CDK Inhibitor

DIF-3 is an orally active anticancer agent. DIF-3 reduces the expression levels of cyclin D1 and c-Myc by facilitating their degradation via activation of GSK-3β. DIF-3 inhibits Wnt/β-catenin signaling pathway-related proteins in cells. DIF-3 induces reactive oxygen species (ROS) and autophagy. DIF suppresses the growth of Trypanosoma. cruzi in HT1080 cells. DIF-3 exerts antitumor effects both in vitro and in vivo.

PF 477736 (PF 00477736) is a potent, selective and ATP-competitive inhibitor of Chk1, with a K_i of 0.49 nM, it is also a Chk2 inhibitor, with a K_i of 47 nM. PF 477736 shows <100-fold selectivity for Chk1 over VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3, and Ret (IC₅₀=8 (K_i), 10, 14, 23, 23, 25, and 39 nM, respectively). PF 477736 can enhance Gemcitabine antitumor activity in vitro and in vivo.

XY028-140 is a PROTAC-type degrader targeting CDK4/6, which degrades CDK4/6 by recruiting CRBN-type E3 ligase. XY028-140 can be used in CDK4/6-mediated cancer-related research.

Purvalanol A is a potent CDK inhibitor, which inhibits cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, cdk4-cyclin D1, and cdk5-p35 with IC₅₀s of 4, 70, 35, 850, 75 nM, resepctively.

Borrelidin (Treponemycin) is a bacterial and eukaryal threonyl-tRNA synthetase inhibitor which is a nitrile-containing macrolide antibiotic isolated from Streptomyces rochei. Borrelidin is an inhibitor of Cdc28/Cln2 of the budding yeast, with an IC₅₀ of 24 μM. Borrelidin is a potent angiogenesis inhibitor, with an IC₅₀ of 0.8 nM. Borrelidin induces apoptosis in the tube-forming cells. Borrelidin has strong antimalarial activities, with IC₅₀s of 1.9 nM and 1.8 nM against K1 and FCR3 strains of Plasmodium falciparum, respectively.

BMS-265246 is a potent and selective cyclin-dependent kinase CDK1 and CDK2 inhibitor, with IC₅₀ values of 6 and 9 nM, respectively. BMS-265246 inhibits CHI3L1 (chitinase 3-like-1) stimulation of ACE2 (angiotensin converting enzyme 2) and SPP (viral spike protein priming proteases). BMS-265246 can be used for ovarian cancer and COVID-19 research.

KB-0742 dihydrochloride is a potent, selective and orally active CDK9 inhibitor with an IC₅₀ of 6 nM for CDK9/cyclin T1. KB-0742 dihydrochloride is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 dihydrochloride has potent anti-tumor activity.

Sinigrin (Allyl-glucosinolate) is an orally active glucosinolate found in cruciferous plants. Sinigrin possesses multiple activities such as anti-cancer, antibacterial, antifungal, anti-inflammatory, antioxidant, and inhibition of fat synthesis. Sinigrin can be used in the research of tumors, inflammatory, and metabolic diseases.

FMF-04-159-2 is a covalent CDK14 inhibitor. FMF-04-159-2 inhibits CDK14 and CDK2 with IC₅₀s of 39.6 nM and 256 nM in NanoBRET assay, respectively.

THZ1 Hydrochloride is a selective and potent covalent CDK7 inhibitor with an IC₅₀ of 3.2 nM. THZ1 Hydrochloride also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression.

Dalpiciclib (SHR-6390) hydrochloride is an orally active and highly selective inhibitor of CDK4 and 6 with IC₅₀ values of 12.4 nM and 9.9 nM, respectively. Dalpiciclib hydrochloride shows antitumor activity against breast cancer and esophageal squamous cell carcinoma.

Roniciclib is an orally bioavailable pan-cyclin dependent kinase (CDK) inhibitor, with IC₅₀s of 5-25 nM for CDK1, CDK2, CDK3, CDK4, CDK7 and CDK9.

