29 results about "Polymerase inhibitor" patented technology

Provided in the present application are an antibody-drug conjugate, and a preparation method therefor and the use thereof. The antibody-drug conjugate has a structure as represented by the following formula (III) or formula (IV). The drug is selected from a DNA topoisomerase inhibitor, a DNA intercalator, an RNA polymerase inhibitor, and a PARP inhibitor. The prepared antibody-drug conjugate exhibits a relatively good drug-to-antibody ratio and good targeted killing effects on breast cancer, gastric cancer, and lung cancer (e.g., non-small cell lung cancer, specifically lung adenocarcinoma).

The present invention relates to compounds of formula (I):and methods useful for inhibiting the DNA polymerase IIIC enzyme. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of Gram-positive bacterial infections.

The present disclosure is directed to compositions comprising POLQ inhibitor Compounds of Formula (I), methods of preparing the forgoing, combinations of the forgoing with DNA PK inhibitors as well as methods of use for said compositions.

The present invention relates to a stable pharmaceutical composition comprising a phthalazinone derivative having excellent activity as a poly(ADP-ribose) polymerase inhibitor.

The present application provides a DNA polymerase theta (Pol theta) inhibitor represented by structural formula (I) and its enantiomers, diastereomers, racemates, tautomers, stereoisomers, geometric isomers, deuterium compounds, nitroxides, metabolites or pharmaceutically acceptable salts, esters, solvates, hydrates, isotopically labeled compounds or prodrugs thereof, and corresponding preparation methods and applications. Biological experiments show that the compound of the present application has a Pol theta inhibitory effect, and can be used alone or in combination to treat tumors with high incidence of homologous recombination deficiency (HRD) or DNA damage response (DDR) deficiency.

The invention discloses a nucleoside compound and application thereof, and mainly relates to a nucleoside compound as shown in a formula (I) or various prodrugs, stereoisomers, pharmaceutically acceptable salts and racemic compounds of the nucleoside compound, a pharmaceutical composition containing the formula (I) and application of the nucleoside compound or the prodrugs, the stereoisomers, the pharmaceutically acceptable salts and the racemic compounds in preparation of drugs for preventing and / or treating RNA virus infection. Furthermore, the compound disclosed by the invention has remarkable broad-spectrum anti-RNA virus activity, overcomes the instability of a raw medicine in water, has a good patent medicine prospect and good oral bioavailability, and can be used for preparing a medicine of a virus RNA dependent RNA polymerase inhibitor or a medicine composition containing the medicine and the like.

This invention relates to a novel compound of formula (I), said compound being a DNA polymerase θ (Polθ) inhibitor; and also to pharmaceutical salts thereof, isotope labels thereof, solvates thereof, stereoisomers or tautomers thereof, pharmaceutical compositions thereof, methods thereof for preparation thereof, and therapeutic uses thereof.

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.

The present application discloses specific compounds of Formula (I) and their use in therapy, in particular, their use as Polymerase Theta (Polθ) inhibitors for the treatment of cancer. The application further discloses the use of a combination comprising a compound of Formula (I) and a radiotherapy or a radioligand in therapy, in particular, the use of specific compounds of Formula (I) as a Polymerase Theta (Polθ) inhibitor in combination with a radiotherapy or a radioligand for the treatment of cancer.

The present invention relates to compounds of Formula I and pharmaceutically salts thereof, wherein ring A, R1, R2, R3, integer a, integer b, X4, X5, X6 and X7 are each as defined herein. The compounds of the present invention inhibit Pol [theta]. Thus, the novel therapeutic compounds are useful in the treatment and / or prevention of diseases and conditions associated with Pol [theta] activity, such as, but not limited to, the treatment and / or prevention of cancer. The invention also relates to pharmaceutical compositions comprising the novel therapeutic compounds as defined herein, methods of synthesizing these compounds and their use for treating diseases and / or conditions associated with Pol [theta] activity.

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.

