38 results about "Reversible inhibition" patented technology

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R0, L and R1 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, e.g., in the treatment of a disease that is treatable by administration of a DPP1 inhibitor.

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R0, L and R1 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, e.g., in the treatment of a disease that is treatable by administration of a DPP1 inhibitor.

The application discloses a covalent polypeptide inhibitor targeting protein kinase A, a conjugate, a kit, a pharmaceutical composition and application. The general formula of the covalent polypeptide inhibitor is Z1-Seq-Z2; wherein Seq is an amino acid sequence; the C-terminal of Seq comprises a pseudo-substrate recognition motif recognized by protein kinase A, a non-natural amino acid with a covalent reaction group, and can be covalently crosslinked with a Cys200 residue on a catalytic subunit of protein kinase A; Z1 is selected from hydrogen, an acyl group, a fluorescent group, biotin, an isotopic tag or a biological ortho-reaction group; and Z2 is selected from a hydroxyl group, an amino group, a cell-penetrating peptide or a stabilization modification group. The covalent polypeptide inhibitor can strongly and irreversibly inhibit PKA activity, and can be used as an active probe to specifically label active PKA in a complex biological sample, and is used for biological research and drug development.

The present invention relates to therapeutic combinations of an irreversible BTK inhibitor and a macrocyclic reversible BTK inhibitor and a method for treating a subject having a hyperproliferative disease, in particular a B-cell hematological malignancy, which subject receives or has received a Bruton's tyrosine kinase (BTK) inhibitor for treatment of the hyperproliferative disease, using said therapeutic combinations. The present invention further relates to method treating a subject diagnosed with or at risk of a recurrent or refractory form of a hyperproliferative disease, in particular a B-cell hematological malignancy, which subject has previously been treated with an irreversible BTK inhibitor, using said therapeutic combinations. In particular embodiments the method comprises: a) monitoring the patient over the course of therapy to determine whether the subject has a C481 mutation in BTK and b) co-administering to the patient an irreversible and a macrocyclic reversible BTK inhibitor if the patient has a C481 mutation in BTK. The invention further relates to a method for treating a subject having a hyperproliferative disease, in particular a B-cell hematological malignancy, wherein the treatment comprises administering said therapeutic combinations.

The invention relates to the technical field of geological reinforcement, and discloses a grout stopping method for stratum pre-grouting reinforcement, which adopts an A and B double-component grout system: the B component contains thermal stability urease inhibited by a reversible inhibitor; the component A contains a corresponding inhibitor and a corresponding scavenger, and the two components are mixed to release the reaction through inhibition, so that the controllable prolonging of the slurry gelation time is realized, and the blockage of a pipeline is avoided. A self-indication and slow-release carrier loaded with copper ions is arranged in the component A, after the slurry reaction is started, ammonium ions of a reaction product replace the copper ions, the blue change of the slurry is caused, and a visual basis is provided for judging the injection stopping opportunity. The component A further comprises an energy field response medium and reserve urea packaged in the carrier, and the energy field response medium and the reserve urea enable the consolidation body to have the later non-contact remote control enhancement capacity and the micro-crack passive self-repairing capacity respectively. The grouting process is safe and controllable, the reaction state is visible in real time, and the performance of the consolidated body is regulated and controlled in the later period.

Provided are pharmaceutical compositions for treating cancer patients. The pharmaceutical compositions include a combination of compounds inhibiting PTP1 b activity and chemotherapeutic agents. The PTP 1 b inhibitors in such pharmaceutical compositions can include a small molecule such as an anti-sense inhibitor, an allosteric / reversible inhibitor, and / or a permanent / chemical modification inhibitor. Methods of treating subjects are also provided. Such treatment methods include administering to a subject in need of treatment a pharmaceutical composition including one or more compounds inhibiting PTP1b activity and one or more chemotherapeutic agents. Also provided herein are methods of restoring an anti-tumor immune response in a subject receiving chemotherapy, including administering to the subject a PTP 1 b inhibitor prior to, during and / or after receiving a chemotherapeutic agent, whereby an anti-tumor immune response in the subject is restored and / or enhanced.

