Torkinib

Cerulein (40 μg/kg or 5 μg/mouse), KRIBB11 (mainly 2 μM for cells and 50 mg/kg for mice), erlotinib (2 μM for cells and 100 mg/kg for mice), selumetinib (100 nM for cells) and torkinib (50 nM for cells) were purchased from MedChem Express (Monmouth Junction, NJ, USA). Recombinant human epidermal growth factor (EGF mainly 20 ng/ml for cells) and transforming growth factor alpha (mainly TGFα 50 ng/ml for cells) were purchased from PeproTech (Rocky Hill, NJ, USA). All reagents were stored according to the manufacturer’s instructions.

The mTOR inhibitor PP242 (torkinib, purity 97.75%) was purchased form MedChemExpress (NJ, USA). Internal standards (ISs), reserpine, and 1-Hexadecanoyl (d₃₁)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (PC(16:0/18:1)-d₃₁) and arachidonic acid-d₈ were purchased from Sigma-Aldrich Chemical Co. (St. Louis, MO. USA) and Avanti Polar Lipids (Alabaster, AL, USA), respectively. Formic acid, ammonium acetate and 10% neutral buffered formalin solution were purchased from the Sigma-Aldrich Chemical Co. (St. Louis, MO, USA). Ultrapure water (18.2 MΩ cm) was generated using a Milli-Q apparatus from Millipore (Milford, MA, USA). All other chemicals were of highest analytical grades and HPLC grade organic solvents were used for the preparation of mobile phases and supplied by Burdick & Jackson (SK chemicals, Ulsan, Korea).

Serum starvation was carried out in Dulbecco’s modified Eagle’s medium for 20 h. Drugs used were as follows unless otherwise indicated: insulin (20 μg/ml; 30 min; #12585-014, Invitrogen), insulin like growth factor 1 (250 ng/ml; 30 min; #PMG0075, Invitrogen), torin 1 (200 nM; 30 min; #S2827, Selleck), torkinib (100 nM; 30 min; #HY-10474, MedChemExpress), pictilisib (1 μM; 2 h; #11600, Cayman Chemical), rapamycin (20 ng/ml; 30 min; #HY-10219, MedChemExpress), Calyculin A (100 nM; 15 min; # 9902, Cell Signaling Technology), okadaic acid (1 μM; 1 h; #5934, Cell Signaling Technology), tautomycetin (1 μM; 1 h; #B7009, APEBIO), BLM (30 μg/ml; 6 h; #S1214, Selleck), etoposide (1 μM; 24 h; #S1225, Selleck), prexasertib (100 nM; 6 h; #S6385, Selleck), AZD7648 (1 μM; 6 h; #S8843, Selleck), AZD5363 (10 μM; 4 h; #S8019, Selleck).