This invention relates to the use of small molecule compounds that allosterically inhibit ALC1 (CHD1L), particularly two classes of ALC1 (CHD1L) allosteric inhibitors of formulas (I) and (II). When combined with inhibitors of several classes of cancer drugs, namely topoisomerase I, topoisomerase II, ATM, ATR, Wee1, BRD, and MEK, or when combined with mitomycin C, paclitaxel, ionizing radiation, or antibody-drug conjugates having tumor-specific antibodies conjugated to TOP1 inhibitors, the small molecule compounds and the allosteric inhibitors exhibit enhancing, preferably additive, effects in the treatment of proliferative diseases. Furthermore, this invention relates to the ALC1 inhibitor of formula (II), which, when combined with PARP inhibitors (poly(ADP-ribose)-polymerase inhibitors (PARPi)), exhibit synergistic effects in the treatment of pancreatic cancer or fallopian tube cancer. By synergizing with the functions of the aforementioned cancer drugs, the ALC1 inhibitors, particularly those of formulas (I) and (II) that enhance the cancer cell killing properties of the aforementioned cancer drugs, are particularly capable of achieving treatments in which any of the aforementioned inhibitors have already been used as part of standard care.

Disclosed herein are substituted isomeric naphthyridinyl benzamides and related compounds as broad-spectrum GHP-class polymerase inhibitors, and pharmaceutical compositions thereof, utilized for the treatment and prevention of viral infections. The inventive compounds may be used to treat a paramyxovirus infection, an orthoparamyxovirus infection, a respirovirus infection, a morbillivirus infection, or a henipavirus infection.

The invention relates to the technical field of derivatives with anti-tumor activity, in particular to a photoactivatable derivative with anti-tumor activity and a preparation method of the photoactivatable derivative. Comprise stereoisomers, tautomers, nitrogen oxides, deuterated compounds, hydrates, solvates, metabolites, prodrugs, pharmaceutically acceptable salts or co-crystals. The light-activated mitochondrial RNA polymerase inhibitor, especially the POLRMT inhibitor, is prepared for the first time, can treat diseases related to the inhibitor and various tumor diseases, has a good effect, and has relatively high cancer cell proliferation resistance activity and safety.

A method of amplifying a target nucleic acid in a DNA sample comprising (a) contacting the DNA sample containing the target nucleic acid with a DNA polymerase, at least two oligonucleotide primers designed to flank the target nucleic acid, a mixture of dATP, dGTP, dCTP, and dTTP, and a conjugate comprising a DNA polymerase inhibitor covalently attached to a negative temperature sensitive polymer, (b) heating the output of step (a) to a temperature at which the conjugate precipitates and thus the DNA polymerase is no longer inhibited and (c) amplifying the target nucleic acid, e.g. by performing PCR steps of denaturing the target nucleic acid, annealing the primers to the target nucleic acid, and extending the primers, wherein step (c) is repeated at least two times. Also provided is a conjugate comprising a DNA polymerase inhibitor covalently attached to a negative temperature sensitive polymer and kits and aqueous compositions comprising the same.

Disclosed herein are compounds of Formula (I):that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and / or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

The present disclosure is directed to compositions comprising POLQ inhibitor Compounds of Formula (I), methods of preparing the forgoing, combinations of the forgoing with DNA PK inhibitos as well as methods of use for said compositions.

The present disclosure relates to novel compounds as polymerase theta inhibitor.

The invention relates to combined application of an antibody drug conjugate and a polyadenosine diphosphate ribose polymerase inhibitor. The invention relates to an antibody drug conjugate, in particular to combined application of the antibody drug conjugate, a polyadenosine diphosphate ribose polymerase inhibitor, an anti-VEGF antibody and a chemotherapeutic drug. Specifically, the invention provides an application of the antibody drug conjugate or pharmaceutically acceptable salt, metabolite or solvate single drug thereof, or a combination of the antibody drug conjugate and one or more of a polyadenosine diphosphate ribose polymerase inhibitor, an anti-VEGF antibody and a chemotherapeutic drug in preparation of drugs for preventing and / or treating cancers.

Provided herein are nick translation signal (NTS) assays and methods of use thereof for identifying subjects with tumors with functional deficits akin to those in BRCA1 or BRCA2 mutations, who are candidates for treatment with a treatment designed to induce cell death by direct or indirect DNA damage, e.g., poly(ADP-ribose) polymerase inhibitors (PARPi) in mono and combination therapies.