A fluorescent probe for detecting cytochrome oxidase CYP2D6 and its application, which belong to the field of biomedicine technology. The specific probe substrate can be used to determine the enzyme activity of CYP2D6 in biological systems. The process of CYP2D6 enzyme activity determination is as follows: the benzylmethoxy demethylation reaction in the meso-position pyridinium quaternary ammonium salt of Bodipy compounds is selected as the probe reaction, and the activity of CYP2D6 enzyme in various biological samples is determined by quantitatively detecting the amount of its metabolite generated per unit time. The probe is a selective probe for detecting CYP2D6 activity, which can achieve efficient discovery of CYP2D6 inhibitors (including mechanism-type inhibitors) and in-depth research on CYP2D6-related diseases. The probe can also be used for rapid in vitro screening of reversible and irreversible inhibitors, activators and inducers of CYP2D6, and for detecting drug-drug interactions of CYP2D6 at the in vivo level.

The present invention relates to therapeutic combinations of an irreversible BTK inhibitor and a reversible BTK inhibitor and relates to a method for treating a subject having a hyperproliferative disease, in particular a B-cell hematological malignancy, which subject receives or has received a Bruton's tyrosine kinase (BTK) inhibitor for treatment of the hyperproliferative disease, using said therapeutic combinations. The present invention further relates to method treating a subject diagnosed with or at risk of a recurrent or refractory form of a hyperproliferative disease, in particular a B-cell hematological malignancy, which subject has previously been treated with an irreversible BTK inhibitor, using said therapeutic combinations. In particular embodiments the method comprises: a) monitoring the patient over the course of therapy to determine whether the subject has a C481 mutation in BTK and b) co-administering to the patient an irreversible and a reversible BTK inhibitor if the patient has a C481 mutation in BTK. The invention further relates to a method for treating a subject having a hyperproliferative disease, in particular a B-cell hematological malignancy, wherein the treatment comprises administering said therapeutic combinations.

The present invention relates to a medical use of a macrocyclic reversible BTK inhibitor and relates to a macrocyclic reversible BTK inhibitor for use in a method for treating a subject having a hyperproliferative disease. In particular embodiments, the subject receives or has received a Bruton's tyrosine kinase (BTK) inhibitor, preferably an irreversible BTK inhibitor, for treatment of the hyperproliferative disease. In particular embodiments, the method comprises a step of monitoring the subject over the course of therapy to determine whether the subject has a mutation in an endogenous gene encoding BTK.

Provided herein are compounds of formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, wherein R 0 、 L and R 1 is defined herein. Also provided herein are pharmaceutical compositions comprising the compound of formula (I) or a pharmaceutically acceptable salt or deuterated form thereof, and methods of using the compound of formula (I) or a pharmaceutically acceptable salt or deuterated form thereof, for example, in the treatment of diseases treatable by administration of a DPP1 inhibitor. [Formula 1] JPEG2026503035000405.jpg27123

Described herein are aptamers for temperature-dependent reversible inhibition of thermostable polymerase activity in order to improve sensitivity and specificity of various reactions and assays involving hot start polynucleotide synthesis. Methods for use of the aptamers and related compositions and kits are also provided.

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R0 , L and R1 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, e.g., in the treatment of a disease that is treatable by administration of a DPP1 inhibitor.

Described herein are methods and compositions for improved polymerase chain reaction (PCR). In one aspect the methods and compositions include improved aptamers to reversibly inhibit polymerase and exonuclease activity of the polymerase enzyme.

The present disclosure relates to aptamers for temperature-dependent reversible inhibition of thermostable polymerase activity in order to improve sensitivity and specificity of various reactions and assays involving hot start polynucleotide synthesis. Methods for use of the aptamers and related compositions and kits are also provided.

The present disclosure relates to aptamers for temperature-dependent reversible inhibition of thermostable polymerase activity in order to improve sensitivity and specificity of various reactions and assays involving hot start polynucleotide synthesis. Methods for use of the aptamers and related compositions and kits are also provided.

