retinoblastoma

BS194 is as a potent cyclin-dependent protein kinases (CDKs) inhibitor.

KDM5-C70 is an ethyl ester derivative of KDM5-C49 and functions as an effective, cell-permeable, pan-KDM5 histone demethylase inhibitor. It exhibits an antiproliferative effect in myeloma cells and induces a genome-wide elevation of H3K4me3 levels.

Amsilarotene (TAC101) inhibits the phosphorylation of retinoblastoma gene product (RB) and increases the presence of 2 cyclin-dependent kinases (CDK) inhibitors resulting in cell cycle arrest. This agent also causes a cytotoxic decline in the thymidylate synthase and cyclin A expression.

A-83586C is a depsipeptide antibiotic from Streptomyces karnatakensis with potent against Gram-positive activity in vitro. A-83586C acts as a highly potent inhibitor of beta-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating o

BMS-665053 is a corticotropin-releasing factor-1 (CRF1) receptor antagonist (IC50 = 1.0 nM) that inhibits CRF-stimulated cyclic adenosine monophosphate (cAMP) production in human Y-79 retinoblastoma cells (IC50 = 4.9 nM). It is also efficacious in the Defensive Withdrawal model of anxiety in rats and has low in vivo clearance [Cl = 17 mL min kg, t½ = 7.8 h].

Perivine (Perivin) may resolve the instability of the retinoblastoma-associated proteins (RbAp48) complex and thus be used in Alzheimer's disease therapy. Perivine, vobasine, coronaridine and dichomine show hypotensive and muscle relaxant activity.

CDK-IN-9 (compound 24) is a potent inhibitor of CDK and acts on CDK2 E (IC50: 4 nM). It functions as a molecular gel that induces interaction between CDK12 and DDB1, and can dephosphorylate retinoblastoma protein and RNA polymerase II, thereby inducing apoptosis.

AG-012986 is a multitargeted cyclin-dependent kinase (CDK) inhibitor active against CDK1, CDK2, CDK4 6, CDK5, and CDK9, with selectivity over a diverse panel of non-CDK kinases. AG-012986 showed antiproliferative activities in vitro with IC(50)s of <100 nmol L in 14 of 18 tumor cell lines. In vivo, significant antitumor efficacy induced by AG-012986 was seen (tumor growth inhibition, >83.1%) in 10 of 11 human xenograft tumor models. AG-012986 also showed dose-dependent retinoblastoma Ser(795) hypophosphorylation, cell cycle arrest, decreased Ki-67 tumor staining, and apoptosis in conjunction with antitumor activity.

AG-012986 HCl is a multitargeted cyclin-dependent kinase (CDK) inhibitor active against CDK1, CDK2, CDK4 6, CDK5, and CDK9, with selectivity over a diverse panel of non-CDK kinases. AG-012986 HCl showed antiproliferative activities in vitro with IC(50)s of <100 nmol L in 14 of 18 tumor cell lines. In vivo, significant antitumor efficacy induced by AG-012986 HCl was seen (tumor growth inhibition, >83.1%) in 10 of 11 human xenograft tumor models. AG-012986 HCl also showed dose-dependent retinoblastoma Ser(795) hypophosphorylation, cell cycle arrest, decreased Ki-67 tumor staining, and apoptosis in conjunction with antitumor activity.

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

BAY 61-3606 HCl is a cell-permeable, reversible inhibitor of spleen tyrosine kinase. BAY 61-3606 HCl can inhibit degranulation and block cytokine release from mast cells. Oral administration of BAY 61-3606 to rats was shown to suppress antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema. It can also sensitize MCF-7 breast cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by inhibiting Cdk9. This compound has been used in a pre-clinical model to explore the feasibility of targeting Syk in the treatment of retinoblastoma.

D-erythro-Sphingosine hydrochloride, also known as Erythrosphingosine, serves as a specific TRPM3 activator and induces retinoblastoma protein dephosphorylation.

CDK4 6-IN-15, an orally active and selective inhibitor of CDK4 6, effectively halts the growth of cancer cells by arresting the cell cycle at the G1 phase and inhibiting the phosphorylation of the retinoblastoma tumor suppressor protein (Rb) at S780, as well as suppressing E2 factor (E2F)-regulated gene expression.

TPCK is an irreversible inhibitor of chymotrypsin-like proteases that affect cell proliferation, apoptosis, and tumorigenesis

PAWI-2 functions as both a p53 activator and a Wnt inhibitor. It suppresses β3-KRAS signaling independently of KRAS and selectively inhibits the phosphorylation of TBK1. Additionally, PAWI-2 triggers apoptosis (activation of caspase-3 7) and induces PARP cleavage. It facilitates the translocation of retinoblastoma protein into the nucleus, leading to G2 M cell cycle arrest. PAWI-2 reverses the cancer stem cell-like properties of KRAS-dependent human pancreatic cancer stem cells (hPCSC) and overcomes drug resistance. Moreover, it inhibits the growth of hPCSC tumors in an orthotopic xenograft mouse model.

Dalpiciclib (SHR-6390) is a highly selective, orally bioavailable, and comparable potency inhibitor of CDK4 and CKD6 with IC50s of 12.4 nM and 9.9 nM, respectively. Dalpiciclib exerts potent antitumor activity in esophageal squamous cell carcinoma by inhibiting phosphorylated tumor suppressor retinoblastoma protein (Rb) and inducing G1 cell cycle arrest.