s phase

Stattic (STAT3 Inhibitor V) is a STAT3 inhibitor (IC50=5.1 μM) that selectively inhibits STAT3 activation, dimerization, and nuclear translocation. Stattic has antitumor activity and induces apoptosis.

1. Citric acid (Citro) (1-2 g kg) can decrease brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation. 2. Citric acid denture cleansers can reduce C. albicans biofilm accumulation and cell viability. However, this CT did not prevent biofilm recolonization.

DI-87 (TRE-515) is a novel and orally available dCK (deoxycytidine kinase) inhibitor with good in vitro activity and low protein binding. DI-87 binds to dCK and prevents the phosphorylation of deoxycytidine by dCK, which reduces the production of dNTP and cell cycle arrest (especially in S phase). When combined with thymidine, DI-87 significantly inhibits tumor growth.

TJ08 is a 1,2,5-trisubstituted benzimidazole derivative with anticancer properties that effectively induces G1 S phase blockade while promoting apoptotic effects in a variety of cancer cells.

Sophoridine (Dihydro-5-episophocarpine), a natural anticancer drug, has been used in China for decades. A series of novel N-substituted Sophoridinic acid derivatives were synthesized and evaluated for their cytotoxicity with 1 as the lead. The structure-activity relationship indicated that introduction of an aliphatic acyl on the nitrogen atom might significantly enhance the anticancer activity. Among the compounds, 6b bearing bromoacetyl side-chain afforded a potential effect against four human tumor cell lines (liver, colon, breast, and lung). The mechanism of action of 6b is to inhibit the activity of DNA topoisomerase I, followed by the S-phase arrest and then cause apoptotic cell death, similar to that of its parent 1.

Citric Acid Monohydrate is a tricarboxylic acid found in citrus fruits. Citric acid is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It maintains stability of active ingredients and is used as a preservative.

Sodium citrate (Natrocitral) is the sodium salt of citric acid.Citric acid trisodium induces apoptosis and cell cycle arrest at G2 M phase and S phase. Sodium citrate cause oxidative damage of the liver by means of the decrease of antioxidative enzyme activities.

Oltipraz (RP 35972) is a synthetic dithiolethione with potential chemopreventive and anti-angiogenic properties. Oltipraz induces phase II detoxification enzymes, such as glutathione S transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). The induction of detoxification enzymes enhances the detoxification of certain cancer-causing agents, thereby enhancing their elimination and preventing carcinogen-induced DNA damages. Although the exact mechanism through which the anti-angiogenesis effect remains to be fully elucidated, oltipraz maybe able to modulate the expression of a number of angiogenic factors, thereby blocking the sustained and focal neovascularization in multiple tumor cell types.

Thymidine (DThyd) is a cell synchronizing agent and a specific precursor of deoxyribonucleic acid. Thymidine inhibits DNA synthesis and can cause cell cycle arrest in the G1 S phase.

Cytarabine hydrochloride (Ara-C hydrochloride) is a nucleoside analog that causes S phase cell cycle arrest and inhibits DNA polymerase. Cytarabine inhibits DNA synthesis with an IC 50 of 16 nM. Cytarabine hydrochloride has antiviral effects against HSV.

S-trityl-L-Cysteine is a non-natural amino acid and an inhibitor of Eg5, also known as KSP and Kif11, a mitotic kinesin necessary for mitotic spindle formation. S-trityl-L-Cysteine inhibits the ATPase activity of Eg5 in basal and microtubule-stimulated states (IC50s = 1,000 and 140 nM, respectively). It is selective for Eg5 over nine other human kinesins in an enzyme-coupled assay. It reversibly inhibits Eg5-driven microtubule sliding velocity with an IC50 value of 500 nM using X. laevis recombinant Eg5. It induces cell cycle arrest in HeLa cells (IC50 = 700 nM), reversibly halting the cell cycle in the mitotic phase by inhibiting the separation of duplicated chromosomes and preventing bipolar spindle formation. S-trityl-L-Cysteine inhibits the growth of cancer cells in vitro when tested against the National Cancer Institute (NCI) 60 human cancer cell line panel (average GI50 = 1.3 μM) and in mouse xenograft models.

Irinotecan Hydrochloride (CPT-11 hydrochloride) is the hydrochloride salt of a semisynthetic derivative of camptothecin. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Because ongoing DNA synthesis is necessary for irinotecan to exert its cytotoxic effects, it is classified as an S-phase-specific agent.

