81 results about "Wee1" patented technology

Solid forms of Compound (A) are described herein. The polymorphic forms described herein are WEE1 inhibitors. Processes and intermediates described herein are useful for making the Compound A and various polymorphic forms. Such forms are useful for treating diseases or conditions that are mediated by WEE1, including conditions characterized by excessive cellular proliferation, such as cancer.

Disclosed herein is use of a combination of Compound (A) (azenosertib), or a pharmaceutically acceptable salt thereof, and a KRAS G12C inhibitor, such as sotorasib or adagrasib, or a pharmaceutically acceptable salt thereof, for treating a disease or condition, such as a colorectal, pancreatic and / or non-small cell lung cancer.

Compounds of general Formula (I) are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as cancer.

The present disclosure provides, among other things, methods for treating cancer comprising administering an effective dose of a WEE1 inhibitor such as Azenosertib, or a pharmaceutically acceptable salt thereof, to a subject selected to have a cancer associated with at least one alteration in the F-box and WD repeat domain containing 7 (FBXW7) gene.

Methods of treating cancer using a combination of a WEE1 inhibitor and a topoisomerase 1 inhibitor are provided.

This application relates the use of a combination of a membrane-associated tyrosine and threonine- specific CDC2-inhibitory kinase (Myt1) inhibitor with a Weel inhibitors in treating cancer or inducing cell death. The synergistic effect of the combination results in a subtherapeutic dose or a reduced dosing schedule of the Myt1 inhibitor, the Wee1 inhibitor, or both relative to a monotherapy of either the Myt1 inhibitor or the Wee1 inhibitor in isolation.

The present disclosure provides, among other things, methods for treating cancer comprising administering an effective dose of Azenosertib to subjects selected to have a Cyclin E1 status above a predetermined threshold.

A compound for degrading a Wee1 protein kinase or a pharmaceutically acceptable salt thereof, and the use thereof in the treatment of proliferative diseases.

The present disclosure provides, among other things, methods for treating cancer comprising administering an effective dose of azenosertib, or a pharmaceutically acceptable salt thereof, to subjects selected to have a homologous recombination repair deficiency (HRD).

Compounds of general Formula (I') are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as breast cancer.

Indazolo-amino-pyrimidinone compounds of formula I; (I), for use in methods of inhibiting both Wee1 A kinase and Myt1 kinase.

Disclosed herein is use of a combination of Compound (A), or a pharmaceutically acceptable salt thereof, and a maytansinoid, or an antibody-drug conjugate comprising a maytansinoid (including pharmaceutically acceptable salts) for treating a cancer.

The salt, such as adipate salt Form A, and freebase forms of Compound A are WEE1 inhibitors. Such salts and / or forms and freebase forms, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as breast cancer.

Methods and systems for determining and / or confirming a response to a checkpoint kinase 1 (Chk1) inhibitor, a Wee1 inhibitor, an ATR inhibitor, or a combination thereof, and methods of administering a Chk1 inhibitor, a Wee1 inhibitor, an ATR inhibitor, or a combination thereof to a subject determined to be responsive to such therapy are provided herein. The present disclosure, inter alia, solves this problem by identifying responder and non-responder populations to Chk1 inhibition therapy (e.g., prexasertib), Wee1 inhibition therapy, ATR inhibition therapy, or combinations thereof (e.g., prior to initiation of therapy) by defining a simple treatment benefit prediction biomarker signature (also referred to throughout as a response prediction signature) that effectively predicts treatment benefit.

The invention provides a gene marker combination and system for predicting glioma risk and application, and belongs to the technical field of glioma prediction. The gene marker combination comprises an NTN4 gene, an RBP1 gene, a TWIST1 gene, a GADD45G gene, an NUAK2 gene, a GRIK2 gene, a WEE1 gene and an RRM2 gene. Eight senescence-related genes are screened by screening senescence-related genes and combining survival data of glioma patients. The research finds that the risk scoring model constructed by using the eight senescence-related genes can specifically and sensitively predict the glioma risk, and has good prediction efficiency. According to the method, the glioma risk assessment model constructed on the basis of combining the risk scoring model with the clinical pathological variable factors is established, and compared with the capability of predicting the glioma risk of the risk scoring model, the glioma risk assessment model is better in prediction efficiency.

