SYUIQ-5 is a G-quadruplex stabilizer. SYUIQ-5 stabilizes the c-myc promoter G-quadruplex, the VEGF promoter G-quadruplex, and the telomeric G-quadruplex. SYUIQ-5 selectively inhibits telomerase but not Taq polymerase, while decreasing c-myc / hTERT expression and dissociating NM23-H2. SYUIQ-5 induces growth arrest, senescence, autophagy, DNA damage response, telomere shortening, and apoptosis, accompanied by upregulation of p16 / p21 / p27, decreased TRF2, and pro-catabolic myotube changes. SYUIQ-5 can be used for research on leukemia, colon cancer, cervical cancer, nasopharyngeal carcinoma, Burkitt lymphoma, and sarcopenia [1] [2] [3] [4] [5] [6] [7].
In Vitro, SYUIQ-5 (0.6-10 mg/mL) dose-dependently inhibits cell-free PCR product formation from the c-myc promoter Pu22myc G-quadruplex-forming oligomer, while the mutant Pu22mu control is not inhibited[1]. SYUIQ-5 (0.4-1.0 µM; 72 h) increases SA-β-galactosidase activity in C2C12 myoblasts[7]. SYUIQ-5 (0.4-1.0 μg/mL for HL-60; 0.4-1.2 μg/mL for K562; 72 h) inhibits c-myc mRNA and protein expression in HL-60 and K562 leukemia cells[1]. SYUIQ-5 (0.4-1.0 μg/mL; 72 h) dose-dependently inhibits E2F1 and hTERT and decreases TRF2, with only a slight decrease in TRF1 in HL-60 cells[1]. SYUIQ-5 (3 days) inhibits telomerase activity in HL-60 cells, with reported inhibition of 22.6-64.2%[1]. SYUIQ-5 (3 days) has an IC50 of 1.6 mg/mL in a cytotoxic assay against HL-60 cells[1]. SYUIQ-5 (0.05-0.8 μM; 30 min) is a potent cell-free telomerase inhibitor in K562 extract, with an IC50 of 0.44 μM[2]. SYUIQ-5 (0.15-0.6 μM; 72 h) inhibits telomerase activity in K562 and SW620 cells, with 0.6 μM producing 84.1% and 79.5% inhibition, respectively[2]. SYUIQ-5 (3 days) has MTT IC50 values of 2.65 μM in K562 cells and 1.68 μM in SW620 cells[2]. SYUIQ-5 (0.1-0.4 μM; 16-35 days) induces growth arrest and senescence-associated β-galactosidase in K562 and SW620 cells under continuous nonacute exposure[2]. SYUIQ-5 (0.2-0.4 μM; long-term exposure) shortens telomeres by about 6.1 kbp in K562 cells and about 2.5 kbp in SW620 cells[2]. SYUIQ-5 (0.1-0.4 μM; 3 days) decreases hTERT protein expression in K562 and SW620 cells[2]. SYUIQ-5 (0.5508-0.9322 μg/mL; 72 h) inhibits proliferation of CNE2 and HeLa cancer cells with IC50 values of 0.9322 and 0.5508 μg/mL, respectively[3]. SYUIQ-5 (0.5-4 μg/mL; 24-48 h) induces telomere DNA damage with γ-H2AX foci that colocalize with TRF1 in CNE2 and HeLa cells[3]. SYUIQ-5 (0.1 μM; 4 days) down-regulates c-myc and hTERT transcription in Ramos lymphoma cells but not in CA46 cells[6]. SYUIQ-5 (0.05-0.1 μM; 4 days) inhibits c-Myc and hTERT protein expression in Ramos cells and c-Myc expression in CA46 cells[6]. SYUIQ-5 (0.1 μM; 4 days) interferes with NM23-H2 binding to the c-myc promoter but not with POT-1 binding to telomeric ssDNA in HeLa S3 cells[6]. SYUIQ-5 (0.1 μM; 24 h) dissociates NM23-H2 from the wild-type c-myc promoter but not from a mutant promoter in HeLa cells[6]. SYUIQ-5 (0.05-0.1 