Birinapant

Female 5–6-week-old NRG mice (Jackson labs stock #007799) were implanted with HCI-011 patient-derived xenograft (PDX) tumor fragments using a previously described protocol with estrogen supplementation (42 (link)). When tumors reached approximately 100 mm³, mice were randomized into treatment or control groups. Mice received either vehicle control (15% captisol IP, 3×/week for 5 weeks), birinapant (20 mg/kg IP, 3×/week for 5 weeks), fulvestrant (200 mg/kg subQ, 1×/week for 5 weeks), or the combination of birinapant and fulvestrant at the same doses as single agents. For birinapant treatment, birinapant (Medchem Express, HY-16591) was dissolved in 15% captisol at a concentration of 2 mg/mL (made fresh every time), and 100 μL/10 g mouse body weight was injected intraperitoneally. For fulvestrant treatment, 250 mg of fulvestrant (Selleck Chemicals, S1191) was dissolved in 0.5 mL DMSO, incubated at 37°C for 15 minutes and then diluted 1:20 with corn oil to give a final concentration of fulvestrant of 25 mg/mL (made fresh every time). 80 μL/10 g mouse body weight was injected subcutaneously. Animal experiments were all conducted in compliance with institutional guidelines and regulations after approval from the University of Utah Institutional Animal Care and Use Committee, under protocol 21-06008.

Gemcitabine (cat# S1714) and Cisplatin (cat# S1166) were purchased from Selleck Chemicals (Houston, TX, USA), and LCL161 (cat# HY-15518) and Birinapant (cat# HY-16591) were from purchased from MedChemExpress (Monmouth Junction, NJ, USA). Drug response tests were performed as previously described (17 (link)).