Abstract: A benzimidazole compound and a preparation method thereof. Various substituted benzimidazoles are synthesized by a SN2 reaction and a cyclization reaction. Namely, o-fluorinated aryl-N,N-dimethyl-formamidine and primary amine are subjected to an cyclization by a one-pot reaction, wherein a fluorine atom is substituted by an amino, and then dimethylamine is eliminated, thus forming the product. The method does not require the use of any metal catalyst and/or any toxic reagent, and has a specific selectivity. No isomer exists in the reaction product.

Abstract: Compositions for preventing or treating virus infections inhibit the biogenesis of cytoplasmic viral assembly compartment (cVAC). The preferred compounds are dihydroquinazolinones.

Abstract: A tyrosine kinase inhibitor (TKI) for use in a method for the treatment of cancer in a patient, wherein the method comprises subjecting the patient to reduced caloric intake, i.e a daily caloric intake reduced by 10-100%, including starvation, for a period of 24-190 hours and administering the tyrosine kinase inhibitor to the patient during such period; the tyrosine kinase inhibitor is preferably selected among Lapatinib, Crizotinib, Gefitinib, Erlotinib, Afatinib and Regorafenib.

Abstract: Methods of inhibiting S. aureus propagation, and screening for compounds that inhibit S. aureus propagation, are described. A method of inhibiting S. aureus propagation comprises either inhibiting or stabilizing ribosomal binding of a specific S. aureus tRNA in the S. aureus by an amount sufficient to inhibit S. aureus protein expression. A method of screening for compounds useful for inhibiting S. aureus propagation comprises contacting a specific S. aureus tRNA to a ribosome that binds that tRNA in the presence of the test compound and an mRNA that codes for methionine and arginine (i.e., includes the sequence AUGAGA), and then determining whether the compound inhibits the binding of that tRNA.

Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the ?-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

Abstract: The present invention relates to the novel solid forms of Afatinib monomaleate and preparation methods thereof; the solid forms of Afatinib monomaleate of the present invention have many improved properties as compared to the known crystalline form of Afatinib salt; and the present invention also relates to pharmaceutical compositions containing the novel solid forms of Afatinib monomaleate as well as the uses thereof for treating terminal non-small cell lung cancer (NSCLS) and HER2 positive advanced breast cancer.

Abstract: The present disclosure encompasses crystalline forms of Afatininb di-maleate and methods of their use.

Abstract: The present invention relates to a method for treating a Chlamydiae infection comprising the administration of a therapeutically effective amount of a compound of formula (I) to a subject in need thereof: Wherein, R1, R2, R3, R4 and p are as defined in claim 1.

Abstract: A class of quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof with novel structures is provided; meanwhile, a pharmaceutical composition comprising a pharmaceutically effective amount of said quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof, and pharmaceutically acceptable excipients or additives is also provided. By modifying and transforming the quinazoline and screening of the transformed compounds on the activity of tyrosine kinase inhibition, most of the compounds have been found to possess inhibitory activity against one or several of EGFR, VEGFR-2, c-erbB-2, c-erbB-4, c-met, tie-2, PDGFR, c-src, lck, Zap70 and fyn kinases. The present invention has the advantages of reasonable design, broad source of and easy access to the raw materials, simple and easy operation of the preparation methods, mild reaction conditions, high yield of the products and being beneficial for industrial-scale production.

Abstract: The present invention relates to quinazolinedione derivatives represented by formula (I) or pharmaceutically acceptable salts thereof.

Abstract: The present invention is directed to novel bicyclic compounds, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are useful for the treatment of protein kinases mediated diseases and conditions. Novel bicyclic compounds disclosed herein include quinazolines and quinolines.

Abstract: The present invention is directed to novel quinazolines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

Abstract: Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.

Abstract: Described herein are inhibitors of FGFR-4, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions.

Abstract: Described herein are compounds, pharmaceutical compositions and methods for treating a respiratory syncytial virus infection in a subject, or for inhibiting replication of respiratory syncytial virus.

Abstract: Provided herein are methods comprising providing a tyrosine derivative and a solid particulate material (and, optionally, melanin) and applying force to said tyrosine derivative and said solid particulate material for a time and under conditions effective to impregnate at least one of said tyrosine derivative and said solid particulate material with the other of said tyrosine derivative and said solid particulate material. The invention also provides compositions comprising at least one of a tyrosine derivative impregnated with a solid particulate material and a solid particulate material impregnated with a tyrosine derivative.

Abstract: Afatinib salts and crystalline forms thereof are described in the present application and processes for their preparation. Crystalline forms of Afatinib are also described in the present application and processes for their preparation. The present invention also includes pharmaceutical compositions of such Afatinib salts and crystalline forms thereof or crystalline forms of Afatinib, methods of their preparation and the use thereof in the treatment of a patient in need thereof.

