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1. (WO2018130679) METHODS AND PHARMACEUTICAL COMPOSITIONS FOR REDUCING CD95- MEDIATED CELL MOTILITY
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Pub. No.: WO/2018/130679 International Application No.: PCT/EP2018/050820
Publication Date: 19.07.2018 International Filing Date: 15.01.2018
IPC:
A61K 31/427 (2006.01) ,A61K 31/125 (2006.01) ,A61K 31/4439 (2006.01) ,A61K 31/603 (2006.01) ,A61K 31/704 (2006.01) ,A61P 35/00 (2006.01) ,A61P 29/00 (2006.01) ,A61P 37/00 (2006.01) ,A61P 35/02 (2006.01)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
33
Heterocyclic compounds
395
having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
41
having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
425
Thiazoles
427
not condensed and containing further heterocyclic rings
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
12
Ketones
122
having the oxygen atom directly attached to a ring, e.g. quinones, vitamin K1, anthralin
125
Camphor; Nuclear substituted derivatives thereof
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
33
Heterocyclic compounds
395
having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
435
having six-membered rings with one nitrogen as the only ring hetero atom
44
Non-condensed pyridines; Hydrogenated derivatives thereof
4427
containing further heterocyclic ring systems
4439
containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
60
Salicylic acid; Derivatives thereof
603
having further aromatic rings, e.g. diflunisal
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
70
Carbohydrates; Sugars; Derivatives thereof
7028
Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
7034
attached to a carbocyclic compound, e.g. phloridzin
704
attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29
Non-central analgesic, antipyretic or antiinflammatory agents, e.g antirheumatic agents; Non-steroidal antiinflammatory drugs (NSAIDs)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37
Drugs for immunological or allergic disorders
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
02
specific for leukemia
Applicants:
INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR/FR]; 101, rue de Tolbiac 75013 Paris, FR
UNIVERSITÉ DE RENNES 1 [FR/FR]; 2, rue du Thabor 35000 Rennes, FR
UNIVERSITÉ DE BORDEAUX [FR/FR]; 35 Place Pey Berland 33000 BORDEAUX, FR
INSTITUT BERGONIÉ [FR/FR]; 229 cours de l'Argonne 33000 Bordeaux, FR
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) [FR/FR]; 3, rue Michel-Ange 75016 Paris, FR
CHU DE BORDEAUX [FR/FR]; 12, rue Dubernat 33400 Talence, FR
Inventors:
LEGEMBRE, Patrick; FR
VACHER, Pierre; FR
POISSONNIER, Amanda; FR
BLANCO, Patrick; FR
Agent:
COLLIN, Matthieu; FR
Priority Data:
17305047.716.01.2017EP
17305665.606.06.2017EP
17306432.020.10.2017EP
Title (EN) METHODS AND PHARMACEUTICAL COMPOSITIONS FOR REDUCING CD95- MEDIATED CELL MOTILITY
(FR) PROCÉDÉS ET COMPOSITIONS PHARMACEUTIQUES POUR RÉDUIRE LA MOTILITÉ CELLULAIRE MÉDIÉE PAR CD95
Abstract:
(EN) The present invention relates to a method for reducing CD95-mediated cell motility. To identify chemicals disrupting CD95/PLCγ1 interaction, the inventors screened a chemical library of EMA/FDA-approved molecules against a protein-fragment complementation assay (PCA) monitoring the binding of CD95 to PLCγ1. From this screen, five chemical molecules showed the ability to disrupt CD95/PLCγ1 interaction and to neutralize the CD95-mediated calcium signaling pathway and cell migration in human peripheral blood lymphocytes (PBLs) and Th17 cells. Thus, the present invention relates to a method for reducing CD95-mediated cell motility, comprising administering the subject with at least one compound selected from the group consisting of HIV-protease inhibitors (e.g. ritonavir), diflunisal, anethole, rosiglitazone and daunorubicin. Particularly, the method of the invention find use in the treatment of cancer such as triple negative breast cancer, autoimmune inflammatory disease such as systemic lupus erythematosus, inflammatory condition and Th17-mediated disease.
(FR) La présente invention concerne un procédé de réduction de la motilité cellulaire médiée par CD95. Pour identifier des substances chimiques perturbant l'interaction CD95/PLCγ1, les inventeurs ont criblé une bibliothèque chimique de molécules approuvées par EMA/FDA vis-à-vis d'un dosage de complémentation protéines-fragments (PCA) surveillant la liaison de CD95 à PLCγ1. A partir de ce criblage, cinq molécules chimiques ont montré la capacité de perturber l'interaction CD95/PLCγ1 et de neutraliser la voie de signalisation calcique médiée par CD95 et la migration cellulaire dans les lymphocytes sanguins périphériques (LSP) humains et les cellules Th17. Ainsi, la présente invention concerne un procédé de réduction de la motilité cellulaire médiée par CD95, comprenant l'administration au sujet d'au moins un composé choisi dans le groupe constitué par les inhibiteurs de la protéase du VIH (par exemple le ritonavir), le diflunisal, l’anéthol, la rosiglitazone et la daunorubicine. En particulier, le procédé de l'invention trouve une utilisation dans le traitement du cancer tel qu'un cancer du sein triple négatif, une maladie inflammatoire auto-immune telle qu'un lupus érythémateux disséminé, une affection inflammatoire et une maladie médiée par Th17.
Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)