57 results about "ROS1" patented technology

A compound suitable for treating cancer, in particular NSCLC, inhibits activity of oncogenic ROS1 kinase and ALK kinase. The compound has certain structural components such as a quinoline moiety in the backbone and at least one phenyl-containing moiety in a side chain with a hydrophobic substituent attached to the backbone via an up to 6-membered linking group as well as a further hydrophobic moiety. The presence of the structural components allows for an advantageous interaction with the ROS1 kinase domain and, further, with the ALK kinase domain. Hence, said compound represents a highly promising opportunity for patients bearing ROS1- or ALK-dependent cancer. A composition, in particular a pharmaceutical composition, includes the compound. A method for targeting cancer cells harboring an abnormality in ROS1 gene or ALK gene includes contacting a cell with the compound.

The invention discloses a compound shown in formula I, wherein all symbols are defined as Claims. The compound shown in Formula I has good inhibitory activity to ALK, ROS1 and/or TRK kinase, can be used for preparing a drug inhibiting the ALK, ROS1 and/or TRK kinase and can be used for treating cancers, pains, nerve diseases, autoimmune diseases or inflammations. (The formula 1 is described in thespecification).

The invention discloses a detection chip for a tumor driving gene and application thereof. The detection chip for the tumor driving gene comprises an ALK (anaplastic lymphoma kinase) fusion detection agent, an EGFR (epidermal growth factor receptor) fusion detection agent, an RET (reticulocyte) fusion detection agent and an ROS1 (reactive oxygen species 1) fusion detection agent. Proofed by the results of clinical detect, after fusion probes corresponding to the ALK, the EGFR, the RET and the ROS1 are specifically designed, the detection chip has the advantages that the sensitivity is high, and the gene fusion between a particular site area of the ALK, the EGFR, the RET and the ROS1 and fusion segments is specifically detected. The invention further discloses a detection chip for detecting a second sequence group of the gene mutation and a third sequence group of the gene amplification; after detecting once, the gene fusion, gene mutation and gene amplification of the multiple tumor driving genes, such as the ALK, BRAF (aserine/theroninespecific kinases), DDR2 (discordin domain receptor 2), the EGFR, ERBB2 (receptor tyrosine kinase 2), FGFR1 (fibroblast growth factor receptor 1), KRAS (kirstenrat sarcoma viral oncogene), MET (methionine), NRAS, PIK3CA (phosphatidylino-sitol 3-kinases), the RET and the ROS1.

The invention discloses a standard product for detecting genes of clinical medications for lung cancer and an application thereof, wherein the standard product comprises a lowest-detection-limit reference product at least comprising two different levels of variation-frequency DNA mixtures; and each level of variation-frequency DNA mixture comprises the following mutation sites: EGFR gene G719S, E746_A750del, S768I, T790M and L858R mutation sites, EML4-ALK gene E6, E20 and E13, E20 mutation site, SLC34A2-ROS1 gene E4, and E32 mutation site. By application of the technical scheme disclosed by the invention, whether a kit can detect the gene mutation and the gene frequency can be judged according to results, the accuracy of detection results of the existing kit can be verified and more accurate guidance also can be provided for clinical medications.

The invention discloses a primer, a probe and an assay kit for detecting v-ros avian UR2 sarcoma viral oncogene homolog 1 (ROS1) gene fusion mutation, wherein the primer and the probe comprises the following sequences of SEQ ID NO 1 to SEQ ID NO 8. A specific primer and probe technique is adopted, and can specifically detect the human ROS1 gene fusion mutation. The method has the advantages that (1) a real-time fluorescent polymerase chain reaction (PCR) system is built to simultaneously detect four types of ROS1 gene fusion mutation; (2) the sensitivity is high, the mutation of 10-20kb can be detected; (3) the method is simple to operate and low in detection, and has a wide clinical application scope; (4) the sample detection scope is wide, and the sample can be fresh pathological tissues and paraffine-embedded tissues; and (5) the detection speed is fast, and the detection process can be completed within 90 minutes.

The invention discloses a kit for quantitatively detecting ALK, RET and ROS1 fusion genes based on ddPCR. The kit comprises a negative reference substance, a positive reference substance, a PCR reaction solution I and a PCR reaction solution II. The invention provides an RT-PCR quantitative detection system based on ddPCR. The RT-PCR quantitative detection system comprises a forward primer, a reverse primer and a fluorescent probe, wherein the forward primer and the reverse primer aim at fusion genes EML4-ALK, CCDC6-RET and CD74-ROS1 and an internal control gene TBP. According to the kit, a forward primer is designed on a 5'partner gene, a probe and a reverse primer are designed on a 3'driver gene to detect ALK, RET and ROS1 fusion genes, and a detection result is expressed by a copy number in unit volume. Through adoption of a ddPCR detection method, whether EML4-ALK, CCDC6-RET and CD74-ROS1 fusion occurs in a clinical sample can be simply and rapidly detected, an important basis is provided for diagnosis, typing, clinical treatment and prognosis of ALK, RET and ROS1 related tumor diseases, and a new thought is provided for clinical treatment.