Ancitabine hydrochloride (NSC 145668 HCl) is the hydrochloride salt of a cytarabine congener prodrug with antineoplastic activity. Upon administration, ancitabine is slowly hydrolyzed into cytarabine. Subsequently, cytarabine is converted to the triphosphate form within the cell and then competes with cytidine for incorporation into DNA. Because the arabinose sugar sterically hinders the rotation of the molecule within DNA, DNA replication ceases, specifically during the S phase of the cell cycle. Cytarabine agent also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair. Compared to cytarabine, a more prolonged, consistent cytarabine-mediated therapeutic effect may be achieved with ancitabine because of the slow hydrolytic conversion of ancitabine to cytarabine.

Icaritin (Anhydroicaritin) has hormone regulation activity and cardiovascular function improvement activity. Icaritin has anticancer activity, can induce S phase arrest and apoptosis, inhibit ENKL cell proliferation. Icaritin has anti-multiple myeloma activity, mainly mediated by inhibiting IL-6 JAK2 STAT3 signaling. Icaritin at low concentration (4 or 8 μMol L) can promote rat chondrocyte proliferation and inhibit cell apoptosis, while the effect of Icaritin on rat chondrocyte at high concentration was reversed.

Indisulam (E 7070) is a carbonic anhydrase inhibitor and antitumor CDK inhibitor that targets the G1 phase of the cell cycle by depleting cyclin E, inducing p53 and p21, and inhibiting CDK2, thereby causing a blockade in the G1 S transition.

CVT-11127 is an StearoylCoA Desaturase-1 (SCD1) inhibitor.

Acetyl Ser-Asp-Lys-Pro is formed in bone marrow cells by enzymatic processing of thymosin β4. It inhibits the entry of pluripotent hemopoietic stem cells into S-phase of the cell cycle and protects against Ara-C lethality in mice.

PROTAC GSPT1 degrader-1 (Compound F) is a PROTAC-based degrader that effectively targets and degrades G1 to S phase transition protein 1 (GSPT1), achieving degradation rates of 95% at 1 μM and 86% at 0.1 μM. Additionally, this compound inhibits the viability of HL-60 cells with an IC50 of 9.2 nM.

CAY10711 is a substituted diamine that produces rapid bactericidal activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant S. aureus (MRSA) and stationary-phase bacteria. It displays MIC99 values of 2.9, 11.5, 2.9, and 2.9 μM against S. aureus RN4220, P. aeruginosa PAO1, E. coli ANS1, and MRSA 10082B, respectively. CAY10711 reduces biofilm formation and promotes biofilm dispersal in P. aeruginosa. It is synergistic with kanamycin and has limited adverse effects against mammalian cells or C. elegans development, survival, or reproduction.

Topoisomerase II inhibitor 18 (Compound IV), a Quinoxaline derivative, exhibits an IC 50 of 7.5 μM in inhibiting topoisomerase II. It impedes PC-3 cell proliferation, arrests the cell cycle at the S phase, and induces apoptosis. Moreover, this compound demonstrates substantial antitumor activity against cancer [1].

TH9619 is an MTHFD2 inhibitor with an IC50 value of 47 nM, inducing apoptosis by blocking the S phase and exhibiting antitumor activity [1].

CAIX-IN-2 (Compound 9o) is an inhibitor of carbonic anhydrase (CA), targeting CAIX, CA XII, and CAII with IC50 values of 5.6, 7.4, and 430 nM, respectively. This compound effectively inhibits the proliferation of cancer cells such as HCT-116, SW480, MDA-MB 231, and MCF-7, with IC50 values ranging from 14.63 to 29.33 µM. CAIX-IN-2 also integrates into DNA, causing cell cycle arrest at the G1 S phase and inducing apoptosis in MDA-MB-231 cells. Furthermore, it disrupts mitochondrial membrane potential (MMP), elevates intracellular ROS levels, leading to mitochondrial damage, and inhibits the migration of MDA-MB-231 cells. In mouse models, CAIX-IN-2 has demonstrated antitumor activity.

(+)-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.

CDK HDAC-IN-4 is a highly selective dual inhibitor of cyclin-dependent kinase (CDK) and histone deacetylase (HDAC), with IC50 values of 88.4 nM and 168.9 nM, respectively. This compound exhibits antiproliferative effects in both hematologic and solid tumor cells. Additionally, CDK HDAC-IN-4 induces apoptosis and S-phase cell cycle arrest in MV-4-11 cells. It has also demonstrated significant antitumor efficacy in an MV-4-11 xenograft model.