g0/g1

PR-619 (2,6-Diamino-3,5-dithiocyanopyridine) is a DUB inhibitor that inhibits USP2 4 5 7 8 (EC50=7.2 3.93 8.61 6.86 4.9 μM). PR-619 induces endoplasmic reticulum stress and activates autophagy.

Mevastatin (ML236B) is an HMG-CoA reductase inhibitor that was initially isolated from the mold Pythium ultimum. Mevastatin was the first statin to enter clinical trials.

Iberdomide (CC-220) is a modulator of cereblon( IC50 value of 60 nM in a competitive TR-FRET assay).

Ailanthone (AIL) is a natural compound derived from the tree Ailanthus altissima and has anti-hepatocellular carcinoma (HCC) properties. It can induce G0 G1 phase cell cycle arrest by downregulating the expression of cyclins and CDKs, while upregulating the expression of p21 and p27. Additionally, Ailanthone is a potent androgen receptor (AR) inhibitor, capable of inhibiting both the full-length androgen receptor (IC50: 69 nM) and constitutively active splice variants (IC50: 309 nM).

EGFR-IN-11 is a selective inhibitor of EGFR-tyrosine kinase and induces cell apoptosis. EGFR-IN-11 inhibits triple mutant EGFRL858R T790M C797S with an IC50 of 18 nM and arrests cell cycle at G0 G1.

σ1 Receptor antagonist-1 is a selective σ1 receptor antagonist.

HNPMI is an EGFR inhibitor that induces G0 G1 phase arrest of CRC cells in colorectal cancer, regulates enzymes associated with apoptosis, and can promote apoptosis, and can be used for the study of colorectal cancer.

Compound B6, also known as TOPOI PARP-1-IN-1, is a dual inhibitor targeting TOPOI and PARP, exhibiting low cytotoxicity and oral activity with a PARP1 IC 50 of 0.09 μM. This compound effectively inhibits cancer cell proliferation and migration, induces cell cycle arrest at the G0 G1 phase, and triggers apoptosis. In murine models, TOPOI PARP-1-IN-1 demonstrated a tumor growth inhibition rate (TGI) of 75.4% [1].

(+)-Perillyl alcohol (0.25-1 mM) inhibits cell growth in SW480 cells. At a concentration of 1 mM and a duration of 24 hours, (+)-Perillyl alcohol increases the number of cells in the G0 G1 phase and reduces the number in the S phase in SW480 cells.

PROTAC FGFR2 degrader 1 (compound N5) is a potent PROTAC that efficiently targets FGFR2, boasting a DC 50 value of 6.46 nM and an FGFR2 IC 50 of 0.08 nM. This compound exhibits significant anti-proliferative effects and high selectivity. It induces G0 G1 arrest in the cell cycles of KATOIII and SNU16 and inhibits apoptosis by diminishing the activation of p-ERK and p-PLCγ, the downstream proteins of FGFR2. Additionally, PROTAC FGFR2 degrader 1 maintains over 50% inhibition of gastric cancer cells at a concentration of 0.17 nM and effectively suppresses the growth of SNU16 xenograft tumors in a mouse model.

Sampangine, an alkaloid, induces apoptosis by causing cell cycle arrest at the G0 G1 phase and inhibits the biosynthesis of heme.

PROTAC EZH2 Degrader-3 (compound ZJ-20) is a potent EZH2 degrader that exhibits strong inhibitory effects not only on EZH2 protein expression but also on the levels of other PRC2 subunits and H3k27me3 protein. Additionally, PROTAC EZH2 Degrader-3 demonstrates antiproliferative activity by blocking the cell cycle at the G0-G1 phase and inducing apoptosis (cell death). At a concentration of 5 μM and over a period of 24 hours, it effectively suppresses the expression of these critical proteins involved in cell regulation and growth.

Apoptosisinducer 30 (Compound 15a) acts as an anticancer agent. It induces apoptosis in MCF-7 cells through the mitochondrial pathway. This compound elevates intracellular levels of reactive oxygen species (ROS), decreases mitochondrial membrane potential, and arrests the cell cycle at the G0 G1 phase. Apoptosisinducer 30 inhibits cell growth, with an IC50 value of 0.32 μM against MCF-7 cells, and suppresses tumor growth in a mouse breast cancer model.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

BET-IN-20 (compound 10), a BRD4 BD1 inhibitor (IC 50 =1.9 nM), exhibits significant anticancer properties. It promotes apoptosis in acute myeloid leukemia (AML) cells and arrests the cell cycle in the G0 G1 phase. Additionally, BET-IN-20 inhibits both c-Myc and CDK6, and enhances PARP cleavage [1].

Physachenolide C, a selective BET inhibitor, induces apoptosis and arrests the cell cycle at the G0-G1 phase, exhibiting antitumor activity [1].

Topoisomerase IIα-IN-3 is a DNA-inserting topoisomerase-Iiα inhibitor that blocks the cell cycle in G0 G1 phase and induces apoptosis.

HSP90-IN-23 (Comp 12-1), a heat shock protein 90 (HSP90) inhibitor, exhibits potent activity with an IC50 of 9 nM, promotes apoptosis in tumor cells, and arrests their cell cycle at the G0 G1 phase, making it applicable for cancer research [1].

USP7-IN-9, a potent inhibitor of ubiquitin-specific protease 7 (USP7) with an IC50 of 40.8 nM, effectively induces apoptosis and arrests cell progression at the G0 G1 and S phases in RS4;11 cells. It decreases the protein levels of oncoproteins MDM2 and DNMT1 while enhancing the levels of tumor suppressors p53 and p21.

Compound G-5b, an estrogen receptor modulator 10, functions as an estrogen receptor (ER) antagonist (IC50=6.7 nM) and degrader (DC50=0.4 nM). It has the capability to induce apoptosis and block cells at the G1 G0 phase, making it applicable in cancer research [1].

Anticancer agent 70 (Compound 21) is a potent anticancer compound that demonstrates remarkable cytotoxicity against multiple human cancer cell lines. It induces G0 G1-cell cycle arrest and concurrently elevates the levels of p53 and p21 proteins. Furthermore, Anticancer agent 70 induces ATP depletion and disruption of the mitochondrial membrane potential [1].

Anticancer agent 54 is an effective anticancer agent whose anticancer activity depends on DNA embedding and ROS generation. Anticancer agent 54 has an anti-proliferative effect by blocking the cell cycle in G0 G1 phase and inducing apoptosis.

YS-363 is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor (EGFR), with half-maximal inhibitory concentrations (IC50) of 0.96 nM for the wild-type EGFR and 0.67 nM for the L858R mutant variant. It induces G0 G1 cell cycle arrest and apoptosis in targeted cells [1].

GP130-IN-1 (compound 49) is an effective inhibitor of GP130, demonstrating significant in vitro anti-tumor activity and higher selectivity compared to Bazedoxifene. It induces ultrastructural changes in cells, leading to a time-dependent arrest of the cell cycle at the G0 G1 phase, and triggers both apoptosis and autophagy. GP130-IN-1 is useful for research on triple-negative breast cancer.