The invention discloses a method for constructing a lung cancer multi-gene mutation library. The method can realize mutation of 1435 somatic cells of human genes EGFR, K-ras, B-raf, N-ras, PIK3CA, c-MET, TP53, c-Kit, PDGFRA, ALK, ROS1, RET, ERBB2, NTRK1 and NTRK3. The method can individually manage multiple target sequences and fast finish library construction. The whole library construction process is finished in 2-3h and the manual operation time is only 45min. The method can be used for Illumina and Ion torrent platforms. Through combination of the method and a high-throughput sequencing platform, the problem that a small amount of paraffin tissue slices and peripheral blood samples of a lung cancer patient need multi-gene and multi-target detection of somatic cells is solved and a costis low.

The present invention relates to a cancer kit containing a monoclonal antibody of specific binding ROS1. The monoclonal antibody is obtained by taking an ROS1 kinase domain obtained by screening as anantigen and immunizing a mouse. The antibody has the relatively good binding specificity, and it is verified that the antibody has the function of inhibiting the growth of tumor cells, so that the kit has the relatively good application prospect.

The invention relates to a method for detecting whether fusion mutation of target gene occurs, a primer combination, a kit and an application thereof. A plurality of primers are sequentially designedaccording to the possible gene fusion occurrence direction by the primer design method of the invention, forming a primer combination, wherein the primers of the primer combination extend along the direction in which gene fusion occurs, can carry out directional enrichment on the target gene in which unknown fusion occurs, overcomes the disadvantage that the existing amplicon sequencing method cannot enrich the unknown fusion gene targetedly, and is conducive to the discovery and detection of the unknown fusion type of the gene; At the same time, the interval between two adjacent primers is about 0 - 130 bp, which is good for highly fragmented samples (such as cfDNA, FFPE samples). The invention also designs primer combinations for detecting fusion mutations of lung cancer genes (includingALK gene, NTRK1 gene, RET gene, ROS1 gene, FGFR3 gene and NTRK3 gene), After multiple rounds of detection and optimization of the primer sequence, the homogeneity of the sequencing data was more than85%, and the capture efficiency was more than 92%. Finally, the effective detection of unknown fusion mutation of various lung cancer genes was successfully achieved.

The invention discloses a kit and a detection method for abnormity of ROS1 and C-met genes. The kit includes a first group of probes and a second group of probes, which aim to the ROS1 gene, and/or a third group of probes and a fourth group of probes, which aim to the C-met gene. Each group of probes is labeled with a fluorescent dye, wherein the color of the fluorescent dye on the probes in the same group is same while the colors of the fluorescent dyes on the probes in different groups are different. The four groups of probes respectively are amplification products by amplifying a primer with corresponding BAC cloning as a template. The FISH probes are produced through repeated comparison and selection and then utilization of optimized BAC cloning as the template and through amplification by designing a primer aiming to a non-repeated and highly-conserved sequence, so that the kit has excellent specificity and lower background noise. The kit can achieve the optimal balance between detection specificity and hybridization time length, so that not only are specificity and sensitivity of a result ensured, but also hybridization time is reduced, thereby increasing detection efficiency.

The present invention discloses a primer composition and a reagent for fusion gene detection. A human lung cancer fusion gene can be detected based on a multiplex PCR method. The primer composition can specifically amplify at least 50 fusion mutation forms of five fusion driving genes such as ALK, NRG, NTRK1, RET and ROS1 in an RNA sample through sequences as shown in SEQ ID NO:1-54, and can be used as a house-keeping gene for sample quality control. A reaction can be carried out in one tube, and can also be carried out in multiple tubes. During the multi-tube reaction, a specific probe composition modified with a fluorophore and having sequences as shown in SEQ ID NO 55-70 can be added to form the qPCR reagent. When the qPCR reagent is used for detecting a positive sample, the fusion genein 0.04 ng RNA can be reported. The process is simple and efficient, and the reagent is easy to operate and low in cost, and has a good prospect.

The invention relates to a 2,4-diarylaminopyrimidine derivative shown as a general formula I and optical isomers thereof, pharmaceutically acceptable salts, solvates or prodrugs, as well as preparation methods thereof and a pharmaceutical composition taking the compound of the general formula I as an active ingredient. In the formula, substituent groups R1, R2, R3, R4, R5, R6 and X have meanings given in the description. The invention further relates to a compound of the general formula I with strong ALK and ROS1 kinase inhibition effects, and further relates to application of the compounds and optical isomers and pharmaceutically acceptable salts thereof in preparation of medicines for treating and/or preventing diseases caused by abnormal expressions of ALK and ROS1, particularly application in preparation of medicines for treating and/or preventing cancers. The structural formula is as shown in the description.