μM; 16 days) shortens telomeres more strongly in Ramos cells (~1.6 kb) than in CA46 cells (0.8 kb)[6]. SYUIQ-5 (0.05-0.1 μM; 16 days) induces senescence in Ramos cells but has no obvious effect in CA46 cells[6]. SYUIQ-5 inhibits proliferation of diverse tumor cell lines with IC50 values of 0.24-4.8 μM[6]. SYUIQ-5 (0.4-2.0 µM; 72 h) did not exert toxic effects on C2C12 myoblasts below 2 µM, whereas 2 µM was toxic after 72 h[7]. SYUIQ-5 (0.4-1.0 µM; 72 h) activates DNA damage response in C2C12 myoblasts, increasing γ-H2AX and phosphorylated p53[7]. SYUIQ-5 (0.4 mg/mL; 6-12 days) upregulates P16, P21, and P27 in HL-60 cells, associating with growth arrest[1]. SYUIQ-5 (0.05-0.4 μM; 18-35 days) upregulates p16, p21 and p27 in K562 and SW620 cells[2]. SYUIQ-5 (0.4 mg/mL; 9 days) induces delayed apoptosis in HL-60 cells, with caspase-3 and PARP cleavage and sub-G1 accumulation[1]. SYUIQ-5 (0.5-4 μg/mL; 24-48 h) induces autophagy in CNE2 and HeLa cancer cells, increasing LC3-II, MDC-labeled autophagosomes, and YFP-LC3 puncta[3]. SYUIQ-5 (4 μg/mL for 24 h; 0.5-4 μg/mL for 48 h)-mediated telomere DNA damage, autophagy, and cell death in CNE2 and HeLa cells is antagonized by overexpression of wild-type TRF2[3]. SYUIQ-5 (4 μg/mL) induces telomere DNA damage and autophagy in an ATM-dependent manner in CNE2 and HeLa cells[3]. SYUIQ-5 (2 μg/mL for 24 h; various concentrations for 72 h) induces autophagy and cytotoxicity in CNE2 and HeLa cells that is attenuated by ATG5 knockdown, indicating autophagic cell death[3]. SYUIQ-5 (0.5-4 μg/mL; 24-48 h) delocalizes TRF2 from telomeres and promotes its proteasomal degradation in CNE2 and HeLa cells, while TRF1 remains telomere-bound[3]. SYUIQ-5 (0.4-1.0 µM; 72 h) reduces C2C12 myoblast proliferation and increases p21 expression at 1 µM[7].
References:
[1]. Liu JN, et al. Inhibition of myc promoter and telomerase activity and induction of delayed apoptosis by SYUIQ-5, a novel G-quadruplex interactive agent in leukemia cells. Leukemia. 2007 Jun;21(6):1300-2.
[2]. Zhou JM, et al. Senescence and telomere shortening induced by novel potent G-quadruplex interactive agents, quindoline derivatives, in human cancer cell lines. Oncogene. 2006 Jan 26;25(4):503-11.
[3]. Zhou WJ, et al. G-quadruplex ligand SYUIQ-5 induces autophagy by telomere damage and TRF2 delocalization in cancer cells. Molecular cancer therapeutics. 2009 Dec;8(12):3203-13.
[4]. Wu Y, et al. Stabilization of VEGF G-quadruplex and inhibition of angiogenesis by quindoline derivatives. Biochimica et biophysica acta. 2014 Sep;1840(9):2970-7.
[5]. Liu HY, et al. New Disubstituted Quindoline Derivatives Inhibiting Burkitt's Lymphoma Cell Proliferation by Impeding c-MYC Transcription. Journal of medicinal chemistry. 2017 Jul 13;60(13):5438-5454.
[6]. Ou TM, et al. Inhibition of cell proliferation by quindoline derivative (SYUIQ-05) through its preferential interaction with c-myc promoter G-quadruplex. Journal of medicinal chemistry. 2011 Aug 25;54(16):5671-9.
