CDK Inhibitor

AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC₅₀s of 2±1 nM and 3±1 nM, respectively.

Q901 (CDK7-IN-21) is a selective and potent CDK7 inhibitor with an IC₅₀ of 10 nM. Q901 disrupts MYC and E2FTOP1-DPCs and sensitizes tumor to TOP1 inhibitors by suppressing RNAPII transition from initiation to elongation. Q901 can inhibit tumor growth and significantly enhances tumor growth inhibition combined with TOP1 inhibitors. Q901 can be used for the research of cancer, such as colon cancer and lung cancer.

Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC₅₀s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes.

Senexin C is a selective and orally active CDK8/19 inhibitor. Senexin C shows a strong tumor-enrichment pharmacokinetic (PK) profile and tumor-pharmacodynamic (PD) marker responses. Senexin C inhibits the growth of MV4-11 leukemia cells with good tolerability.

3-Isomangostin is a flavonoid compound that acts as an inhibitor of MTH1 and acetylcholinesterase, with an IC₅₀ of 52 nM against MTH1 and IC₅₀ values of 5.75 μM and 12.96 μM against AChE and BChE, respectively. 3-Isomangostin also inhibits human aldose reductase and CDK4/Cyclin D1 with IC₅₀ values of 3.48 μM and 15.6 μM, respectively. 3-Isomangostin inhibits polyol pathway flux, competes with 8-oxo-dGTP for binding to the MTH1 active site through hydrogen bonding and hydrophobic xanthone interactions, blocks cell cycle progression, reduces cancer cell viability, and exhibits growth inhibitory effects against both normal and penicillin-resistant Staphylococcus aureus. 3-Isomangostin is used in research on Alzheimer's disease, diabetic complications, Staphylococcus aureus infections, and colon cancer.

(E/Z)-Zotiraciclib ((E/Z)-TG02) is an orally active 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.

Olomoucine is an ATP competitive inhibitor of CDKs. Olomoucine is a purine (HY-34431) derivative and inhibits CDC2/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E (both IC₅₀=7 μM), CDK/p35 kinase (IC₅₀=3 μM) and ERK1/p44 MAP kinase (IC₅₀=25 μM). Olomoucine regulates cell cycle and shows anti-melanin tumor activity.

CDK-TCIP1 is a bivalent molecule linking CDK9 inhibitor SNS-032 (HY-10008) to BCL6 ligand BI3812 (HY-111381). CDK-TCIP1 potently and specifically kills BCL6-overexpressing cells with EC₅₀ of 7.7 nM for SUDHL5 cells.

SRI-29329 is a specific CLK inhibitor, with IC₅₀ values of 78 nM, 16 nM and 86 nM for CLK1, CLK2 and CLK4, respectively.

Abemaciclib metabolite M18 (LSN3106729), the metabolite of Abemaciclib (HY-16297A), is a CDK inhibitor with antitumor activity. Abemaciclib metabolite M18 and a CRBN ligand have been used to design PROTAC CDK4/6 degrader.

LL-K12-18 is a CDK12 kinase inhibitor and a dual-site molecular glue. LL-K12-18 inhibits human CDK12 with an IC₅₀ value of 283.9 nM, and selectively degrades cyclin K via the ubiquitin-proteasome system by stabilizing the CDK12-DDB1 complex. LL-K12-18 downregulates DNA damage response genes, reduces the phosphorylation level of CTD Ser2 in RNA polymerase II, and modulates biomarkers such as ATM, RAD51, γ-H2AX and cleaved PARP, thereby effectively inducing apoptosis and inhibiting proliferation of breast cancer cells. LL-K12-18 exhibits high target selectivity and serves as a research tool for studies on triple-negative breast cancer.

BML-259 is a potent cyclin-dependent kinase 5 (Cdk5) inhibitor, with IC₅₀s of 64 and 98 nM for Cdk5 and Cdk2, respectively.

CDK12-IN-3 is a potent and selective CDK12 inhibitor with an IC₅₀ of 491 nM in enzymatic assay.

AT7519 Hydrochloride is a potent inhibitor of CDKs, with IC₅₀s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.

(S)-Roscovitine ((S)-Seliciclib; (S)-CYC202) is a potent and cross the blood-brain barrier CDKs inhibitor. (S)-Roscovitine shows neuroprotective efficacy. (S)-Roscovitine has the potential for the research of stroke.

Palbociclib-d₈ is a deuterium labeled Palbociclib. Palbociclib is a selective and orally active CDK4 and CDK6 inhibitor with IC₅₀s of 11 and 16 nM, respectively. Palbociclib has the potential for ER-positive and HER2-negative breast cancer research.

(-)-Enitociclib ((R)-Enitociclib) is an enantiomer of Enitociclib (HY-103019E) with an optical rotation of (-). Enitociclib is a selective CDK9 inhibitor and apoptosis inducer. Enitociclib inhibits CDK9 activity and reduces the phosphorylation of Ser2 in the carboxyl-terminal domain (CTD) of RNA polymerase Pol II, thereby downregulating the transcription of key oncogenes such as MYC and MCL1. Enitociclib has anti-proliferative activity targeting MYC⁺ lymphoma and multiple myeloma (MM) cells, and has synergistic effects with Bortezomib (HY-10227) and Lenalidomide (HY-A0003), and can be used in the research of hematological malignancies.

Zotiraciclib (TG02; SB1317) is an orally active JAK2/FLT3/CDK2 inhibitor with IC₅₀ values of 13 nM, 73 nM and 56 nM, respectively. Zotiraciclib inhibits cancer cell proliferation, tumor growth and the activity of CYP2D6. Zotiraciclib exhibits high plasma protein binding rate, Caco-2 permeability and tissue distribution capacity, as well as metabolic stability in human and canine liver microsomes. Zotiraciclib achieves tumor growth inhibition in nude mouse models of colon cancer and lymphoma xenografts. Zotiraciclib can be used for research related to colon cancer, B-cell lymphoma, advanced leukemia, acute leukemia and multiple myeloma.

Dimethoxycurcumin (DiMC) is a curcuminoid compound found in Curcuma longa. Dimethoxycurcumin is also an orally active thioredoxin reductase inhibitor (IC₅₀ = 5.4 μM) and androgen receptor antagonist. Dimethoxycurcumin inhibits thioredoxin reductase, leading to oxidized thioredoxin accumulation, ROS production, DNA damage, glutathione depletion, mitochondrial membrane potential decrease, ATP depletion, S phase arrest, and apoptosis. Dimethoxycurcumin inhibits NF-κB, NADPH oxidase subunits, ATP synthase subunits, CDK4, cyclin-D1, FASN, ACC, and the IRS2-PI3K-Akt pathway, while activating AMPK, ERK, and JNK. Dimethoxycurcumin can be used for research on cancer, arsenic-induced hepatotoxicity, and tuberculosis.

Ironomycin is a derivative of Salinomycin (HY-15597). Ironomycin exhibits selective inhibitory activity against mantle cell lymphoma (MCL) cells. Ironomycin blocks the cell cycle and induces apoptosis and ferroptosis. Ironomycin induces double-strand DNA breaks and activates the unfolded protein response (UPR), particularly the IRE1α signaling pathway accumulation. The combination of Ironomycin with Ibrutinib (HY-10997) shows a synergistic effect. Ironomycin can be used for the study of MCL.