A, which is a moiety of formula I: and pharmaceutically acceptable salts thereof, wherein R, R1, R2, L, n1 and n2 are as defined herein. These polymers are useful for delivering nucleic acids to subject. These polymers and pharmaceutically acceptable compositions comprising such polymers and nucleic acids can be useful for treating various diseases, disorders and conditions.
ASH1L INHIBITORS AND METHODS OF TREATMENT THEREWITH
-
Page/Page column 196, (2017/12/01)
Provided herein are small molecule inhibitors of ASH1L activity and small molecules that facilitate ASH1L degradation and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.