The invention is applicable to the technical field of bioengineering, and provides a method for protecting an in-vitro acute gout cell model based on a polyphenol compound. According to the method, the process for ultrasonic extraction of the polyphenol compounds in the inonotus obliquus is optimized, and the optimal conditions are that the material-liquid ratio is 1: 40 g / mL, the ultrasonic time is 30 min, the ultrasonic power is 280 W, and the predicted extraction rate value is 0.866% and is verified to be 0.888%. Polyphenolic compounds (protocatechuic acid, protocatechualdehyde and osmundone) have concentration-dependent inhibition on xanthine oxidase, the ability sequence is osmundone > protocatechualdehyde > protocatechuic acid, the inhibition is reversible, and the inhibition types are competitive, miscible and miscible. Under the safe concentration, ROS, NO and LDH in acute gout model cells induced by MSU can be reduced, the activity of SOD is improved, it is prompted that inonotus obliquus has the potential hyperuricemia resisting effect, and a basis is provided for industrial production of polyphenol of inonotus obliquus.

The present invention relates to fused imidazo pyridine compounds, and pharmaceutically acceptable compositions thereof, useful as BTK inhibitors.

Aromatic six-membered ring-fused imidazole derivatives, their preparation methods and applications belong to the field of pharmaceutical synthesis, and specifically relate to aromatic six-membered ring-fused imidazole derivatives represented by general formula (I), their preparation methods, and their application as LSD1 inhibitors. The compounds provided by the present invention exhibit good activity at the in vitro enzyme level. Different from the existing irreversible inhibitors with an anti-phenylcyclopropylamine parent nucleus structure, the present invention provides new skeleton compounds for the field of LSD1 inhibitor research. The raw materials used in the synthetic route adopted by the present invention are cheap and easily available, the reagents used are common reagents, the reaction conditions are mild, the post-treatment is simple, and the compounds of this type can be efficiently prepared. The compounds provided by the present invention can be used alone or in combination as lysine-specific demethylase-1 inhibitors for the treatment of various tumor diseases.

The present invention relates to a compound of general formula (1) and a preparation method therefor, and use of the compound of formula (1) and isomers, crystalline forms and pharmaceutically acceptable salts thereof as an irreversible inhibitor for a K-Ras G12C mutant protein in preparing a medicament for resisting Ras-related diseases such as tumors.

The present invention provides an irreversible HDAC6 subtype selective inhibitor, a preparation method thereof and an application thereof. The irreversible HDAC6 subtype selective inhibitor of the present invention has a structure shown in the following formula (I). The inhibitor of the present invention has good selectivity and inhibitory activity for HDAC6, can effectively achieve selective inhibition of the HDAC6 subtype at a relatively low concentration, and at the same time can avoid the toxic and side effects caused by inhibiting other HDAC subtypes, and has high safety. The inhibitor of the present invention has an irreversible inhibitory effect on HDAC6 and has a long-lasting drug effect.

To provide a cost-effective method of preparing next generation antibody therapeutics with high molecular weights that allows creation of diverse libraries of antibody-like drugs with altered valences, geometries, effector functions and stoichiometry simply by combinations of a comparatively small number of building blocks.SOLUTION: One aspect of the disclosure provides constructs comprising a first fusion protein, a second fusion protein, and a linker. The first fusion protein and the second fusion protein each include an affinity reagent and a reactive enzyme. The linker includes a first functional group specific for irreversibly inhibiting the first fusion protein reactive enzyme at a first terminus, and a second functional group specific for irreversibly inhibiting the second fusion protein reactive enzyme at a second terminus.SELECTED DRAWING: None

The application discloses a preparation method of a high-glycuroninoglycan content fucoidan degradation product and application thereof. The specific preparation method is as follows: after fucoidan powder is treated by hot air assisted radio frequency drying, the fucoidan degradation product is obtained by acid hydrolysis combined with a two-step sedimentation method, the average molecular weight of the fucoidan degradation product is 7-9 kDa, the monosaccharide components are fucose, xylose, mannose, galactose, rhamnose, glucuronic acid and galacturonic acid, and the molar proportion of glycuroninoglycan is higher than 50%. The fucoidan degradation product provided by the application can effectively reduce the activities of alpha-amylase and alpha-glucosidase through reversible inhibition, and can effectively reduce the postprandial blood glucose level of mice in animal experiments. The fucoidan degradation product provided by the application has a good prospect in the field of developing blood glucose lowering food.