HQ461 is a molecular glue that promotes CDK12-DDB1 interaction to trigger cyclin K degradation. HQ461-mediated degradation of cyclin K impairs CDK12 function, resulting in decreased CDK12 substrate phosphorylation, downregulation of DNA damage response genes, and cell death.

T025 is an orally active and highly potent inhibitor of Cdc2-like kinase (CLKs), with K_d values of 4.8, 0.096, 6.5, 0.61, 0.074, 1.5 and 32 nM for CLK1, CLK2, CLK3, CLK4, DYRK1A, DYRK1B and DYRK2, respectively. T025 induces caspase-3/7-mediated cell apoptosis. T025 reduces CLK-dependent phosphorylation. T025 exerts anti-proliferative activities in both hematological and solid cancer cell lines (IC₅₀ values: 30-300 nM). T025 has an anti-tumor efficiency, mainly for MYC-driven disease research.

Raddeanin A is an oleanane-type triterpenoid saponin with oral activity. Raddeanin A inhibits SRC, mTOR, JNK, VEGFR2, NLRP3 inflammasome, Wnt/β-catenin, Wee1, PI3K/AKT signaling pathway, MAPK/ERK signaling pathway, AR-FL, AR-Vs, and downregulates the expression of p-PI3K and p-AKT. Raddeanin A inhibits osteoclast formation, bone resorption, osteolysis, cancer cell invasion, migration, proliferation, angiogenesis and epithelial-mesenchymal transition, while induces apoptosis, cell cycle arrest, ROS production, immunogenic cell death and dendritic cell maturation. Raddeanin A improves blood-retinal barrier function, alleviates inflammation, regulates the tumor microenvironment, and enhances the activity of anti-PD-1 antibody. Raddeanin A is applicable to the research of breast cancer-associated osteolysis, human osteosarcoma, colorectal cancer, glioblastoma, Alzheimer's disease, cholangiocarcinoma, melanoma, non-small cell lung cancer, castration-resistant prostate cancer and multiple myeloma.

R547 is a potent, selective and orally active ATP-competitive CDK inhibitor, with K_is of 2 nM, 3 nM and 1 nM for CDK1/cyclin B, CDK2/cyclin E and CDK4/cyclin D1, respectively.

Alsterpaullone (9-Nitropaullone) is a potent CDK inhibitor, with IC₅₀s of 35 nM, 15 nM, 200 nM and 40 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E and CDK5/p35, respectively. Alsterpaullone also competes with ATP for binding to GSK-3alpha/GSK-3beta with IC₅₀s of both 4 nM. Alsterpaullone has antitumor activity, and possesses potential for the study in neurodegenerative and proliferative disorders. Alsterpaullone induces apoptosis in leukemia cell line.

(E/Z)-Zotiraciclib ((E/Z)-TG02) is a potent inhibitor of CDK2, JAK2 and FLT3 with IC₅₀s of 13, 73 and 56 nM, respectively. (E/Z)-Zotiraciclib effectively inhibits the proliferation of cancer cells, it can be used for the research of cancer.

Trilaciclib (G1T28) hydrochloride is an orally active CDK4/6 inhibitor with IC₅₀ values of 1 nM and 4 nM for CDK4 and CDK6, respectively. Trilaciclib hydrochloride can effectively inhibit tumor cell proliferation and reduce the hematological toxicity caused by chemotherapy. Trilaciclib hydrochloride attenuates apoptosis and myelosuppression induced by 5FU (HY-90006) chemotherapy.

Indirubin-3'-monoxime is a potent GSK-3β inhibitor, and weakly inhibits 5-Lipoxygenase, with IC₅₀s of 22 nM and 7.8-10 µM, respectively; Indirubin-3'-monoxime also shows inhibitory activities against CDK5/p25 and CDK1/cyclin B, with IC₅₀s of 100 and 180 nM.