9 results about "ROS1" patented technology

The present disclosure relates to a macrocyclic compound represented by formula I, a pharmaceutical composition containing the compound or a pharmaceutically acceptable salt, prodrug, solvate, polymorph, isomer and stable isotopic derivative thereof, a preparation method therefor, and a use thereof as a TRK, ROS1, c-Met, CSF1 and / or ALK inhibitor.

The invention belongs to the field of biological medicines, and particularly relates to a medicine for treating meningeal metastasis of malignant tumors with NTRK and / or ROS1 mutations and a preparation method, and the medicine is a freeze-dried powder preparation or injection for subarachnoid space injection of NTRK / ROS1-TKIs. The invention also provides an application of the NTRK / ROS1-TKIs in preparation of a medicine for treating meningeal metastasis of malignant tumors with NTRK and / or ROS1 mutation. The prepared NTRK / ROS1-TKIs injection can be directly injected into the subarachnoid space of a patient, the drug concentration in cerebrospinal fluid of the patient is greatly improved, the cerebrospinal fluid / plasma concentration ratio can reach 20 times or more, the problem of insufficient dosage caused by the blood-brain barrier after the targeted drug is orally taken can be completely solved, and the drug has the advantages of fast effect taking, no toxic or side effect and no toxic or side effect. The treatment effect on meningeal metastasis of malignant tumors such as lung cancer can be obviously improved.

The invention discloses a lung cancer detection primer probe composition and application thereof in a diagnostic kit, and belongs to the technical field of biological detection. The technical problem to be solved is to provide a high-sensitivity and high-specificity primer probe composition for one-time detection of multiple lung cancer mutant genes. The invention provides a primer probe composition which is high in sensitivity (capable of detecting DNA mutation with mutation frequency as low as 0.5% and RNA fusion of 25 copies) and high in specificity and is used for detecting multiple lung cancer mutation genes at one time, and the primer probe composition is assembled into a kit, comprises EGFR, ALK, ROS1 and MET genes, covers 26 gene mutations and 26 gene fusion, and is used for detecting multiple lung cancer mutation genes. The detection result is high in sensitivity, strong in specificity, good in repeatability and simple, convenient and rapid to operate, and a rapid and reliable detection method is provided for clinic.

Provided is a method for treating ALK-positive non-small cell lung cancer in a subject by means of administering a compound A or a pharmaceutically acceptable salt thereof to the subject. Further provided is a method for treating ROS1-positive non-small cell lung cancer in a subject by means of administering compound A or a pharmaceutically acceptable salt thereof to the subject.

This invention discloses a macrocyclic compound with multi-target degradation activities of TRK, ROS1, and ALK, its preparation method, and its pharmaceutical uses. The general structural formula of the macrocyclic compound with multi-target degradation activities of TRK, ROS1, and ALK is: [Insert structural formula here]. This invention also specifically discloses the preparation method of this macrocyclic compound and its use in the preparation of drugs for treating various cancers or coronavirus infections. The macrocyclic compound prepared by this invention simultaneously possesses multi-target degradation activities of TRK, ROS1, and ALK, and can serve as a multi-target degrader for TRK, ROS1, and ALK proteins, and can be used to treat various cancers or coronavirus infections.

This invention belongs to the field of biomedical technology, specifically relating to the application of crizotinib in inducing tolerant dendritic cells (tDCs). This invention provides the application of crizotinib in inducing tolerant dendritic cells. This invention discovers that crizotinib can act as a highly effective inducer of tDCs, significantly inhibiting the activated state of DCs, suppressing their maturation function, reducing their immunostimulatory capacity, and thus inhibiting T cell activation, thereby exerting a therapeutic effect in immune diseases such as GVHD. The inhibitory effects of crizotinib on DCs in this invention include reducing the expression of maturation markers CD80, CD40, and CD86. The crizotinib used in this invention is an FDA-approved ALK / ROS1 inhibitor, primarily used for the treatment of non-small cell lung cancer. This invention discovers its application in immunotherapy, realizing the repurposing of an existing drug, and has significant economic value.

The application discloses a primer composition and a reagent for fusion gene detection, and can detect human lung cancer fusion genes based on a multiplex PCR method. The primer composition can specifically amplify at least 50 fusion mutation forms of five fusion driver genes, such as ALK, NRG, NTRK1, RET and ROS1, in an RNA sample through sequences shown in SEQ ID NO 1-54, and can serve as a housekeeping gene for sample quality control. The reaction can be carried out in one tube or can be split into multiple tubes for carrying out. In the multiple tube reaction, a specific probe composition modified with a fluorescent group and having sequences shown in SEQ ID NO 55-70 can be added to form a qPCR reagent. When the qPCR reagent is used to detect a positive sample, the fusion gene in 0.04 ng of RNA can be reported. The process of the application is simple, efficient, easy to operate and low in cost, and has a good prospect.

A compound of formula (I) or a tautomer, a stereoisomer, a solvate, a nitrogen oxide, a prodrug, an isotope derivative or a pharmaceutically acceptable salt thereof exhibit kinase inhibitory activity against a variety of kinases (such as TRK, ALK and ROS1) and mutants thereof, in particular TRK and a mutant form thereof. An in vitro cell inhibitory activity test and an in vivo anti-tumor model test show that the compounds have a strong inhibitory effect on a variety of cells containing TRK mutations and tumors, have a good safety, and have a good clinical value as drugs.

The present application relates to the field of C12Q1 / 6851, and more particularly, the present application relates to a primer probe combination, a kit and a method for detecting human ALK and ROS1 gene fusion. The primer probe combination comprises at least a primer probe combination A which specifically detects at least one EML4-ALK fusion gene; a primer probe combination B which specifically detects at least one ROS1 fusion gene; and a primer probe combination C which specifically detects an internal reference gene. The primer probe combination and the detection method of the present application have high specificity and sensitivity, improve the signal-to-noise ratio, have good resolution and accuracy, and have excellent linear relationship, so that the result can be easily judged.