CDK4/6-IN-6

Abemaciclib metabolite M20 (CDK4/6-IN-4) is an active metabolite of Abemaciclib. Abemaciclib metabolite M20 is a selective CDK4/6 inhibitor and can be used for researches on the treatment of cancer.

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].

CDK4/6-IN-2 is a potent inhibitor of CDK4 and CDK6 [IC50s: 2.7 and 16 nM].

CDK4/6-IN-3, a brain-penetrant CDK4/CDK6 inhibitor (Kis: <0.3 nM and 2.2 nM), is used for the treatment of glioblastoma and inhibits CDK1 with a Ki of 110 nM.

Lerociclib (G1T38) is a selective and highly potent CDK4/6 inhibitor with anticancer and antitumor activity, inhibits CDK4/CyclinD1 and CDK6/CyclinD3, and inhibits tumor growth in an animal model of endocrine-resistant breast cancer. Due to the poor solubility, for animal studies, the salt form T11345L is recommended.

AZD8421 is a potent and highly selective inhibitor of cyclin-dependent kinase 2 (CDK2) with an IC50 of 9nM, demonstrating greater selectivity over CDK1, CDK4, and CDK6. This compound also exhibits antiproliferative properties by effectively inhibiting Rb phosphorylation. In models of breast and ovarian cancer, AZD8421 has shown significant activity both as a monotherapy and in combination with CDK4/6 inhibitors.

CDK4/6-IN-23 (Compound 42) is a potent and selective inhibitor of CDK4/6, displaying an IC50 of 11 nM for CDK6. This compound significantly activates immune cells and enhances IL-3 production. In mice undergoing 5-FU chemotherapy, CDK4/6-IN-23 demonstrates dual bone marrow protection and immunomodulatory effects.

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.

CDK4/6-IN-24 (Compound A) is an inhibitor of CDK4/6 with broad-spectrum antitumor activity. It can effectively inhibit various cancer cells, exhibiting an IC50 in the submicromolar range.

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.

LEQ803 (N-DesmethylRibociclib) is a metabolite of the CDK4/6 inhibitor Ribociclib, produced through metabolism by CYP3A4. This compound holds potential applications in the field of oncology.

LA-CB1 is a derivative of Abemaciclib that targets CDK4/6 and promotes their degradation via the ubiquitin-proteasome pathway, thereby blocking the CDK4/6-Cyclin D1-Rb-E2F axis and inducing G0/G1 cell cycle arrest and apoptosis (Apoptosis). It demonstrates antiproliferative activity against MDA-MB-231 cells with an IC50 of 0.27 µM and effectively inhibits epithelial-mesenchymal transition, cell migration, invasion, and angiogenesis. In highly invasive models like triple-negative breast cancer (TNBC), LA-CB1 significantly suppresses tumor growth, showing robust dose-dependent antitumor activity. This compound can be utilized in breast cancer research.

CDK4/6-IN-15 hydrochloride is an orally active selective inhibitor of CDK4/6. It effectively restrains the growth of cancer cells by arresting the cell cycle at the G1 phase. Additionally, CDK4/6-IN-15 hydrochloride inhibits phosphorylation of the retinoblastoma tumor suppressor protein (Rb) at site S780 and suppresses E2 factor (E2F)-regulated gene expression.

LO-3-63 is a Ribociclib analogue featuring a truncated fumaramide group and acts as a CDK4/6 degrader with PROTAC properties. It degrades CDK4/6 in cells via a CUL4DCAF16-dependent pathway.

Carbonic anhydrase-IN-35 is a selective inhibitor of carbonic anhydrase (CA), demonstrating potent inhibition of tumor-associated hCA IX (Ki= 0.6 nM) and hCA XII (Ki= 2.2 nM). It induces autophagic apoptosis in MCF-7 cells by increasing Bax, decreasing Bcl-2, and downregulating CDK4/6. Carbonic anhydrase-IN-35 exhibits significant cytotoxicity against MCF-7 (IC50= 0.3975 μM normoxia / 0.6575 μM hypoxia), MCF-7-ADR (IC50= 0.3975 μM normoxia / 4.488 μM hypoxia), MDA-MB-231, and 4T1 breast cancer cells. This compound is applicable in breast cancer research.

Dalpiciclib (isethionate) is a CDK4/6 inhibitor that suppresses the kinase activity of CDK4 and CDK6, thereby blocking the cell cycle transition from the G1 phase to the S phase, which inhibits abnormal cell proliferation. Dalpiciclib (isethionate) is utilized in breast cancer research.

MFDCH016 is a potent inhibitor of HDAC1/6 (IC50= 38/59 nM) and CDK4/6 (IC50= 680/720 nM). It induces apoptosis in MCF-7 cells and causes cell cycle arrest in the G2/M and G0/G1 phases. MFDCH016 modulates the HDAC-p21-CDK signaling pathway, increasing levels of acetylated H3 and p21, making it useful for breast cancer research.

LCI133 is an innovative, highly potent, and selective multi-target kinase inhibitor effective at the nanomolar level. It targets CDK4/6/9 and AURKA/B with IC50 values of 4.7/10.2/4.1 nM and 2.8/10.6 nM, respectively. In MYCN-amplified neuroblastoma BE(2)-C cells, LCI133 induces S/G2 phase arrest and triggers significant apoptosis (apoptosis). Moreover, LCI133 demonstrates substantial antitumor efficacy in BE(2)-C neuroblastoma xenograft models.

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].

Palbociclib-C4-Boc is a target protein ligand-linker conjugate composed of the CDK4/6 ligand Palbociclib and a PROTAC linker, capable of recruiting E3 ligase. It is utilized in the synthesis of PROTACBSJ-03-204.

PROTACCDK4/6/9 degrader 2 (Compound P4) is an orally active and low-toxicity PROTAC prodrug targeting CDK4/6/9. It significantly inhibits tumor growth and reduces lung metastasis of tumors. This compound is applicable in cancer research, including studies on breast cancer.

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.

Thalidomide-OCH2-amide-PEG2-C2-Boc is an E3 ligase ligand-linker conjugate that includes a cereblon (CRBN) ligand for the E3 ubiquitin ligase and a linker. Thalidomide-OCH2-amide-PEG2-C2-Boc is utilized in the synthesis of PROTAC CDK4/6/9 degrader 2.

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).