[7]. Gerosa L, et al. Murine Myoblasts Exposed to SYUIQ-5 Acquire Senescence Phenotype and Differentiate into Sarcopenic-Like Myotubes, an In Vitro Study. The journals of gerontology. Series A, Biological sciences and medical sciences. 2024 Apr 01;79(4):glae022.
In Vitro, SYUIQ-5 (0.6-10 mg/mL) dose-dependently inhibits cell-free PCR product formation from the c-myc promoter Pu22myc G-quadruplex-forming oligomer, while the mutant Pu22mu control is not inhibited[1]. SYUIQ-5 (0.4-1.0 µM; 72 h) increases SA-β-galactosidase activity in C2C12 myoblasts[7]. SYUIQ-5 (0.4-1.0 μg/mL for HL-60; 0.4-1.2 μg/mL for K562; 72 h) inhibits c-myc mRNA and protein expression in HL-60 and K562 leukemia cells[1]. SYUIQ-5 (0.4-1.0 μg/mL; 72 h) dose-dependently inhibits E2F1 and hTERT and decreases TRF2, with only a slight decrease in TRF1 in HL-60 cells[1]. SYUIQ-5 (3 days) inhibits telomerase activity in HL-60 cells, with reported inhibition of 22.6-64.2%[1]. SYUIQ-5 (3 days) has an IC50 of 1.6 mg/mL in a cytotoxic assay against HL-60 cells[1]. SYUIQ-5 (0.05-0.8 μM; 30 min) is a potent cell-free telomerase inhibitor in K562 extract, with an IC50 of 0.44 μM[2]. SYUIQ-5 (0.15-0.6 μM; 72 h) inhibits telomerase activity in K562 and SW620 cells, with 0.6 μM producing 84.1% and 79.5% inhibition, respectively[2]. SYUIQ-5 (3 days) has MTT IC50 values of 2.65 μM in K562 cells and 1.68 μM in SW620 cells[2]. SYUIQ-5 (0.1-0.4 μM; 16-35 days) induces growth arrest and senescence-associated β-galactosidase in K562 and SW620 cells under continuous nonacute exposure[2]. SYUIQ-5 (0.2-0.4 μM; long-term exposure) shortens telomeres by about 6.1 kbp in K562 cells and about 2.5 kbp in SW620 cells[2]. SYUIQ-5 (0.1-0.4 μM; 3 days) decreases hTERT protein expression in K562 and SW620 cells[2]. SYUIQ-5 (0.5508-0.9322 μg/mL; 72 h) inhibits proliferation of CNE2 and HeLa cancer cells with IC50 values of 0.9322 and 0.5508 μg/mL, respectively[3]. SYUIQ-5 (0.5-4 μg/mL; 24-48 h) induces telomere DNA damage with γ-H2AX foci that colocalize with TRF1 in CNE2 and HeLa cells[3]. SYUIQ-5 (0.1 μM; 4 days) down-regulates c-myc and hTERT transcription in Ramos lymphoma cells but not in CA46 cells[6]. SYUIQ-5 (0.05-0.1 μM; 4 days) inhibits c-Myc and hTERT protein expression in Ramos cells and c-Myc expression in CA46 cells[6]. SYUIQ-5 (0.1 μM; 4 days) interferes with NM23-H2 binding to the c-myc promoter but not with POT-1 binding to telomeric ssDNA in HeLa S3 cells[6]. SYUIQ-5 (0.1 μM; 24 h) dissociates NM23-H2 from the wild-type c-myc promoter but not from a mutant promoter in HeLa cells[6]. SYUIQ-5 (0.05-0.1 μM; 16 days) shortens telomeres more strongly in Ramos cells (~1.6 kb) than in CA46 cells (0.8 kb)[6]. SYUIQ-5 (0.05-0.1 μM; 16 days) induces senescence in Ramos cells but has no obvious effect in CA46 cells[6]. SYUIQ-5 inhibits proliferation of diverse tumor cell lines with IC50 values of 0.24-4.8 μM[6]. SYUIQ-5 (0.4-2.0 µM; 