13 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.

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.

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 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.

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.

The invention belongs to the technical field of biological medicines, and relates to application of a histone deacetylase inhibitor HDACi in preparation of a medicine for preventing and / or treating hyperammonemia-induced encephalopathy. According to the invention, a histone deacetylase inhibitor HDACi is used as a new medicine, the HDACi can enter a central nervous system, and the GS is triggered to be degraded through a proteasome mediated by CRBN E3 ubiquitin ligase by improving the acetylation level of a key enzyme, namely glutamine synthetase (GS), of astrocytes, so that the GS protein abundance is reversibly reduced, and the GS protein abundance is reduced. The application has the advantages that pathological accumulation of toxic metabolite glutamine can be reduced from the source, cerebral edema, autophagy-lysosomal dysfunction, neuroinflammation and neuron injury caused by the pathological accumulation can be synchronously improved, severe neurotoxicity such as persistent enzyme inhibition and acute epilepsy caused by irreversible inhibitors such as MSO can be avoided, clinical transformation risks can be obviously reduced, and the safety is high.

The invention discloses a targeting covalent activation prodrug compound and a preparation method and application thereof, the targeting covalent activation prodrug compound is named as Ibt-DOX, and the structural formula of the targeting covalent activation prodrug compound is shown in the specification. According to the invention, high affinity and irreversible inhibition capability of a classical targeting covalent inhibitor to Bruton's tyrosine kinase (BTK) are retained, and in-situ release of potent chemotherapeutic drugs is triggered by a targeting covalent binding process, so that high synergy of targeting covalent inhibition and local chemotherapy is realized; the direct killing capacity of the medicine on BTK high-expression B cell tumor cells is greatly improved, and the treatment effect of the medicine is obviously better than that of the medicine which is independently used or is simply combined with chemotherapy medicine.

The invention relates to the technical field of molecular calculation and DNA nanotechnology, in particular to a molecular signal rollback method and system based on cutting enzyme assistance. According to the method, the nicking enzyme is introduced as a rollback factor, and the problem that a traditional molecular sequential circuit enters an irreversible inhibition state due to abnormal input is solved. When a target DNA substrate is combined and inactivated by an inhibition signal, a nicking enzyme capable of specifically recognizing the inhibition compound is added, the inhibition signal is dissociated through a cutting effect, so that the substrate is recovered to an initial active state, then an activation signal can be responded again, output is triggered, and rollback from an abnormal silence state to a normal functional state is realized. The invention further provides a specified rollback module capable of performing fixed-point recovery on the specific abnormal path under multiple instruction input. The reliability and controllability of a molecular information processing system are remarkably enhanced, and a foundation is laid for constructing a complex and robust molecular calculation and diagnosis system.