The present invention relates to aminothiolesters compounds for use for modulating the immune response in a subject. In particular, said compounds are comprised in a lipidic nanocapsule. The invention further relates to a pharmaceutical composition and to combination products comprising at least one aminothiolester compound and an immune checkpoint inhibitor, and their use for the treatment of cancer.
A61K 31/265 - Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/4402 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
A61K 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present invention relates to novel aminoesters compounds or its pharmaceutically acceptable salts or optical isomers, racemates, diastereoisomers, enantiomers or tautomers. The present invention also relates to their process of preparation and to these compounds for use as a medicament, in particular for the treatment or the prevention of cancer. The present invention further relates to an antibody drug conjugate comprising such compounds.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 31/265 - Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
A61K 31/4402 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
A61K 31/4406 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 31/27 - Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, e.g. meprobamate, carbachol, neostigmine
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
The present invention relates to aminotiolesters compounds for use for modulating the immune response in a subject. In particular, said compounds are comprised in a lipidic nanocapsule. The invention further relates to a pharmaceutical composition and to combination products comprising at least one aminothiolester compound and an immune checkpoint inhibitor, and their use for the treatment of cancer.
A61K 31/265 - Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
A61K 31/4453 - Non-condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
The present invention relates to novel aminoesters compounds or its pharmaceutically acceptable salts or optical isomers, racemates, diastereoisomers, enantiomers or tautomers. The present invention also relates to their process of preparation and to these compounds for use as a medicament, in particular for the treatment or the prevention of cancer. The present invention further relates to an antibody drug conjugate comprising such compounds.
C07D 213/34 - Sulfur atoms to which a second hetero atom is attached
A61K 31/4402 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
A61K 31/4406 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
C07D 213/59 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with at least one of the bonds being to sulfur
C07C 327/22 - Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
A61K 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
A61K 31/255 - Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
The invention relates to a specific substrate on an ALDH isoenzyme, to a composition comprising at least one such substrate, to a diagnostic marker comprising such a substrate, and to the uses thereof and associated methods.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
C12Q 1/32 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase involving dehydrogenase
6.
Monoclonal antibody specific for gamma-glutamyl-l-epsilon-lysine for the monitoring of apoptosis
The present invention concerns an ex vivo method for the monitoring of apoptosis which is based on the detection of free gamma-glutamyl-L-epsilon-Lysine (GGEL) in a biological sample of a subject with a monoclonal antibody specific to GGEL. The invention also relates to the monoclonal antibody specific to GGEL, as well as to diagnostic kits containing such a ligand.
2; d) reacting the compound obtained in step c) with an alkyl chloroformate, a reagent capable of forming, with the compound obtained in step c), an acid halide, or a reagent capable of forming, with the compound obtained in step c), a mixed anhydride; e) reacting the compound obtained in step d) with an SMe anion precursor compound.
C07C 327/30 - Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
8.
Combination comprising an aminothiolester compound or a pharmaceutically acceptable salt thereof and a compound able to increase the H2O2 level in cancer cells of a subject
A61K 31/145 - Amines, e.g. amantadine having sulfur atoms, e.g. thiurams (N—C(S)—S—C(S)—N or N—C(S)—S—S—C(S)—N)Sulfinylamines (—N=SO)Sulfonylamines (—N=SO2)
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
A61K 31/4453 - Non-condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (France)
UNIVERSITÉ CLAUDE BERNARD LYON 1 (France)
Inventor
Ceylan, Ismail
Martin, Guillaume
Quash, Gérard
Perez-Alea, Milleidys
Fournet, Guy
Abstract
The invention relates to a specific substrate of an ALDH isoenzyme, to a composition comprising at least one such substrate, to a diagnostic marker comprising such a substrate, and to the uses thereof and associated methods.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
C12Q 1/32 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase involving dehydrogenase
C12N 9/04 - Oxidoreductases (1.), e.g. luciferase acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
G01N 33/533 - Production of labelled immunochemicals with fluorescent label
10.
MONOCLONAL ANTIBODY SPECIFIC FOR GAMMA-GLUTAMYL-L-EPSILON-LYSINE FOR THE MONITORING OF APOPTOSIS
The present invention concerns an ex vivo method for the monitoring of apoptosis which is based on the detection of free gamma-glutamyl-L-epsilon-Lysine (GGEL) in a biological sample of a subject with a monoclonal antibody specific to GGEL. The invention also relates to the monoclonal antibody specific to GGEL, as well as to diagnostic kits containing such a ligand.
A process for preparing aminothiol ester compounds and salts thereof. The present invention relates to a process for preparing compounds of formula (I), (I) comprising the following steps: a) reacting a compound of formula (II) with an inorganic acid or an organic acid, (II) b) reacting the compound obtained in step a) with a base; c) reacting the compound obtained in step b) with CO2 ; d) reacting the compound obtained in step c) with an alkyl chloroformate, a reagent capable of forming, with the compound obtained in step c), an acid halide, or a reagent capable of forming, with the compound obtained in step c), a mixed anhydride; e) reacting the compound obtained in step d) with an SMe anion precursor compound.
C07C 327/22 - Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
12.
AMINOTHIOLESTER COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, FOR USE IN THE TREATMENT OF CANCER
The present invention relates to the treatment of cancer in a subject, wherein cancer cells of said subject overproduce H 2 0 2 and have a level of GSH below 0,5 nmol for 25 000 cells, with aminothiolester compounds or pharmaceutically acceptable salts thereof, in particular with S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, more particularly with 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate. It also relates to a method for selecting a subject suffering from a cancer and who will most likely benefit from a treatment with aminothiolester compounds or pharmaceutically acceptable salts thereof, in particular with S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, more particularly with 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate.
A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
A61K 31/4453 - Non-condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
13.
COMBINATION COMPRISING AN AMINOTHIOLESTER COMPOUND OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND A COMPOUND ABLE TO INCREASE THE H2O2 LEVEL IN CANCER CELLS OF A SUBJECT
Combination comprising an aminothiolester compound or a pharmaceutically acceptable salt thereof and a compound able to increase the H 2 0 2 level in cancer cells of a subject, for use as a medicament The present invention relates to a combination comprising an aminothiolester compound or a pharmaceutically acceptable salt thereof, in particular the S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, and more particularly the 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate, and a compound able to increase H 2 0 2 level in cancer cells of a subject, in particular for use for the treatment of cancer in a subject, wherein cancer cells of said subject do not overproduce H 2 0 2 in comparison to a control value and have a level of GSH below 5 nmol for 25000 cells.
A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
A61K 31/4453 - Non-condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
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