Abstract: The invention relates to combinations comprising an HDAC inhibitor and a Her2 inhibitor for the treatrent of breast cancer in a subject in need thereof. The invention also relates to combinations comprising an HDAC inhibitor and a PI3K inhibitor for the treatment of breast cancer in a subject in need thereof. Also provided herein are methods for treating breast cancer in a subject in need thereof comprising administering to the subject an effective amount of one of the above combinations. Further provided are methods for inhibiting migration and/or invasion of a breast cancer cell in a subject by administering to the subject a HDAC6 specific inhibitor.

Abstract: The present invention provides methods of predicting response to a cancer therapy based on the methylation status of the ERBB2 gene. One aspect of the invention provides a method of predicting response to an EGFR inhibitor therapy based on the methylation status of the ERBB2 gene.

Abstract: Compounds having the formula (I) wherein R1, R2, R3 and Ar as defined herein are inhibitors of ERK kinase. Also disclosed are compositions and methods for treating hyperproliferative disorders.

Abstract: The present invention provides compositions and methods of use in the treatment/prevention of chlamydial infection and/or diseases and disorders associated with chlamydial infection in a subject.

Abstract: A class of quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof with novel structures is provided; meanwhile, a pharmaceutical composition comprising a pharmaceutically effective amount of said quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof, and pharmaceutically acceptable excipients or additives is also provided. By modifying and transforming the quinazoline and screening of the transformed compounds on the activity of tyrosine kinase inhibition, most of the compounds have been found to possess inhibitory activity against one or several of EGFR, VEGFR-2, c-erbB-2, c-erbB-4, c-met, tie-2, PDGFR, c-src, lck, Zap70 and fyn kinases. The present invention has the advantages of reasonable design, broad source of and easy access to the raw materials, simple and easy operation of the preparation methods, mild reaction conditions, high yield of the products and being beneficial for industrial-scale production.

Abstract: Embodiments of the present disclosure, in one aspect, relate to a 2,4-diaminoquinazoline compound, pharmaceutical compositions including a 2,4-diaminoquinazoline compound, methods of treatment of a condition (e.g., infection) or disease, methods of treatment using compositions or pharmaceutical compositions, and the like.

Abstract: The present invention relates to a method of treating cancer in a human and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine, or a pharmaceutically acceptable hydrate and/or salt thereof, and N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide, or a pharmaceutically acceptable salt thereof, to a human in need thereof.

Abstract: The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.

Abstract: A pharmaceutical formulation comprising the compound of formula

Abstract: Disclosed herein are compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein X1, L, Rx, Ry, G, Z, A, m, n, and p are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

Abstract: The present disclosure provides methods of that include detecting in a biological sample from a patient having or suspected of having cancer the presence of a polypeptide having ROS1 kinase activity or a polynucleotide encoding the same and detecting in the biological sample the presence of a mutant EGFR polypeptide or a polynucleotide encoding the same. In some aspects, the disclosure provides methods of treating a patient for cancer that include determining that a biological sample from a tumor in the patient includes a polypeptide having ROS1 kinase activity or a polynucleotide encoding the same and a mutant EGFR polypeptide or a polynucleotide encoding the same and administering to the patient a therapeutically effective amount of a ROS1 inhibitor and an EGFR inhibitor, thereby treating the patient for cancer.

Abstract: [PROBLEMS] To identify mutations that can serve as indicators for predicting the effectiveness of drug treatments in cancers such as lung cancer; to provide a means for detecting said mutations; and to provide a means for identifying, based on said mutations, patients with cancer or subjects with a risk of cancer, in which drugs targeting genes having said mutations or proteins encoded by said genes show a therapeutic effect. [MEANS FOR SOLVING] A method for detecting a gene fusion serving as a responsible mutation (driver mutation) for cancer, the method comprising the step of detecting any one of an EZR-ERBB4 fusion polynucleotide, a KIAA1468-RET fusion polynucleotide, a TRIM24-a BRAF fusion polynucleotide, a CD74-NRG1 fusion polynucleotide, and an SLC3A2-NRG1 fusion polynucleotide, or a polypeptide encoded thereby, in an isolated sample from a subject with cancer.

Abstract: The present invention provides novel substituted pyrazolone compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

Abstract: The present invention provides novel substituted pyrazolone compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

Abstract: Provided herein are thiophene compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders, including but not limited to, psychosis and schizophrenia.

Abstract: The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase ? and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.

Abstract: Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed.

Abstract: Methods are provided for treating cancer in a patient in need thereof with a HER2 inhibitor, where such patients have certain polymorphisms in VEGFA, VEGFR or IGF1R.

Abstract: The present invention relates to gene regulation. In particular, the present invention provides small compounds capable of modulating ESX-mediated transcription and related methods of therapeutic and research use. In addition, the present invention provides methods for treating conditions associated with aberrant EGFR expression with ESX-mediated transcription modulators (e.g., ESX-mediated transcription inhibitors).

