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.

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).

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.

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.

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.

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.

ARUK2010694 (Compound 20) is a potent and selective inhibitor of NUAK1, with a pIC50 value of 8.7. It also inhibits the activity of CDK2, CDK4, and CDK6, with inhibition rates of 13%, 63%, and 32% respectively at a concentration of 1 μM. ARUK2010694 is applicable in research on neurological disorders, including Alzheimer's disease (AD).

TSL2109 is an orally active and selective inhibitor of DYRK2 and CDK4/6, with an IC50 value of 22 nM for DYRK2 and over 93% kinase selectivity. In vitro, TSL2109 induces cell cycle arrest and promotes apoptosis (apoptosis). It effectively overcomes Enzalutamide resistance by inhibiting tumor growth both in vivo and in vitro. Additionally, TSL2109 demonstrates resistance to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. It shows good safety and is applicable for research in prostate and breast cancer [1][2].

Piperazine-CO-C1-Azacyclohexane-C1-Piperazine is a PROTAC linker used in the synthesis of PROTACs, such as the PROTAC CDK4/6/9 degrader 1.

PROTACCDK4/6/9 degrader 1 is a PROTAC degrader targeting CDK4/6/9. It effectively degrades CDK4, CDK6, and CDK9 within triple-negative breast cancer (TNBC) cells, thereby inhibiting their proliferation. Additionally, PROTACCDK4/6/9 degrader 1 induces G1 phase arrest, promotes apoptosis, and suppresses cell migration and invasion in TNBC cells. This compound is useful for researching triple-negative breast cancer (TNBC).

PROTACCDK6 Degrader 1 (compound 48a) is an effective and selective PROTAC CDK6 degrader with a DC50 of 0.037 μM. It shows selectivity for CDK4 with a DC50 greater than 10 μM. This compound induces G0/G1 phase cell cycle arrest and apoptosis by inhibiting the downstream signaling pathways of CDK6. In the MOLM-14 xenograft mouse model, PROTACCDK6 Degrader 1 reduces tumor burden and CDK6 levels. It is a valuable tool for researching CDK6-driven cancers, such as acute myeloid leukemia (AML).

PROTACCDK2/4 Degrader-1 (Compound 5) is a potent CDK2/4 PROTAC degrader with a DC50 of ≤ 10 nM for both CDK2 and CDK4. It demonstrates excellent activity in inhibiting cell proliferation in OVCAR3 and T47D cell lines. This compound is applicable for breast cancer and ovarian cancer research.

PROTACCDK2/4/6 Degrader-1 is an orally active CDK2/CDK4/CDK6 PROTAC degrader. It is a prodrug created through a one-step reaction from PROTACCDK2/4/6 Degrader-2 using chloromethylnorvaline ester. This compound is applicable in research related to malignant melanoma.

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].