72 h) did not exert toxic effects on C2C12 myoblasts below 2 µM, whereas 2 µM was toxic after 72 h[7]. SYUIQ-5 (0.4-1.0 µM; 72 h) activates DNA damage response in C2C12 myoblasts, increasing γ-H2AX and phosphorylated p53[7]. SYUIQ-5 (0.4 mg/mL; 6-12 days) upregulates P16, P21, and P27 in HL-60 cells, associating with growth arrest[1]. SYUIQ-5 (0.05-0.4 μM; 18-35 days) upregulates p16, p21 and p27 in K562 and SW620 cells[2]. SYUIQ-5 (0.4 mg/mL; 9 days) induces delayed apoptosis in HL-60 cells, with caspase-3 and PARP cleavage and sub-G1 accumulation[1]. SYUIQ-5 (0.5-4 μg/mL; 24-48 h) induces autophagy in CNE2 and HeLa cancer cells, increasing LC3-II, MDC-labeled autophagosomes, and YFP-LC3 puncta[3]. SYUIQ-5 (4 μg/mL for 24 h; 0.5-4 μg/mL for 48 h)-mediated telomere DNA damage, autophagy, and cell death in CNE2 and HeLa cells is antagonized by overexpression of wild-type TRF2[3]. SYUIQ-5 (4 μg/mL) induces telomere DNA damage and autophagy in an ATM-dependent manner in CNE2 and HeLa cells[3]. SYUIQ-5 (2 μg/mL for 24 h; various concentrations for 72 h) induces autophagy and cytotoxicity in CNE2 and HeLa cells that is attenuated by ATG5 knockdown, indicating autophagic cell death[3]. SYUIQ-5 (0.5-4 μg/mL; 24-48 h) delocalizes TRF2 from telomeres and promotes its proteasomal degradation in CNE2 and HeLa cells, while TRF1 remains telomere-bound[3]. SYUIQ-5 (0.4-1.0 µM; 72 h) reduces C2C12 myoblast proliferation and increases p21 expression at 1 µM[7].
References:
[1]. Liu JN, et al. Inhibition of myc promoter and telomerase activity and induction of delayed apoptosis by SYUIQ-5, a novel G-quadruplex interactive agent in leukemia cells. Leukemia. 2007 Jun;21(6):1300-2.
[2]. Zhou JM, et al. Senescence and telomere shortening induced by novel potent G-quadruplex interactive agents, quindoline derivatives, in human cancer cell lines. Oncogene. 2006 Jan 26;25(4):503-11.
[3]. Zhou WJ, et al. G-quadruplex ligand SYUIQ-5 induces autophagy by telomere damage and TRF2 delocalization in cancer cells. Molecular cancer therapeutics. 2009 Dec;8(12):3203-13.
[4]. Wu Y, et al. Stabilization of VEGF G-quadruplex and inhibition of angiogenesis by quindoline derivatives. Biochimica et biophysica acta. 2014 Sep;1840(9):2970-7.
[5]. Liu HY, et al. New Disubstituted Quindoline Derivatives Inhibiting Burkitt's Lymphoma Cell Proliferation by Impeding c-MYC Transcription. Journal of medicinal chemistry. 2017 Jul 13;60(13):5438-5454.
[6]. Ou TM, et al. Inhibition of cell proliferation by quindoline derivative (SYUIQ-05) through its preferential interaction with c-myc promoter G-quadruplex. Journal of medicinal chemistry. 2011 Aug 25;54(16):5671-9.
[7]. Gerosa L, et al. Murine Myoblasts Exposed to SYUIQ-5 Acquire Senescence Phenotype and Differentiate into Sarcopenic-Like Myotubes, an In Vitro Study. The journals of gerontology. Series A, Biological sciences and medical sciences. 2024 Apr 01;79(4):glae022.