Abstract: Impurities of lapatinib such as N-{3-chloro-4-[(2-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine compound of formula (I) or a salt thereof: and analytical methods for identifying and quantifying such impurities of Lapatinib and salts thereof are provided. Also provided is Lapatinib containing less than about 0.05 percent of this and related impurities and methods for preparing such pure forms of Lapatinib.

Abstract: This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

Abstract: The present invention relates to the field of methods for providing components of pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to methods for providing stable, amorphous hybrid nanoparticles, comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component, useful in pharmaceutical compositions.

Abstract: An antitumor effect potentiator of another antitumor agent, including an acylthiourea compound represented by formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient: wherein R1 represents a C1-6 alkyl group which may have a substituent, while the substituent represents any one of a hydroxyl group, a C3-10 cycloalkyl group, a C1-6 alkoxy group which may have a substituent, a C1-6 alkylamino group which may have a substituent, a C1-6 alkanoylamino group, a C1-6 alkylsulfonyl group, a C6-14 aromatic hydrocarbon group which may have a substituent, a saturated or unsaturated heterocyclic group which may have a substituent, a C1-6 alkylaminocarbonyl group which may have a substituent, a saturated or unsaturated heterocyclic carbonyl group which may have a substituent; R2 represents a fluorine atom or a chlorine atom; and R3 represents a hydrogen atom, a fluorine atom, or a chlorine atom.

Abstract: The present invention relates to the field of methods for providing pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to compositions comprising stable, amorphous hybrid nanoparticles, comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component, useful in pharmaceutical compositions and in therapy.

Abstract: A method of treating a ductal carcinoma in situ (DCIS) lesion in a subject in need thereof is disclosed. The method comprises administering to the subject a therapeutically effective amount of a first agent capable of down-regulating activity and/or expression of at least one component participating in a NOTCH pathway, and a second agent capable of down-regulating an activity and/or expression of HER2, thereby treating the DCIS lesion.

Abstract: This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I wherein Ar, R1 and R2 are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

Abstract: Provided herein are compounds and methods of synthesis thereof. The compounds set forth herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, neurodegenerative disorders, neuropsychiatric disorders, disorders of cognition, learning or memory, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds set forth herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

Abstract: Methods of treating subjects with cancer and screening for MDM2 inhibitors that may be effective cancer therapeutics are provided herein. The cancers that may be treated using MDM2 inhibitors using the methods described herein include those that are or may become resistant to treatment with tyrosine kinase inhibitors. Methods of treating subjects with cancers that have, or develop in response to treatment with tyrosine kinase inhibitors, elevated levels of MDM2, Mcl-1 or PP5 or decreased levels of Huwe1 or CAS using MDM2 inhibitors are provided herein. The MDM2 inhibitors may be effective at treating these cancers alone or in combination with a tyrosine kinase inhibitor regardless of p53 status (mutant or wild-type) of the cancer.

Abstract: Oral pharmaceutical formulations containing ditosylate salts of 4-quinazolineamines are described as well as methods of using the same in the treatment of disorders characterized by aberrant erbB family PTK activity.

Abstract: Provided is a method of treating or preventing age-related macular degeneration (AMD) in a patient subject to, or symptomatic of the disease, wherein the method comprises restoring normal lysosomal pH (pHL), or acidifying an abnormally elevated pHL, thus decreasing or preventing a damaging accumulation of lipofuscin or waste products in the retinal pigment epithelium (RPE) cells of the eye of the patient. Further, this method is achieved by modulating the action of the P2X7 and/or P2Y12 receptors of the RPE cells, specifically decreasing the acidity (pHL) of the RPE lysosomes by administering selected receptor antagonists affecting the action of the P2X7 and/or P2Y12 receptors of the RPE. Methods for selecting and quantifying the effectiveness of drugs to restore pHL and determine outer segment clearance rates is also provided using a high through-put screening protocol.

Abstract: The present invention provides analogs and derivatives of thalidomide which inhibit cancer and angiogenesis. The present invention further provides compounds which disrupt microtubule polymerization. The present further provides methods of treating cancers comprising mutant p53.

Abstract: The present invention relates to a method of treatment of patients suffering from cancer and harboring mutations of EGFR in the tumor, for instance an activating mutation of the EGFR or a mutation responsible for resistance or the emergence of acquired resistance to treatment with reversible EGFR and/or HER2 inhibitors or irreversible inhibitors such as CI-1033, EKB-569, HKI-272 or HKI-357, comprising administering an effective amount of the irreversible EGFR inhibitor BIBW2992 (1) 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, to a person in need of such treatment, optionally in combination with the administration of a further chemotherapeutic agent, in combination with radiotherapy, radio-immunotherapy and/or tumor resection by surgery, and to the use of a BIBW 2992 (1) for preparing a pharmaceutical composition for the treatment of patients suffering from cancer and harboring mutations of EGFR in the tumor.

Abstract: Embodiments of the present disclosure relate to methods and compositions for treating a subject with ovarian cancer. Some embodiments include treating a subject with a particular combination of chemotherapeutic agents.