The present application relates to viral entry inhibitors and RNA polymerase inhibitors, pharmaceutical compositions comprising one or more of the same, and combination therapies, as well as methods of making and of using the foregoing in the treatment of certain diseases.

Disclosed herein are compounds of Formula (I) that inhibit DNA polymerase theta (Pol θ) activity, particularly by inhibiting the activity of the ATP-dependent helicase domain of Pol θ. Also disclosed are pharmaceutical compositions containing such compounds and methods for treating and / or preventing diseases treatable by inhibiting Pol θ, such as cancers, including homologous recombination (HR)-deficient cancers. [C1] JPEG2025541823000057.jpg36170

Disclosed are methods of decreasing lagging strand synthesis comprising interfering with or altering DNA polymerase α (DNA polα) or primase activity. Disclosed are methods of reprogramming a progenitor cell comprising administering a DNA polα inhibitor or primase inhibitor to the progenitor cell, thereby reprogramming the progenitor cell to form a reprogrammed progenitor cell. Disclosed are methods of reducing DNA polα and / or primase levels or activity in a cell comprising contacting a cell with a DNA polα inhibitor and / or primase inhibitor. Disclosed are methods of altering chromatin in a progenitor cell comprising contacting a progenitor cell with a DNA polα inhibitor and / or a primase inhibitor to the cell. Disclosed are methods of increasing fertility of a subject comprising administering a therapeutically effective amount of a DNA polα inhibitor and / or a primase inhibitor to the subject. Disclosed are methods of increasing reproductive lifespan of a subject comprising administering a therapeutically effective amount of a DNA polα inhibitor and / or a primase inhibitor to the subject.

Disclosed herein are compositions and methods relating to the inhibitors of the translesion synthesis (TLS) pathway, including methods of preventing or treating RNA viruses and prolonged symptoms (for example, long COVID).

Disclosed herein are compounds of Formula (I):that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and / or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

Methods for treating gliomas, such as glioblastoma, including administering an aromatase inhibitor, such as letrozole, to a subject suffering from a glioma. The method may further include administering the aromatase inhibitor in combination with a poly-ADP ribose polymerase inhibitor, such as olaparib, pamiparib, veliparib or niraparib.

Provided are methods and formulations for the treatment of p53-deficient cancers using a combinational drug strategy which enhances DNA damage in p53 deficient cells while not allowing cells to escape cell death by activation of p53-p21 signaling. Wild-type p53 carriers, on the other hand, respond with activation of p53-p21 signaling and cell-cycle arrest, thereby escaping cell death. The methods involve administering to an individual in need of treatment a combination of one or more poly (ADP ribose) polymerase inhibitors (PARPi) and one or more deoxyuridine analogs. Pharmaceutical formulations comprising PARPi and dU analogs are also provided.

The invention relates to a preparation method of a poly (adenosine diphosphate-ribose) polymerase inhibitor intermediate, and the method comprises the following steps: firstly, removing an acetyl protecting group by CH3OLi to prepare a compound H-1, and then hydrolyzing methyl ester by LiOH to obtain a compound Y. Compared with a traditional process method, the method has the advantages that the yield is high, and the yield is high. The step-by-step hydrolysis method can greatly reduce and eliminate byproducts generated in the reaction, and the content of the byproducts is from gt; the reaction temperature is reduced to 1% or below from 10%, and the total reaction yield is improved.

The disclosure, in one aspect, relates to methods for treating cancer in a subject, the methods including at least the steps of administering at least one drug from each of at least two classes selected from an inhibitor of poly-ADP ribose polymerase (PARP inhibitor), an inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs inhibitor), an inhibitor of wild-type isocitrate dehydrogenase (IDH inhibitor), an inhibitor of histone acetyltransferase (HAT inhibitor), an inhibitor of histone deacetylase (HDAC inhibitor), an inhibitor of DNA polymerase Θ (POLΘ inhibitor), an inhibitor of platelet-derived growth factor receptor (PDGFR inhibitor), and a DNA alkylating agent to the subject. In any of these aspects, the disclosed method allows for administering lower doses of the drugs in combination compared to administration as single drugs while preventing the recurrence of the cancer, preventing drug resistance of the cancer, and reducing side effects associated with cancer treatment.