The invention relates to the technical field of digital PCR, and in particular relates to a primer pair, probe and kit for quickly detecting ROS1 gene fusion mutation and a use method thereof. A primer pair and probe for detecting ROS1 gene fusion mutation are included; the primer pair and the probe are designed according to a target area to be detected; according to the primer pair and the probe,a kit for rapidly detecting ROS1 gene fusion mutation is provided; the kit comprises the primer pair and the probe; and a use method of the primer pair, the probe or the kit is included. The method comprises the following steps of: S1, extracting to obtain a tumour tissue RNA sample; S2, performing digital PCR reaction on an RNA sample by using the primer pair, the probe or the kit; and S3, judging whether ROS1 gene fusion mutation occurs in the sample or not. The method disclosed by the invention is not affected by fusion partners and fusion sites; gene fusion causing ROS1 gene transcriptionabnormality can be accurately found; known and unknown fusion variations are detected at the same time; false negative is avoided; experimental operation is simple; the detection period is short; andthe cost performance is high.

The invention discloses lung cancer targeted drug and chemotherapy drug genomes and an application thereof in lung cancer clinical drug treatment. The targeted drug genome comprises AKT1, ALK, BRAF, CCND1, CDKN2A, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, HRAS, IGF1R, KDR, KIT, KRAS, MAP2K1, MET, NF1, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RET, ROS1, STK11 and TP53; and the chemotherapy drug genome comprises ABCB1, CDA, CEP72, CYP1B1, CYP2C8, DPYD, ERCC1, ERCC2, GSTM, GSTP1, MTHFR, RRM1, SLCO1B1, TEKT4, TPMT, TYMS, UMPS, XPC and XRCC1. The lung cancer targeted drug and chemotherapy drug genomes disclosed by the invention are applied to guidance of clinical precise chemotherapy of the lung cancer or auxiliary diagnosis of the lung cancer and curative effect and after-healingmonitoring, can provide the most effective drug selection for lung cancer patients with drug resistance or toxic and side effect intolerance caused by conventional drugs and targeted and chemotherapydrug requirements, improve the drug treatment effect, and reduce the toxic and side effects of the drugs.

The invention discloses a detection method for detecting lung cancer gene fusion based on a NanoString platform. The method comprises the following steps: 1, collecting gene fusion information and determining a housekeeping gene; 2, designing a probe; 3, establishing a positive threshold calculation model and judging a positive result; most fusion types related to current lung cancer targeted therapy are collected, upstream and downstream sequences at each gene fusion breakpoint are determined, and a probe is designed based on an elementary method. The fusion with other lung cancer related to detection based on a NanoString platform is more comprehensive, especially in the fusion aspect of the four genes of MET and NTRK1/2/3; the mode of detecting whether fusion occurs or not by detecting whether the 5'end and the 3 'end of the ROS1 gene are unbalanced or not is a problem all the time, the detection sensitivity is very low, a threshold value is very difficult to judge, the algorithm is optimized again, and a new positive judgment standard is determined.

The invention provides a method and a kit for constructing a multi-gene mutation sequencing library of lung cancer driving genes. According to primers for amplifying the lung cancer driving genes, amplification products of the primers cover hotspot mutation sites and gene fusion types of the multiple lung cancer driving genes such as EGFR, ALK, ROS1, KRAS, BRAF, PIK3CA, HER2, RET, MET, NRAS, NTRK1-3 and MAP2K1, and aiming at the NTRK1-3 gene fusion, no second-generation sequencing library covering the fusion type exists in China at present. The primers of the kit provided by the invention can effectively capture the multi-gene sequences of the lung cancer driving genes, and the multi-gene mutation sequencing library of the lung cancer driving genes can be constructed only by two-step PCR amplification and purification with a multiplex PCR method, so that the amplification and detection of NTRK1-3 gene fusion are realized for the first time.

A method for isolated a protein complex comprising BCL10 and at least one, preferably all, of ROS1, LSD1, BTK, KU80, KU70, CUL4A, IMP3, thioredoxin, hTID1, DAP3, CDK1/CDC2, PRL1/PTP4A1 or NM23. Methods for using this complex to diagnose or prognose diseases including diabetes, obesity, cancer, neurodegenerative disease or inflammatory diseases associated with activation of NF-κB Methods for distinguishing lean, obese and diabetic subjects based on expression of BCL10 and its ligands are also disclosed. The invention also pertains to pharmaceutical compositions comprising ligands for BCL10 or other components of this complex or agents such as siRNA or miRNA that regulate the expression of the protein components of this complex.