cdk4 in 1

CDK4 inhibitor is a novel and specific CDK4/Cyclin D1 inhibitor with an IC50 of 10 nM; 1500 and 500 fold than CDK1/Cyclin B (IC50>15 uM) and CDK2/Cyclin A (IC50=5.265 uM) respectively.

CDK4/6/1 Inhibitor (Crozbaciclib) is a type of CDK4/6 inhibitor (IC50s: 3 and 1 nM). CDK4/6 inhibitor is a class of compounds used for the treatment of some types of hormone receptor positive, HER2-negative breast cancer, which can block the process of breast cancer cell division and reproduction.

CDK4/6/HDAC-IN-1 (Compound N14) is a dual-target inhibitor of CDK4/6 and HDAC, with IC50 values of 7.23 nM for CDK4, 13.20 nM for CDK6, 55.66 nM for HDAC1, and 48.38 nM for HDAC6. It induces apoptosis and G0/G1 phase arrest through the HDAC-p21-CDK signaling pathway and can inhibit hepatocellular carcinoma.

CDK4/9-IN-1 (Compound 29) is a selective dual inhibitor of CDK4 and CDK9, exhibiting IC50 values of 23 nM and 12 nM, respectively. It holds potential for use in cancer research.

CDK4/6/BRD4-IN-1 (B15) is an inhibitor targeting CDK4, CDK6, and BRD4, with IC50 values of 220 nM for BRD4-BD2, 146 nM for BRD4-BD1, 106 nM for CDK6, and 85 nM for CDK4. This compound is applicable for research in non-small cell lung cancer (NSCLC) and can induce cell cycle arrest and apoptosis.

HEMTAC CDK4/6 degrader 1 is a PROTAC connected by ligands for HSP90 and CDK4/6 with a \( K_d \) value of 35.7 μM. It induces CDK4/6 degradation in B16F10 melanoma cells, arrests the cell cycle at the G0/G1 phase, and induces apoptosis. HEMTAC CDK4/6 degrader 1 can be used in cancer research [1].

PROTAC CDK4/6 degrader 1 (Compound 7f) is a dual degrader of CDK4 and CDK6, with DC50 values of 10.5 nM and 2.5 nM, respectively. This compound effectively inhibits proliferation in Jurkat cells (IC50 of 0.18 μM), induces cell cycle arrest during the G1 phase, and triggers cell apoptosis (apoptosis).

CDK4 degrader1 (ML 1–71) is a molecular glue degrader specifically targeting CDK4.

FLT3/CDK4-IN-1 is a highly selective, potent, orally active dual inhibitor of FLT3 (IC50: 7 nM) and CDK4 (IC50: 11 nM), demonstrating significant anti-tumor effects in vivo and anti-proliferative effects on certain cancer cells.

SHP2/CDK4-IN-1 (compound 10) is a dual inhibitor targeting SHP2 and CDK4, with oral activity and high potency, showing IC50 values of 4.3 nM for SHP2 and 18.2 nM for CDK4. It induces G0/G1 arrest, inhibits proliferation of TNBC cell lines, and demonstrates significant antitumor efficacy in the EMT6 syngeneic mouse model. This compound is valuable for research into triple-negative breast cancer (TNBC) [1].

GP-82996 (CINK4) is a pharmacological inhibitor specifically targeting CDK4/6, exhibiting IC50 values of 1.5 μM for CDK4/cyclin D1, 5.6 μM for CDK6/cyclin D1, and 25 μM for Cdk5/p35. It effectively induces apoptosis in U2OS cancer cells, positioning it as a potential investigational tool in cancer research [1] [2].

LSN2839567 (Abemaciclib metabolite M2) is the active metabolite of Abemaciclib, a potent CDK4 and CDK6 inhibitor (IC50s: 1-3 nM) with anticancer activity.LSN2839567 inhibits CDK9.LSN2839567 inhibits cell growth and cell cycle progression in a concentration-dependent manner. cell growth and cell cycle progression in a concentration-dependent manner and can be used to study breast and lung cancer.

AG-024322 is a potent ATP-competitive inhibitor targeting pan-CDK, effectively inhibiting cell cycle kinases CDK1, CDK2, and CDK4 with Ki values in the 1-3 nM range (1-3 nM).

NUAK1-IN-1 (Compound 9) is an inhibitor of NUAK1 with an IC50 of 5.012 nM, as well as a CDK4 inhibitor. It is suitable for research related to cancer, neurodevelopmental disorders, and Alzheimer's disease.

