Aurora Kinase

JAB-2485 is a highly potent and selective inhibitor of Aurora kinase A (AURKA), with an IC₅₀ of 0.33 nM. It exhibits exceptional selectivity, showing approximately 1700-fold preference for AURKA over Aurora kinase B (AURKB). JAB-2485 induces cell cycle arrest and apoptosis, making it a promising candidate for cancer research, particularly in tumors driven by dysregulated mitotic signaling.

Aurkin A is an allosteric inhibitor that disrupts the interaction between Aurora A kinase (AURKA) and its co-activator TPX2 by selectively targeting the TPX2 binding site on Aurora A. It binds with a dissociation constant (K\_d) of 3.77 μM, thereby interfering with Aurora A activation and its downstream mitotic functions. Aurkin A offers a unique mechanism of action compared to ATP-competitive inhibitors and serves as a valuable tool for studying Aurora A–TPX2–mediated signaling in cell division and cancer progression.

CAM2602 is a selective inhibitor targeting the interaction between Aurora A kinase and its co-activator TPX2, with a high binding affinity of 19 nM for Aurora A. It effectively inhibits the growth of pancreatic cancer cells and demonstrates antitumor activity in solid tumor transplant models. Mechanistically, CAM2602 increases the proportion of phospho-histone H3 (PH3) positive cells—indicative of mitotic arrest—while decreasing the levels of Aurora A phosphorylated at threonine 288 (P-Thr288), a marker of Aurora A activation. These effects collectively contribute to its ability to disrupt mitosis and suppress tumor progression.

DBPR728 is an acyl prodrug of 6K465, engineered to improve pharmacokinetic properties by reducing the number of hydrogen bond donors, thereby enhancing membrane permeability and stability. As a prodrug of 6K465, DBPR728 functions as an Aurora kinase inhibitor that destabilizes MYC family oncoproteins, including c-MYC and N-MYC. It exhibits potent antitumor activity, particularly in cancers characterized by MYC overexpression. Notably, DBPR728 offers a 10-fold increase in oral bioavailability compared to 6K465, making it a promising candidate for the development of orally administered therapies targeting MYC-driven malignancies.

Phthalazinone pyrazole is a potent, selective, and orally bioavailable inhibitor of Aurora-A kinase, with an IC₅₀ of 0.031 μM. It exerts antitumor effects by arresting mitosis and inducing apoptosis in proliferating cells, leading to inhibition of tumor growth. Additionally, phthalazinone pyrazole suppresses epithelial-mesenchymal transition (EMT) during the differentiation of hepatocyte-like cells (HLCs) derived from human embryonic stem cells, indicating potential applications in both cancer therapy and stem cell biology.

AJI-214 is a dual-target inhibitor that simultaneously inhibits Aurora kinase A and Janus kinase 2 (JAK2). It directly blocks Aurora A activity, disrupting T cell mitotic progression and polarity, while also inhibiting JAK2-mediated STAT3 phosphorylation, thereby suppressing the differentiation of pro-inflammatory TH1 and TH17 cells. AJI-214 holds therapeutic potential for modulating immune responses and is being investigated for the prevention and treatment of graft-versus-host disease (GVHD).

6K465 is a pyrimidine-based small molecule inhibitor selectively targeting Aurora A kinase (AURKA). By inhibiting AURKA activity, 6K465 effectively reduces the expression levels of the oncogenic transcription factors c-MYC and N-MYC, contributing to its anticancer effects. This compound shows promise as a therapeutic agent for MYC-driven cancers by disrupting mitotic regulation and oncogene stabilization.

Derrone is a prenylated isoflavone that functions as an Aurora kinase inhibitor, exhibiting IC₅₀ values of 6 μM for Aurora B and 22.3 μM for Aurora A. By targeting these key mitotic kinases, Derrone disrupts cell cycle progression and displays notable antitumor activity, making it a promising compound for cancer research focused on mitotic regulation.

dAURK-4 hydrochloride is a potent and selective PROTAC degrader targeting Aurora A kinase (AURKA), derived from the AURKA inhibitor Alisertib. It effectively induces AURKA degradation and exhibits notable anticancer activity, making it a valuable agent for studying AURKA-driven oncogenic pathways and therapeutic development.

PHA-680626 is a selective inhibitor of Aurora-A kinase, disrupting its interaction with N-Myc. This compound effectively inhibits the kinase activities of both AURKA and Bcr-Abl, leading to the degradation of N-Myc. Additionally, PHA-680626 reduces phosphorylation levels of CrkL and histone H3. Its anti-proliferative and pro-apoptotic effects have been demonstrated in Imatinib-resistant chronic myeloid leukemia cell lines and primary CD34+ hematopoietic stem cells, making it a valuable tool for research in cancer therapeutics.