aurora-in-1

Zatosetron is a serotonin antagonists.

BET Aurora kinase-IN-1 (Compound 38) is a dual inhibitor of BET and Aurora kinases. It exhibits antiproliferative activity against various tumor cell lines and demonstrates significant antitumor efficacy in xenograft models of renal cell carcinoma and colon cancer, with tumor growth inhibition (TGI) rates of 45.99% and 53.06%, respectively.

Aurora LIM kinase-IN-1 (Compound F114) is a potent dual inhibitor of aurora and LIM kinases. It inhibits the proliferation and invasion of glioblastoma multiforme (GBM), making it a potential candidate for drug development in GBM and other cancers. Aurora and LIM kinases are involved in neoplastic cell division and cell motility, respectively [1].

Aurora A PKC-IN-1 (Compound 2e) is a potent dual inhibitor of Aurora A (AurA) and PKC (α, β1, β2, θ), exhibiting inhibitory activity on AurA (IC50: 6.9 nM) and PKCα (IC50: 16.9 nM), and demonstrating anti-proliferative and anti-metastatic effects on breast cancer cells.

Aurora kinase-IN-1, a potent aurora kinase inhibitor, modulates cell cycle progression and induces apoptosis by upregulating G1 cell cycle inhibitory proteins (including p21 and p27), elevating G1 progressive cyclin D1, and downregulating G1-to-S progressive cyclins, thereby arresting the cell cycle at the G1 S boundary. It stands as a promising lead compound for the development of chemotherapeutic agents.

FAK aurora kinase-IN-1, a dual inhibitor of FAK and aurora kinase, has IC50 values of 6.61 nM and 0.91 nM respectively, and demonstrates anticancer effects (WO2018019252A1; compound 11) [1].

FAK-IN-22 (Compound 26) is an inhibitor of FAK, JAK3, and Aurora B, with IC50 values of 50.94 nM, 9.99 nM, and 0.49 nM, respectively, effectively suppressing tumorigenesis and metastasis in pancreatic ductal adenocarcinoma (PDAC). It inhibits proliferation in PANC-1 cells with an IC50 of 0.15 μM. FAK-IN-22 induces apoptosis and G2 M phase arrest in PANC-1 cells by inhibiting the FAK PI3K Akt signaling pathway.

Aurora-A ligand 1 is a potent and selective inhibitor of Aurora-A, exhibiting a dissociation constant (Kd) of 0.85 nM. It serves as a target protein ligand [PROTAC target protein ligand] in the development of PROTAC Aurora-A degraders with antitumor activity. Additionally, Aurora-A ligand 1 is utilized in the synthesis of HLB-0532259, which exhibits antitumor effects against neuroblastoma.

AZD 1152 is an orally bioavailable prodrug of AZD 1152-HQPA, a selective inhibitor of Aurora kinase B (IC50= 0.36 nM).1AZD 1152 is converted to AZD 1152-HQPA in plasma. Inhibition of Aurora B results in disruption of spindle checkpoint functions and chromosome alignment, resulting in inhibition of cytokinesis followed by apoptosis.2,3AZD 1152 inhibits tumor xenograft growthin vivo.4,5 1.Mortlock, A.A., Foote, K.M., Heron, N.M., et al.Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinaseJ. Med. Chem.50(9)2213-2224(2007) 2.Popescu, R., Heiss, E.H., Ferk, F., et al.Ikarugamycin induces DNA damage, intracellular calcium increase, p38 MAP kinase activation and apoptosis in HL-60 human promyelocytic leukemia cellsMutation Research709-71060-66(2011) 3.Moore, A.S., Blagg, J., Linardopoulos, S., et al.Aurora kinase inhibitors: Novel small molecules with promising activity in acute myeloid and Philadelphia-positive leukemiasLeukemia24(4)671-678(2010) 4.Wilkinson, R.W., Odedra, R., Heaton, S.P., et al.AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosisClin. Cancer. Res13(12)3682-3688(2007) 5.Yang, J., Ikezoe, T., Nishioka, C., et al.AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivoBlood110(6)2034-2040(2007)

CD532 hydrochloride is a potent inhibitor of Aurora A kinase, having an IC50 of 45 nM. It not only blocks the activity of Aurora A kinase but also facilitates the degradation of the protein MYCN. Furthermore, CD532 hydrochloride interacts directly with AURKA, inducing a significant conformational change. Its utility in cancer research has been demonstrated [1][2].

GSK2646264 (Compound 44) is a highly effective and specific inhibitor of spleen tyrosine kinase (SYK) with a pIC50 of 7.1. It also inhibits multiple kinases, including LCK (pIC50 5.4), LRRK2 (pIC50 5.4), GSK3β (pIC50 5.3), JAK2 (pIC50 5), VEGFR2 (pIC50 4.5), Aurora B (pIC50 <4.6), and Aurora A (pIC50 <4.3). Notably, GSK2646264 demonstrates skin penetrability, reaching both the epidermis and dermis [1].

AKI603 is a novel small molecule inhibitor of Aurora kinase A (AurA)(IC50 = 12.3 nM). AKI603 is developed to overcome resistance mediated by BCR-ABL-T315I mutation. AKI603 exhibits strong anti-proliferative activity in leukemic cells[1][2].

SAR156497 is an exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo efficacy with IC50 = 0.5 nM (Aurora A); 1 nM (Aurora B incenp); 3 nM (Aurora C incenp) respectively SAR156497 combines high in vitro potency with satisfactory metabolic stability and limited CYP 3A4 and PDE3 inhibition. In vitro, SAR156497 displayed high antiproliferative activity on a large panel of tumor cell lines without correlation with any particular genetic signature or Aurora kinases expression. It induced significant modulation of Aurora A and Aurora B biomarkers (p-Aurora A and pHH3, respectively) and cell polyploidy, as expected from Aurora A B inhibitors.

XMD-12, also known as DUN57447, Aurora inhibitor (compound 1) or Aurora-IN-1, is an Auroro inhibitor, which targets Aurora A B C. (5.6 18.4 24.6 nM).

JB170, a potent and highly specific PROTAC-mediated AURORA-A (Aurora Kinase) degrader (DC50=28 nM), achieves its selectivity by linking Alisertib to the Cereblon-binding molecule Thalidomide. It demonstrates a strong preference for AURORA-A (EC50=193 nM) over AURORA-B (EC50=1.4 µM). The mechanism of JB170 involves S-phase arrest, specifically through AURORA-A depletion, and it is notably effective in inhibiting the non-catalytic functions of AURORA-A kinase [1].

Aurora Kinases-IN-4 (Compound 11c) is a covalent, ATP-competitive inhibitor of aurora kinase A with an IC50 value of 1.7 nM. It inhibits cell proliferation in SJSA-1, MDA-MB-231, A549, and HeLa cell lines with IC50 values of 4.27, 1.54, 3.08, and 6.99 μM, respectively. This compound is applicable in research concerning triple-negative breast cancer (TNBC) [1].

GRK2 Inhibitor 2 (Compound 8h), with an IC50 of 19 nM for GRK2 and 137 nM for Aurora-A, enhances β-AR-mediated cAMP accumulation in GRK2-overexpressing HEK293 cells. It is utilized in congestive heart failure (HF) research [1].

Compound Ac13, also termed AURKA against 1, acts as an inhibitor of the Aurora kinase (AURKA) with an IC50 of less than 0.5 nM, targeting the acetylation of endogenous lysine (K162) and exhibiting anti-tumor cell proliferation activity. The kinase activity of AURKA, acetylated at K162 and induced by AURKA against 1, is reversibly restored in HCT116 cells transfected with SIRT3.