Autophagyagonist-1 (compound 22) is an autophagy agonist. It exhibits significant anticancer activity against HepG2 cells and normal cells, with IC50 values of 8.8 μM and > 50 μM, respectively. The compound induces G1/S phase cell cycle arrest, suppresses the expression of CDK4 and CyclinD1, and upregulates P21. Additionally, Autophagyagonist-1 enhances autophagosome, LC3, and PINK1 accumulation, thereby promoting autophagy and mitophagy in HepG2 cells.

GPX4/CDK-IN-1 is a dual inhibitor of GPX4 and CDK, exhibiting IC50 values of 542.5 nM for GPX4, 191.2 nM for CDK4, and 68.1 nM for CDK6. [GPX4/CDK-IN-1] demonstrates significant anti-cancer cell growth activity in vivo.

CDK6/PIM1-IN-1 (Compound 51) hydrochloride is an orally active and potent dual inhibitor of CDK6 and PIM1, with IC50 values of 39 nM and 88 nM, respectively. It also inhibits CDK4 with an IC50 of 3.6 nM. This compound significantly suppresses the proliferation of acute myeloid leukemia (AML) cells, arrests the cell cycle at the G1 phase, and induces apoptosis. CDK6/PIM1-IN-1 hydrochloride demonstrates anti-AML activity.

Olomoucine II is a potent cyclin-dependent kinase inhibitor with IC50 values of 7.6, 0.1, 19.8, 0.45, and 0.06 μM for CDK1, CDK2, CDK4, CDK7, and CDK9, respectively. Olomoucine II demonstrates high selectivity over numerous other kinases while retaining measurable activity against ERK2 and ABCB1, allowing it to modulate multidrug resistance pathways. Olomoucine II suppresses proliferation across cancer cell lines regardless of p53 status and exhibits synergistic action with daunorubicin in ABCB1-expressing HCT-8 cells.Olomoucine II additionally inhibits replication of HSV-1, HSV-2, vaccinia virus, adenovirus 4, and human CMV, making Olomoucine II an important antiviral and anticancer research tool.

CAY10747 is an inhibitor of the protein-protein interaction between heat shock protein 90 (Hsp90) and cell division cycle 37 (Cdc37) and a derivative of celastrol .1It decreases protein levels of the Hsp90-Cdc37 complex and the Hsp90-Cdc37 clients phosphorylated Akt and Cdk4 in A549 cells when used at a concentration of 5 μM. CAY10747 inhibits proliferation of A549, MCF-7, HOS, and HepG2 cells (IC50s = 0.41, 0.64, 0.9, and 0.94 μM, respectively) and induces apoptosis in A549 cells. 1.Li, N., Xu, M., Wang, B., et al.Discovery of novel celastrol derivatives as Hsp90-Cdc37 interaction disruptors with antitumor activityJ. Med. Chem.62(23)10798-10815(2019)

LSN3106729 hydrochloride, the metabolite of Abemaciclib , is a CDK inhibitor with antitumor activity. LSN3106729 hydrochloride and a CRBN ligand have been used to design PROTAC CDK4/6 degrader[1]. [1]. Edward S. Kim, et al. Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non-Small Cell Lung Cancer: A Phase Ib Study. [2]. Nathanael Gray, et al. Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use. WO2017185031A1.

CDK4/6-IN-12 is a potent cyclin-dependent kinase 4/6 (CDK4/6) inhibitor with enzymatic inhibitory activity against CDK4 and CDK6, having IC50 values of 592.3 nM and 3090 nM, respectively. CDK4/6-IN-12 can be used in cancer research[1].

CDK1/2/4-IN-1 (compound 3a) is a potent CDK inhibitor with IC50 values of 1.47, 0.78, and 0.87 μM for CDK1, CDK2, and CDK4, respectively. It can be used in cancer research to arrest the cell cycle at the G2/M phase and induce apoptosis, elevating Bax, caspase-3, and P53 levels while decreasing Bcl-2 levels [1].

ZDLD13 is a β-carboline that exhibits potent anti-HCT116 activity inclusive of inhibition of invasion and migration, inhibition of colony formation, inducing of apoptosis as well as arresting of G1 phase in cell cycle. ZDLD13 is an orally active and selective inhibitor of CDK4/CycD3 (IC 50 = 0.38 μM) which exhibits significant inhibition of tumor growth in HCT116 tumor xenograft model [1].

p53 Activator 2 (compound 10ah) intercalates into DNA, causing significant double-strand breaks and upregulating the expression of p53, p-p53, CDK4, and p21, leading to cell cycle arrest at the G2/M phase. It induces apoptosis, reduces anti-apoptosis proteins Bcl-2, Bcl-xL, and cyclin B1 levels, and shows anti-proliferative activity against MGC-803 cells with an IC50 of 1.73 μM. Additionally, p53 Activator 2 exhibits potent anticancer effectiveness in MGC-803 xenograft tumor models [1].