madrid2i

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The present invention refers to inhibitors of the S100 calcium- binding protein A9 (S100A9)/S100A8 – Toll Like Receptor 4(TLR4) dimer-receptor axis for use in the treatment of Heart Failure with preserved Ejection Fraction (HFpEF). The present invention further refers to pharmaceutical formulations comprising the said inhibitors. The present invention's use of compounds and pharmaceutical formulations may be advantageously employed in HFpEF by attenuating the deleterious effect on endothelial function and prevention of inflammation, production of reactive oxygen species, apoptosis, senescence and pro-fibrotic phenotype.

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CLAIMS 1. Inhibitors of the S100 calcium-binding protein A9 (S100A9) /S100A8 - Toll Like Receptor 4 (TLR4) dimer-receptor axis for use in the treatment of heart failure with preserved ejection fraction (HFpEF) , through attenuating the deleterious effect of EVs on endothelial function and prevention of a pro-fibrotic phenotype. 2. Use according to claim 1 wherein the said inhibitors comprise Resatorvid (TAK-242, CLI095) ; Eritoran; Dutasteride (DB01126) ; Buclizine (DB00354) ; Conivaptan (DB00872) ; Lomitapide (DB08827) ; Adapalene (DB00210) ; Lumacaftor (DB09280) ; Dihydroergotamine (DB00320) ; Bromocriptine (DB01200) ; Tolvaptan (DB06212) Nandrolone phenpropionate (DB00984) ; Flunarizine (DB04841) ; Irinotecan (DB00762) ; Dihydrotachysterol (DB01070) ; Antrafenine (DB01419) ; Nilotinib (DB04868) ; Medrogestone (DB09124) ; Itraconazole (DB01167) ; Doxercalci f erol (DB06410) ; Ponatinib (DB08901) ; Netupitant (DB09048) ; Difenoxin (DB01501) ; Paricalcitol (DB00910) ; Pimozide (DB01100) ; Tasosartan (DB01349) ; Alfacalcidol (DB01436) ; Fluspirilene (DB04842) ; Azilsartan medoxomil (DB08822) ; Cabozantinib (DB08875) ; Lorpiprazole (DB09195) Ergocalciferol (DB00153) ; Loperamide (DB00836) ; Drospirenone (DB01395) Pranlukast (DB01411) ; Ziprasidone (DB00246) ; Meclizine (DB00737) ; Sertindole (DB06144) ; Lurasidone (DB08815) ; Vorapaxar (DB09030) ; Umeclidinium (DB09076) , as well as S100A9 Inhibitors, such as ABR-238901; Tasquinimod (ABR-215050 ) ; Paquinimod (ABR 25757) ; laquinimod (ABR-215062 ) ; Roquinimex (ABR212626) ; Azeliragon; FPS-ZM1; RAGE 229; AC-73; antagonist peptide-9 (AP9) and combinations thereof . 3. Pharmaceutical formulation for use for use in the treatment of HFpEF characterized by comprising inhibitors of the S100A9/S100A8-TLR4 dimer-receptor axis. 4. Pharmaceutical formulation according to claim 3 wherein the said inhibitors comprise Resatorvid (TAK-242, CLI095) ; Eritoran; Dutasteride (DB01126) ; Buclizine (DB00354) ; Conivaptan (DB00872) ; Lomitapide (DB08827) ; Adapalene (DB00210) ; Lumacaftor (DB09280) ; Dihydroergotamine (DB00320) ; Bromocriptine (DB01200) ; Tolvaptan (DB06212) Nandrolone phenpropionate (DB00984) ; Flunarizine (DB04841) ; Irinotecan (DB00762) ; Dihydrotachysterol (DB01070) ; Antrafenine (DB01419) ; Nilotinib (DB04868) ; Medrogestone (DB09124) ; Itraconazole (DB01167) ; Doxercalcif erol (DB06410) ; Ponatinib (DB08901) ; Netupitant (DB09048) ; Difenoxin (DB01501) ; Paricalcitol (DB00910) ; Pimozide (DB01100) ; Tasosartan (DB01349) ; Alfacalcidol (DB01436) ; Fluspirilene (DB04842) ; Azilsartan medoxomil (DB08822) ; Cabozantinib (DB08875) ; Lorpiprazole (DB09195) Ergocalciferol (DB00153) ; Loperamide (DB00836) ; Drospirenone (DB01395) Pranlukast (DB01411) ; Ziprasidone (DB00246) ; Meclizine (DB00737) ; Sertindole (DB06144) ; Lurasidone (DB08815) ; Vorapaxar (DB09030) ; Umeclidinium (DB09076) ; ABR- 238901; Tasquinimod (ABR-215050) ; Paquinimod (ABR 25757) ; laquinimod (ABR-215062 ) ; Roquinimex (ABR212626) , Azeliragon; FPS-ZM1; RAGE 229; AC-73; antagonist peptide-9 (AP9) and combinations thereof. Lisbon, 6<th>December 2024

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