16 results about "Aurora kinase" patented technology

The present invention relates to compositions, methods, uses and kits for the treatment of renal cystogenesis. In particular, the compositions, methods, uses and kits are particularly useful, but not limited to, the treatment or prevention of Polycystic Kidney Disease. In one aspect, the prevent invention provides a method of minimising or delaying renal cystogenesis in a subject in need thereof, the method comprising inhibiting AKT in the subject, or reducing the level of Aurora kinase in the subject, thereby minimising or delaying renal cystogenesis.

Substituted pyrrolo[2,3-d]pyrimidines as inhibitors for multi-resistant cancers are described herein. Also provided herein are methods of forming the compounds, methods for inhibiting aurora kinase A and / or aurora kinase B activity and epidermal growth factor activity, methods of treating, ameliorating, or preventing cancer, and uses of the compounds for inhibiting aurora kinase A and / or aurora kinase B activity and epidermal growth factor receptor kinase activity. The compounds are generally of the formulas as illustrated herein, including those of Formula (I-2) or a pharmaceutically acceptable salt thereof:wherein: X1 is N; X2 is N; X3 is —NH—; X4 is N or CR2; X5 is CH, CCH3, or CCOOH; L1 is —NR4—R1; L2 is NH2 or H; R1 is:R2 is H, COOH, a 5-membered heteroaryl, or X6R3; X6R3 is as described herein; R4 is H; R5 is as described herein; and m is 1, 2, 3, 4, or 5.

Compounds (I), compositions, and methods for use in degrading Aurora kinase are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising Aurora kinase degraders, as well as methods for treating cancer using Aurora kinase degraders.

The present invention discloses an s-triazine compound having Aurora kinase inhibitory activity and its application. The s-triazine compound or its pharmaceutically acceptable salts, hydrates, solvates, polymorphs, tautomers, prodrugs, isotopic derivatives, or mixtures thereof, wherein the s-triazine compound is represented by the following general formula (I): The present invention provides a newly synthesized s-triazine compound by introducing different functional groups at the 2, 4, and 6-positions of the s-triazine parent nucleus. This newly synthesized s-triazine compound exhibits good inhibitory activity against Aurora kinase.

The invention discloses a screening method of an aurora kinase AURKA inhibitor, and the preparation method is characterized by having the following general formula: the invention provides a virtual screening method of the aurora kinase AURKA inhibitor, which comprises the following steps: (1) an AURKA model: obtaining an AURKA crystal structure, preprocessing crystal data, defining the crystal data as a counter acceptor, and determining a binding site; (2) a small molecule compound library: pretreating small molecule structures; (3) performing rigid docking based on shape matching on the constructed AURKA crystal data and the small molecular structure, and selecting the structure in the front sequence to perform next optimization; (4) carrying out more accurate semi-flexible butt joint on the small molecular structure subjected to primary screening, and taking the binding energy as the standard of secondary screening; and (5) integrating two times of docking scoring to obtain the aurora kinase AURKA inhibitor.

To provide forms of Compound A, which is a potent Aurora A, B, and C, and FLT3 kinase inhibitor, that are stable and have a certain degree of inherent water solubility.SOLUTION: Provided are a fumarate salt and polymorphic forms of Compound A (6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine). The present invention also provides processes for preparation of salts and polymorphic forms of Compound A, pharmaceutical compositions comprising them, and their use in treatment of proliferative disorders such as cancer, and other diseases or conditions in which Aurora kinase and / or FLT3 activity is implicated.SELECTED DRAWING: None

Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1 / H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

Disclosed herein inter alia are compositions and methods useful in the treatment of cancer and for modulating the activity of Aurora A kinase and / or a Myc family protein.

The diagnostic markers that provide novel diagnostic criteria to blastic plasmacytoid dendritic cell neoplasm (BPDCN) has been searched, and the presence of immunoblastoid cytomorphology, 8q24 rearrangement, and MYC expression were established as novel markers for subtyping BPDCN. It has been further found that the inhibitors which directly or indirectly inhibit the expression, functions, or signaling pathways of MYC, such as BET bromodomain-selective inhibitors or aurora kinase inhibitors, are effective in MYC-positive BPDCN, and HDAC inhibitors or BCL2 family protein inhibitors are effective as therapeutic drugs for BPDCN.

Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1 / H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

Provided are compounds of Formula (I), a tautomer thereof, a deuterated derivative of the compound or the tautomer, and a pharmaceutically acceptable salt of the foregoing, compositions comprising the compounds of Formula (I), a tautomer thereof, a deuterated derivative of the compound or the tautomer, and / or a pharmaceutically acceptable salt of the foregoing, and methods of using the same, in treating, for example, the diseases, disorders, or conditions mediated by the degradation of protein kinases, such as Hematopoietic progenitor kinase 1 (HPK1, MAP4K1), Mitogen-activated protein kinases 1 / 2 (MEK 1 / 2), Human Fms-like tyrosine kinase 3 receptor (FLT3), and Aurora kinases.

The present invention relates to metabolically stable compounds that modulate the binding of AURKA to its interacting proteins, especially TPX2. The compounds of the present invention have high therapeutic efficiency due to its high metabolic stability and low toxicity. The present invention also pertains to the use of such compounds in the prevention and / or treatment of proliferative diseases, such as cancer, and kits comprising the same.

The present invention relates to salts and polymorphic forms of Compound A (6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine), an inhibitor of Aurora kinase and FMS-like tyrosine kinase 3 (FLT3) activity. The present invention also relates to processes for the preparation of the salts and polymorphic forms of the compound, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and / or FLT3 activity is implicated.

Described herein is a conjugate having the formula of: A(L-I)x; wherein: A is a targeting moiety; L is a covalent linker; I is an Aurora kinase inhibitor; and x is a number of Aurora kinase inhibitors per targeting moiety, and can be an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, and fractional integers in between, and their use in treating and / or imaging a cancer or tumor or inflammation. The targeting moiety can include a targeting antibody, a fragment of a targeting antibody, an antibody-like structure, a nanoparticle drug delivery platform, a target-specific small molecule, a macromolecule, a peptide, and a peptide fragment.

The invention belongs to the field of drug delivery, and discloses a nano-liposome delivery system targeting PLK1 / Aurora kinase and an application of the nano-liposome delivery system in oral squamous cell carcinoma treatment, the system jointly loads Volasertib and Alisertib in DOPE / CHEMS pH sensitive liposome, is coupled with GE11 targeting EGFR, realizes accurate delivery through active targeting and pH response drug release, induces mitosis disasters synergistically through double targets, and the inhibition rate exceeds 80%.

The present invention discloses a quinoline compound having a general structural formula selected from any one of the following: #imgabs0#, #imgabs1#, etc. The present invention also provides the use of the compound in preparing a drug having dual inhibitory effects on Aurora kinase B and epidermal growth factor receptor. The drug prepared using the compound has anti-non-small cell lung cancer effects.