CA2884607A1 - Therapeutic compositions including acrylamido compounds or phenyl-substiituted maleimide compounds and uses thereof to treat and prevent mitochondrial diseases and conditions - Google Patents
Therapeutic compositions including acrylamido compounds or phenyl-substiituted maleimide compounds and uses thereof to treat and prevent mitochondrial diseases and conditions Download PDFInfo
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- CA2884607A1 CA2884607A1 CA2884607A CA2884607A CA2884607A1 CA 2884607 A1 CA2884607 A1 CA 2884607A1 CA 2884607 A CA2884607 A CA 2884607A CA 2884607 A CA2884607 A CA 2884607A CA 2884607 A1 CA2884607 A1 CA 2884607A1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—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
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- A61K31/40—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
- A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
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Abstract
Disclosed herein are methods and compositions related to the treatment and/or amelioration of diseases and conditions comprising administration of acrylamido compounds, phenyl-substituted maleimide compounds, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof (e.g., Ac* and/or PSMc*). In particular, the present technology relates to administering an effective amount of acrylamido compounds and/or Ac* compounds or phenyl-substituted maleimide compounds and/or PSMc* compounds to a subject in need thereof to prevent or treat a disease or medical condition, reduce risk factors associated with a disease or medical condition, and/or reduce the severity of a medical disease or condition.
Description
THERAPEUTIC COMPOSITIONS INCLUDING ACRYLAMIDO COMPOUNDS OR
PHENYL-SUBSTITUTED MALEIMIDE COMPOUNDS AND USES THEREOF TO
PHENYL-SUBSTITUTED MALEIMIDE COMPOUNDS AND USES THEREOF TO
Claims (19)
1. A method for treating or preventing a mitochondrial disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an acrylamido compound or a phenyl-substituted maleimide compound or a pharmaceutically acceptable salt thereof, in combination with one or more additional therapeutic agents selected from the group consisting of: vitamins, cofactors, antibiotics, hormones, antineoplastic agents, steroids, immunomodulators, dermatologic drugs, antithrombotic, antianemic, and cardiovascular agents.
2. The method of claim 1, wherein the mitochondrial disease or disorder is selected from the group consisting of Alexander disease, Alpers Syndrome, Alpha-ketoglutarate dehydrogenase (AKDGH) deficiency, ALS-FTD, Sideroblastic anemia with spinocerebellar ataxia, Pyridoxine-refractory sideroblastic anemia, GRACILE
Syndrome, Björnstad Syndrome, Leigh Syndrome, mitochondrial complex III
deficiency nuclear type 1 (MC3DN1), combined oxidative phosphorylation deficiency 18 (COXPD18), Thiamine-responsive megaloblastic anemia syndrome (TRMA), Pearson Syndrome, HAM Syndrome, Ataxia, Cataract, and Diabetes Syndrome, MELAS/MERRF Overlap Syndrome, combined oxidative phosphorylation deficiency-14 (COXPD14), Infantile cerebellar-retinal degeneration (ICRD), Charlevoix-Saguenay spastic ataxia, Primary coenzyme Q10 deficiency-1 (COQ10D1), ataxia oculomotor apraxia type 1 (AOA1), Autosomal recessive spinocerebellar ataxia-9/ coenzyme Q10 deficiency-4 (COQ10D4), Ataxia, Pyramidal Syndrome, and Cytochrome Oxidase Deficiency, Friedreich's ataxia, Infantile onset spinocerebellar ataxia (IOSCA)/ Mitochondrial DNA Depletion Syndrome-7, Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL), Autosomal recessive spastic ataxia-3 (SPAX3), MIRAS, SANDO, mitochondrial spinocerebellar ataxia and epilepsy (MSCAE), spastic ataxia with optic atrophy (SPAX4), progressive external ophthalmoplegia with mitochondrial DNA
deletions autosomal dominant type 5 (PEOA5), mitochondrial complex III
deficiency nuclear type 2 (MC3DN2), episodic encephalopathy due to thiamine pyrophosphokinase deficiency/Thiamine Metabolism Dysfunction Syndrome-5 (THMD5), Spinocerebellar ataxia-28 (5CA28), autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN), Dominant Optic Atrophy (DOA), cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) Syndrome, spinocerebellar ataxia 7 (SCA7), Barth Syndrome, Biotinidase deficiency, gyrate atrophy, Syndromic Dominant Optic Atrophy and Deafness (Syndromic DOAD), Dominant Optic Atrophy plus (DOAplus), Leber's hereditary optic neuropathy (LHON), Wolfram Syndrome-1 (WFS1), Wolfram Syndrome-2 (WFS2), Age-related macular degeneration (ARMD), Brunner Syndrome, Left ventricular noncompaction-1 (LVNC1), histiocytoid cardiomyopathy, Familial Myalgia Syndrome, Parkinsonism, Fatal infantile cardioencephalomyopathy due to cytochrome c oxidase (COX) deficiency-1 (CEMCOX1), Sengers Syndrome, Cardiofaciocutaneous Syndrome-1 (CFC1), Mitochondrial trifunctional protein (MTP) deficiency, infantile encephalocardiomyopathy with cytochrome c oxidase deficiency, cardiomyopathy + encephalomyopathy, mitochondrial phosphate carrier deficiency, infantile cardioencephalomyopathy due to cytochrome c oxidase (COX) deficiency (CEMCOX2), .beta.