Aurora Kinase

PHA-680632 is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3.

SNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively. It is less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2. Phase 1.

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.

TAK-901 is a novel inhibitor of Aurora A/B with IC50 of 21 nM/15 nM. It is not a potent inhibitor of cellular JAK2, c-Src or Abl. Phase 1.

CCT137690 is a highly selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 15 nM, 25 nM and 19 nM. It has little effect on hERG ion-channel.

ENMD-2076 Tartrate is a multi-targeted kinase inhibitor with IC50s of 1.86, 14, 58.2, 15.9, 92.7, 70.8, 56.4 nM for Aurora A, Flt3, KDR/VEGFR2, Flt4/VEGFR3, FGFR1, FGFR2, Src, PDGFRα, respectively.

SCH-1473759 hydrochloride is an aurora inhibitor with IC50s of 4 and 13 nM for aurora A and B, respectively.

JB170 is a potent PROTAC-mediated degrader targeting AURORA-A kinase, with a DC50 of 28 nM. By conjugating Alisertib with the Cereblon-binding molecule Thalidomide, JB170 selectively binds AURORA-A (EC50=193 nM) over AURORA-B (EC50=1.4 µM). The compound induces S-phase cell cycle arrest specifically via the depletion of AURORA-A and effectively inhibits its non-catalytic functions. JB170 serves as a valuable tool for studying AURORA-A's roles in cellular processes and therapeutic applications in cancer research.

Tinengotinib (TT00420) is an orally bioavailable, spectrally selective small-molecule kinase inhibitor targeting Aurora A/B (IC50=1.2–3.3 nM), FGFR1/2/3 (IC50=1.5–3.5 nM), VEGFRs, JAK1/2, and CSF1R. It disrupts Aurora kinase-mediated cell cycle progression, inducing G2/M arrest, inhibits the FGFR/JNK-JUN signaling pathway, and activates the MEK/ERK-dependent apoptotic pathway. Tinengotinib exhibits potent anti-tumor proliferation, pro-apoptotic, anti-angiogenic, and tumor microenvironment-modulating activities. It is a promising candidate for research in triple-negative breast cancer (TNBC), gallbladder cancer, and tumor immune microenvironment studies.

SP-96 is a highly potent, selective, and non-ATP-competitive inhibitor of Aurora B kinase, with an IC₅₀ of 0.316 nM. It exhibits exceptional selectivity, showing over 2000-fold greater specificity for Aurora B compared to off-target kinases such as FLT3 and KIT. In NCI-60 cancer cell line screening, SP-96 demonstrates selective antiproliferative activity, notably against the triple-negative breast cancer (TNBC) cell line MDA-MB-468 (GI₅₀ = 107 nM). SP-96 is a valuable tool for investigating Aurora B–driven oncogenic pathways and holds promise for the development of targeted therapies in TNBC and other malignancies.

CD532 is a potent Aurora A kinase (AURKA) inhibitor with an IC₅₀ of 45 nM. It exerts a dual mechanism of action by both inhibiting AURKA enzymatic activity and promoting the degradation of the MYCN oncoprotein. CD532 directly binds to AURKA and induces a global conformational shift, disrupting its functional interactions. This unique mode of action makes CD532 a valuable tool for cancer research, particularly in MYCN-amplified tumors such as neuroblastoma.

Chiauranib (CS2164) is an orally active, multi-targeted small molecule inhibitor with potent anticancer activity. It targets key kinases involved in tumor angiogenesis, including VEGFR1, VEGFR2, VEGFR3, PDGFRα, and c-Kit, as well as mitosis-related kinase Aurora B and inflammation-associated kinase CSF-1R. Chiauranib exhibits IC₅₀ values ranging from 1 to 9 nM against these targets. Through simultaneous inhibition of angiogenesis, cell division, and inflammation pathways, Chiauranib exerts strong antitumor effects and is a promising candidate for the treatment of various solid tumors.

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.

Aurora A Inhibitor I is a potent and selective inhibitor of Aurora A kinase (AurA), with IC50 values to be 3.4 nM (Aurora A) and unusually high selectivity 1000 fold against Aurora B; a useful tool compound for investigating the cellular role of Aurora A kinases.

CCT129202 is a representative of a structurally novel series of imidazopyridine small-molecule inhibitors of Aurora kinase activity. It shows high selectivity for the Aurora kinases over a panel of other kinases tested and inhibits proliferation in multiple cultured human tumor cell lines.

Aurora kinase/VEGFR 2 inhibitor CYC116 inhibits Aurora kinases A and B and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in disruption of the cell cycle, rapid cell death, and the inhibition of angiogenesis.

ENMD-2076 has selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold selective for Aurora A than over Aurora B and less potent to VEGFR2/KDR and VEGFR3, FGFR1 and FGFR2 and PDGFRα. Phase 2.

KW-2449 is a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase.

MLN8054 is an inhibitor of Aurora A kinase, induces senescence in human tumor cells both in vitro and in vivo.

Aurora kinase-IN-8 is an orally active inhibitor of Aurora kinases, specifically targeting Aurora A and B kinases with IC50 values of 2.8 nM and 28.1 nM, respectively. This compound effectively disrupts spindle formation, induces G2/M phase arrest, and promotes apoptosis in cancer cells. It is particularly relevant for research applications focused on malignancies, including triple-negative breast cancer.

XL228 is a protein kinase inhibitor targeting IGF1R, the AURORA kinases, FGFR1-3, ABL and SRC family kinases. XL228 is an Aurora A inhibitor (IC50, f3 nmol/L) that has shown potent biochemical activity against ABL1 (Ki, 5 nmol/L), as well as the BCR-ABL1 T315I (Ki, 1.4 nmol/L) kinases.