GSK-A1

• CAT Number: I028424
• CAS Number: 1416334-69-4
• Molecular Formula: C29H27FN6O4S
• Molecular Weight: 574.63
• Purity: ≥95%
• Synonyms: 5-[2-amino-3-(4-morpholin-4-ylphenyl)benzimidazol-5-yl]-N-(2-fluorophenyl)-2-methoxypyridine-3-sulfonamide
• InChI: InChI=1S/C29H27FN6O4S/c1-39-28-27(41(37,38)34-24-5-3-2-4-23(24)30)17-20(18-32-28)19-6-11-25-26(16-19)36(29(31)33-25)22-9-7-21(8-10-22)35-12-14-40-15-13-35/h2-11,16-18,34H,12-15H2,1H3,(H2,31,33)
• InChIKey: AJOGHKUZDLYXKS-UHFFFAOYSA-N
• SMILES: COC1=C(C=C(C=N1)C2=CC3=C(C=C2)N=C(N3C4=CC=C(C=C4)N5CCOCC5)N)S(=O)(=O)NC6=CC=CC=C6F

GSK-A1 is a selective type III phosphatidylinositol 4-kinase PI4KA (PI4KIIIα) inhibitor with a pIC50 of 8.5-9.8. GSK-A1 inhibits PtdIns(4,5)P2 resynthesis with an IC50 of about 3 nM. GSK-A1 potently decreases the levels of PtdIns(4)P with a negligible effect on PtdIns(4,5)P2. GSK-A1 has the potential for anti-hepatitis C virus (HCV) research[1].
GSK-A1 (100 nM, 30 min) reduces HSPA1A localization at the plasma membrane in HeLa cells[2].
GSK-A1 (0-8 μM, 48 h) enhances Doxorubicin (HY-15142A) efficacy in resistant leukemia cells (K562/Adr and HL-60/Adr cells)[3].
GSK-A1 (0-50 nM) stimulates phosphorylation of LATS and YAP in HEK293A cells[4].

Reference

[1]. Naveen Bojjireddy, et al.  Pharmacological and genetic targeting of the PI4KA enzyme reveals its important role in maintaining plasma membrane phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate levels. J Biol Chem. 2014 Feb 28;289(9):6120-32.
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[2]. Smulders L, et al. Phosphatidylinositol Monophosphates Regulate the Membrane Localization of HSPA1A, a Stress-Inducible 70-kDa Heat Shock Protein. Biomolecules. 2022 Jun 20;12(6):856.
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[3]. Jiang X, et al. Targeting PI4KA sensitizes refractory leukemia to chemotherapy by modulating the ERK/AMPK/OXPHOS axis. Theranostics. 2022 Oct 3;12(16):6972-6988.
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[4]. Li FL, et al. Hippo pathway regulation by phosphatidylinositol transfer protein and phosphoinositides. Nat Chem Biol. 2022 Oct;18(10):1076-1086.
 [Content Brief]