-transparent.png){kind=logo}
Discovery of GNE-502 as an orally bioavailable and potent degrader for estrogen receptor positive breast cancer. 2021
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: Zbieg.Jason@gene.com.
Fulvestrant is an FDA-approved drug with a dual mechanism of action (MOA), acting as a full antagonist and degrader of the estrogen receptor protein. A significant limitation of fulvestrant is the dosing regimen required for efficacy. Due to its high lipophilicity and poor pharmacokinetic profile, fulvestrant needs to be administered through intramuscular injections which leads to injection site soreness. This route of administration also limits the dose and target occupancy in patients. We envisioned a best-in-class molecule that would function with the same dual MOA as fulvestrant, but with improved physicochemical properties and would be orally bioavailable. Herein we report our progress toward that goal, resulting in a new lead GNE-502 which addressed some of the liabilities of our previously reported lead molecule GNE-149.
Related Publications
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
April 2018,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
April 2017,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
December 2020,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
February 2023,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
June 2021,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
June 2023,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
September 2023,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
October 2015,
Anti-cancer drugs,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
March 2021,
Journal of medicinal chemistry,
Jason R Zbieg, and
Jun Liang, and
Jun Li, and
Robert A Blake, and
Jae Chang, and
Lori Friedman, and
Simon Goodacre, and
Steven J Hartman, and
Ellen Rei Ingalla, and
James R Kiefer, and
Tracy Kleinheinz, and
Sharada Labadie, and
Tommy Lai, and
Jiangpeng Liao, and
Nev McLean, and
Ciara Metcalfe, and
Vidhi Mody, and
Michelle Nannini, and
Daniel F Ortwine, and
Yingqing Ran, and
Nick Ray, and
Fabien Roussel, and
Amy Sambrone, and
Deepak Sampath, and
Maia Vinogradova, and
John Wai, and
Tao Wang, and
Kuen Yeap, and
Birong Zhang, and
Xiaoping Zheng, and
Yu Zhong, and
Xiaojing Wang
April 2023,
Journal of medicinal chemistry,
