GSK-1059615

• CAT Number: I005685
• CAS Number: 958852-01-2
• Molecular Formula: C₁₈H₁₁N₃O₂S
• Molecular Weight: 333.36
• Purity: ≥95%
• Target: PI3K
• Solubility: Soluble to 10 mM in DMSO
• Storage: Store at +4°C
• IC50: 0.4 nM/0.6 nM/2 nM/5 nM(PI3Kα/β/δ/γ); 12 nM (mTOR)
• InChI: InChI=1S/C18H11N3O2S/c22-17-16(24-18(23)21-17)10-11-1-2-15-14(9-11)13(5-8-20-15)12-3-6-19-7-4-12/h1-10H,(H,21,22,23)/b16-10-
• InChIKey: QDITZBLZQQZVEE-YBEGLDIGSA-N
• SMILES: C1=CC2=NC=CC(=C2C=C1C=C3C(=O)NC(=O)S3)C4=CC=NC=C4

GSK-1059615(CAT: I005685) is a dual inhibitor of PI3Kα/β/δ/γ (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin). PI3K and mTOR are both key components of the PI3K/AKT/mTOR signaling pathway, which regulates various cellular processes including cell growth, proliferation, and survival. By inhibiting these enzymes, GSK-1059615 can disrupt the signaling pathway and potentially inhibit the growth and survival of cancer cells. It is being studied as a potential therapeutic agent for various types of cancer.

Reference

1. Oncotarget. 2017 Feb 7;8(31):50814-50823. doi: 10.18632/oncotarget.15135.
eCollection 2017 Aug 1.

GSK1059615 kills head and neck squamous cell carcinoma cells possibly via
activating mitochondrial programmed necrosis pathway.

Xie J(1), Li Q(2), Ding X(1), Gao Y(1).

Author information:
(1)Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical
University, Wenzhou, China.
(2)Center of Stomatology, The Second Affiliated Hospital of Soochow University,
Suzhou, China.

This study tested the anti-head and neck squamous cell carcinoma (HNSCC) cell
activity by GSK1059615, a novel PI3K and mTOR dual inhibitor. GSK1059615
inhibited survival and proliferation of established (SCC-9, SQ20B and A253 lines)
and primary human HNSCC cells. GSK1059615 blocked PI3K-AKT-mTOR activation in
HNSCC cells. Intriguingly, GSK1059615 treatment in HNSCC cells failed to provoke
apoptosis, but induced programmed necrosis. The latter was tested by mitochondria
depolarization, ANT-1-cyclophilin-D mitochondrial association and lactate
dehydrogenase (LDH) release. Reversely, mPTP blockers (sanglifehrin A,
cyclosporin A and bongkrekic acid) or cyclophilin-D shRNA dramatically alleviated
GSK1059615-induced SCC-9 cell death. Further studies demonstrated that GSK1059615
i.p. injection suppressed SCC-9 tumor growth in nude mice, which was compromised
with co-administration with cyclosporin A. Thus, targeting PI3K-AKT-mTOR pathway
by GSK1059615 possibly provokes programmed necrosis pathway to kill HNSCC cells.