cdk4/6 in 2

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

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.

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-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-IN-20 (Compound II-5) is an inhibitor targeting CDK4 and CDK6, exhibiting IC 50 values of 1.9 and 14.2 nM, respectively. Additionally, it suppresses cell proliferation and is applicable in cancer research.

CDK4/6-IN-21 maleate (compound I-52) is a potent inhibitor of CDK4 and CDK6, with IC50 values of 3.88 nM and 3.31 nM, respectively. This compound exhibits antitumor activity.

CDK4/6-IN-22 (Compound 1-A) is a dual inhibitor of CDK4 and CDK6.

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].

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.

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.

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].

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.

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.

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.

CDK/HDAC-IN-2 is a potent dual HDAC/CDK inhibitor that acts on HDAC1 (IC50: 6.4 nM), HDAC2 (IC50: 0.25 nM), HDAC3 (IC50: 45 nM), HDAC6 and 8 (IC50 > 1000 nM), CDK1 (IC50: 8.63 nM), CDK2 (IC50: 0.30 nM), and CDK4, 6, and 7 (IC50 > 1000 nM). CDK/HDAC-IN-2 can arrest the cell cycle in the G2/M phase and induce apoptosis, demonstrating excellent anti-proliferative and significant anti-tumor effects.

CDK4/6-IN-14 is a potent, highly selective inhibitor of Cyclin-Dependent Kinases 4 and 6 (CDK4/6), with inhibition concentrations (IC50s) of 10 nM and 16 nM, respectively. It shows over 60-fold selectivity for CDK4/6 compared to CDKs 1, 2, 7, and 9, and exhibits significant selectivity against 205 other kinases.

CDK4/6-IN-17 (compound 12) is an orally bioavailable inhibitor of CDK4/6, exhibiting potent activity with IC50 values between 10-100 nM in BE(2) cells, and has demonstrated efficacy in inhibiting tumor growth in the COLO205 xenograft model [1].

MAPK-IN-2 (compound 3h) is an efficacious MAPK inhibitor with antineoplastic properties that significantly hinders proliferation across various cancer cell lines. It demonstrates robust suppression of the MAPK pathway (EGFR WT IC50 = 281 nM, c-MET IC50 = 205 nM, B-RAF WT IC50 = 112 nM, CDK4/6 IC50 = 95 and 184 nM, respectively) and exhibits pronounced activity against mutated forms of EGFR and B-RAF (EGFR T790M IC50 = 69 nM and B-RAF V600E IC50 = 83 nM) [1].

Abemaciclib (Standard) is a reference standard for research and analysis in studies involving Abemaciclib. Abemaciclib (LY2835219) is a dual inhibitor of CDK4/6 (IC50=2/10 nM) with selectivity and specificity. Abemaciclib has antitumor activity and is used to treat advanced or metastatic breast cancer.