GLUT4-IN-2

GLUT4-IN-2 is a potent and selective GLUT4 inhibitor with IC50s of 11.4 µM and 6.8 µM for GLUT1 and GLUT4, respectively. GLUT4-IN-2 induces cell apoptosis and cell cycle arrest at G0/G1phase. GLUT4-IN-2 shows potent antitumor activity[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

GLUT1:11.4 μM (IC50)

GLUT4:6.8 μM (IC50)

GLUT4-IN-2 (compound F18) induces cell apoptosis and ell cycle arrest at G0/G1phase in CME cells[1]. GLUT4-IN-2 (10 µM; 6 h) decreases the expression of mTOR and CDK2, but increases the expression of GRP78, and cleaved caspase 3 proteins [1]. Cell Viability Assay[1] Cell Line: CME, K562, KCL-22, MB-231, HS-27 cells Concentration: 1-100 µM Incubation Time: 48 h Result: Showed potent cytotoxicity with cytotoxic concentration 50% (CC50) of 1.7, 91.9, 15.3, 45.1, 44.0 µM for CME, K562, KCL-22, MB-231, HS-27 cells, respectively. Apoptosis Analysis[1] Cell Line: CEM cells Concentration: 1.7 µM Incubation Time: 24 h Result: Induced cell apoptosis with the percentage of apoptotic cells in the late and early apoptosis region was 55.87% and 1.38%, respectively. Cell Cycle Analysis[1] Cell Line: CEM cells Concentration: 10, 25, 50 µM Incubation Time: 72 h Result: Induced cell cycle arrest at G0/G1phase in a dose-dependent manner. Western Blot Analysis[1] Cell Line: CEM cells Concentration: 10 µM Incubation Time: 6 h Result: Decreased the phosphorylation of mTOR and CDK2 proteins and increased the expression of GRP78, and cleaved caspase 3. Cell Cytotoxicity Assay[1] Cell Line: CEM cells Concentration: 2.5-100 µM Incubation Time: 48 h Result: Showed cytotoxicity with the IC50s of 1.7, 187.2 µM for CEM, WBCs cells respectively.

GLUT4-IN-2 (50 mg/kg; i.p. on day 1–5, 8–12, 15–18) shows antitumor activity in CEM xenograft model[1]. Animal Model: 8–10 weeks, SCID mice (CEM xenograft tumor) [1] Dosage: 50 mg/kg Administration: I.p.; administered on day 1-5, 8-12, 15-18 Result: Showed potent antitumor activity in vivo.

[1]. Tilekar K,et al. Structure guided design and synthesis of furyl thiazolidinedione derivatives as inhibitors of GLUT 1 and GLUT 4, and evaluation of their anti-leukemic potential. Eur J Med Chem. 2020 Sep 15;202:112603.