Provided herein are compounds and compositions thereof that reduce WEE1 kinase protein levels. In some embodiments, the compounds and compositions are provided for treatment WEE1 associated diseases such as cancer.

Provided herein are methods and systems for determining and / or validating response to a checkpoint kinase 1 (Chk1) inhibitor, a Wee1 inhibitor, an ATR inhibitor, or a combination thereof, and methods of administering a Chk1 inhibitor, a Wee1 inhibitor, an ATR inhibitor, or a combination thereof to a subject determined to be responsive to said therapy.

Methods of treating small cell lung cancer (SCLC) with a WEE1 inhibitor are provided.

Disclosed is an application of a protein kinase inhibitor in preparation of a medicine for inhibiting uterine leiomyosarcoma, wherein the protein kinase inhibitor can effectively inhibit tumor growth in vitro and in vivo, and has better efficacy and safety compared with traditional chemotherapy. The protein kinase is one of the following: Wee1-like protein kinase, cyclin-dependent kinase 1, serine / threonine protein kinase 1 and serine / threonine protein kinase ATR.

Disclosed are bifunctional compounds (degraders) that target Wee1 tyrosine kinase for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.

The present disclosure provides, inter alia, methods for treating cancer comprising administering to a subject selected to have a cyclin E1 state above a predetermined threshold an effective dose of Asensertib.

Methods of treating a solid tumor using a WEE1 inhibitor are provided.

Provided are compounds of Formula I, or stereoisomers, tautomers, N-oxides, hydrates, solvates, isotopically labeled compounds, or pharmaceutically acceptable salts thereof, or mixtures thereof. Compounds of Formula I are inhibitors of Wee1 kinase. Thus, these compounds are useful in the treatment of diseases caused by abnormal Weel activity. (I).

The invention relates to the field of medicinal chemistry, in particular to a 2-aminopyrimidine-5-formamide compound and application thereof in preparation of drugs for treating and / or preventing cancers. The compound is a 2-aminopyrimidine-5-formamide compound represented by a general formula I, and pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein substituent groups R1, R2 and R3 have meanings given in the specification. The invention further relates to application of the compound shown in the general formula I in preparation of drugs for treating and / or preventing diseases related to Wee1 kinase. # imgabs0 #

The invention discloses a functional phosphorylation modification site screening method based on base editing, which is used for accurately identifying functional phosphorylation modification sites. According to the method, a cell line (such as human gastric cancer cells AGS / HGC27) for stably expressing ABE is constructed, an sgRNA library (containing 39 and 689 sites) covering phosphorylation sites of a whole genome is designed, screening is carried out under the conditions of oxaliplatin and the like, and the technical problem that more than 95% of phosphorylation sites are unknown in function is solved. According to the method, key sites (such as WEE1 S53) related to gastric cancer chemotherapy drug resistance are successfully recognized, the synergistic effect of oxaliplatin and WEE1 inhibitor combination is verified through experiments, and an innovative platform is provided for disease mechanism research and drug development.

Described herein are WEE1 degraders and pharmaceutical compositions comprising the same. The subject compounds and compositions are useful for the treatment of a disease or condition associated with WEE1 activity, such as cancers.

Provided herein are methods and systems for determining and / or validating response to a checkpoint kinase 1 (CHEK1) inhibitor, a WEE I inhibitor, an ATR inhibitor, or a combination thereof, and methods of administering a CHEK1 inhibitor, a. WEE1 inhibitor, an ATR inhibitor, or a combination thereof to a subject determined to be responsive to said therapy.

The application discloses combination therapies using a combination of a WEE1 inhibitor and a BRAF inhibitor, and optionally an EGFR inhibitor, for the treatment of diseases, such as colorectal cancer.

The invention discloses a novel pyrimido large heterocyclic compound with WEE1 and Yes double-target inhibition activity for the first time, and particularly discloses a compound which is used as a WEE1 and Yes double-target inhibitor and has a structure shown in a formula (I) or pharmaceutically acceptable salt, solvate, hydrate, isotope substitute or isomer and polymorphic substance of the compound.