The invention discloses a preparation method and application of a high-uronic-acid-content fucoidin degradation product, and the specific preparation method is as follows: fucoidin powder subjected to hot air assisted radio frequency drying treatment is subjected to acid hydrolysis and two-step sedimentation to obtain the fucoidin degradation product, the average molecular weight is 7-9kDa, monosaccharide components are fucose, xylose and mannose, and the fucoidin degradation product has the advantages of high uronic-acid-content fucoidin degradation product and high-uronic-acid-content fucoidin degradation product and high-uronic-acid-content fucoidin degradation product. Galactose, rhamnose, glucuronic acid and galacturonic acid, and the molar ratio of the glucuronic acid is higher than 50%. The fucoidin degradation product provided by the invention can effectively reduce the activity of alpha-amylase and alpha-glucosidase through reversible inhibition, can effectively reduce the postprandial blood sugar level of mice in animal experiments, and has a good prospect in the field of development of blood sugar reducing foods.

The invention discloses a double-aromatic heterocyclic compound and application thereof. The compound has good inhibitory activity on FGFR, can be used as a receptor tyrosine kinase inhibitor, and especially can be used as a fibroblast growth factor receptor (FGFR) kinase irreversible inhibitor. Therefore, the compound provided by the invention can be used for preparing medicines for treating clinical diseases related to FGFR, such as medicines for preventing and / or treating diseases related to FGFR-related cell abnormal proliferation, morphological change, hyperkinesia and the like in a living body and medicines for diseases related to angiogenesis or cancerometastasis.

This invention discloses BacPROTACs targeting dihydropteranoic acid synthase, their preparation method, and their applications, belonging to the fields of medicinal chemistry and anti-infective drug technology. The BacPROTACs have the structure shown in Formula I, II, or III, and are composed of a DHPS inhibitor fragment, a linker group, and a phosphorylated arginine (pArg) fragment. The pArg fragment, as a functional group capable of interacting with the bacterial ClpCP protease system, is coupled to a DHPS inhibitor through linkers of different types and chain lengths, resulting in bifunctional molecules possessing both DHPS binding and ClpCP recruitment capabilities. These compounds can recruit the ClpCP protease system while binding to DHPS, thereby inducing or promoting DHPS degradation, reducing target protein levels, and expanding the pharmacodynamic mechanism of DHPS-targeted drugs. Compared with existing DHPS inhibitors that mainly rely on reversible inhibition, this invention provides a new technical solution for the development of antibacterial drugs through a design strategy combining inhibition and targeted degradation. These compounds can be used to prepare antibacterial drugs.

The application discloses a quinazoline derivative containing a spiro ring. Specifically, the application relates to a compound shown in a general formula (1) and a preparation method of the compound, and application of the compound shown in the general formula (1) and each isomer, each crystal form, a pharmaceutically acceptable salt, a hydrate or a solvate of the compound as an irreversible inhibitor of G12C mutant K-Ras protein in preparation of a drug for resisting a tumor and other Ras-related diseases.

A fused bicyclic compound having an effect in inhibition of the activity of a tyrosine kinase, and preparation and use thereof are disclosed. In particular, a compound of formula (IV) or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a hydrate, a polymorph, a prodrug or an isotopic variation thereof, as well as a pharmaceutical composition including the same are disclosed. As a selective irreversible inhibitor of Bruton's tyrosine kinase, the described compound can be used for preventing or treating diseases such as inflammation, autoimmune diseases (such as rheumatoid arthritis), xenogeneic immune diseases and cancers.

The present invention relates to a compound of general formula (1a) or general formula (1b) and a method for preparing the same, and use of the compound of general formula (1a) or general formula (1b) and an isomer, a crystalline form, a pharmaceutically acceptable salt, a hydrate or a solvate thereof as an irreversible inhibitor for an IDH mutant in preparing a medicament for resisting a diseases such as a tumor related to an IDH mutant protein.