-Hydroxyisobutyryl CoA Deacylase (HIBCH) deficiency, ECHS1) deficiency, Maternal Inheritance Leigh Syndrome (MILS), dilated cardiomyopathy with ataxia (DCMA), Mitochondrial DNA Depletion Syndrome-12 (MTDPS12), cardiomyopathy due to mitochondrial tRNA deficiencies, mitochondrial complex V (ATP synthase) deficiency nuclear type 1 (MC5DN1), combined oxidative phosphorylation deficiency-8 (COXPD8), progressive leukoencephalopathy with ovarian failure (LKENP), combined oxidative phosphorylation deficiency-10 (COXPD10), combined oxidative phosphorylation deficiency-16 (COXPD16), combined oxidative phosphorylation deficiency-17 (COXPD17), combined oxidative phosphorylation deficiency-5 (COXPD5), combined oxidative phosphorylation deficiency-9 (COXPD9), carnitine acetyltransferase (CRAT) deficiency, carnitine palmitoyltransferase I (CPT I) deficiency, myopathic carnitine deficiency, primary systemic carnitine deficiency (CDSP), carnitine palmitoyltransferase II (CPT
II) deficiency, carnitine-acylcarnitine translocase deficiency (CACTD), cartilage-hair hypoplasia, cerebrotendinous xanthomatosis (CTX), congenital adrenal hyperplasia (CAH), megaconial type congenital muscular dystrophy, cerebral creatine deficiency syndrome-3 (CCDS3), maternal nonsyndromic deafness, maternal nonsyndromic deafness, autosomal dominant deafness-64 (DFNA64), Mohr-Tranebjaerg Syndrome, Jensen Syndrome, MEGDEL, reticular dysgenesis, primary coenzyme Q10 deficiency-6 (COQ10D6), CAGSSS, diabetes, Dimethylglycine dehydrogenase deficiency (DMGDHD), Multiple Mitochondrial Dysfunctions Syndrome-1 (MMDS1), Multiple Mitochondrial Dysfunctions Syndrome-2 (MMDS2), Multiple Mitochondrial Dysfunctions Syndrome-3 (MMDS3), childhood leukoencephalopathy associated with mitochondrial Complex II deficiency, encephalopathies associated with mitochondrial Complex I deficiency, encephalopathies associated with mitochondrial Complex III deficiency, encephalopathies associated with mitochondrial Complex IV deficiency, encephalopathies associated with mitochondrial Complex V deficiency, hyperammonemia due to carbonic anhydrase VA deficiency (CA5AD), early infantile epileptic encephalopathy-3 (EIEE3), 2,4-Dienoyl-CoA reductase deficiency (DECRD), infection-induced acute encephalopathy-3 (IIAE3), ethylmalonic encephalopathy (EE), hypomyelinating leukodystrophy (HLD4), exocrine pancreatic insufficiency, dyserythropoietic anemia and calvarial hyperostosis, Glutaric aciduria type 1 (GA-1), glycine encephalopathy (GCE), hepatic failure, 2-hydroxyglutaric aciduria, 3-hydroxyacyl-CoA
dehydrogenase deficiency, familial hyperinsulinemic hypoglycemia (FHH), hypercalcemia infantile, hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) Syndrome, Immunodeficiency with hyper-IgM type 5 (HIGM5), Inclusion Body Myositis (IBM), polymyositis with mitochondrial pathology, IM-Mito, ganulomatous myopathies with anti-mitochondrial antibodies, necrotizing myopathy with pipestem capillaries, myopathy with deficient chondroitin sulfate C in skeletal muscle connective tissue, benign acute childhood myositis, idiopathic orbital myositis, masticator myopathy, hemophagocytic lymphohistiocytosis, infection-associated myositis, Facioscapulohumeral dystrophy (FSH), familial idiopathic inflammatory myopathy, Schmidt Syndrome (Diabetes mellitus, Addison disease, Myxedema), TNF receptor-associated Periodic Syndrome (TRAPS), focal myositis, autoimmune fasciitis, Spanish toxic oil-associated fasciitis, Eosinophilic fasciitis, Macrophagic myofasciitis, Graft-vs-host disease fasciitis, Eosinophilia-myalgia Syndrome, perimyositis, isovaleric acidemia (IVA), Kearnes-Sayre Syndrome (KSS), 2-oxoadipic aciduria, 2-aminoadipic aciduria, Limb-girdle Muscular Dystrophy Syndromes, leukodystrophy, Maple syrup urine disease (MSUD), 3-Methylcrotonyl-CoA carboxylase (MCC), Methylmalonic aciduria (MMA), Miller Syndrome, Mitochondrial DNA Depletion Syndrome-2 (MTDPS2), spinal muscular atrophy syndrome, rigid spine syndrome, severe myopathy with motor regression, Mitochondrial DNA Depletion Syndrome-3, MELAS Syndrome, camptocormia, MNGIE, MNGIM Syndrome, Menkes Disease, Occipital Horn Syndrome, X-linked distal spinal muscular atrophy-3 (SMAX3), methemoglobinemia, MERRF, progressive external ophthalmoplegia with myoclonus, deafness and diabetes (DD), multiple symmetric lipomatosis, Myopathy with Episodic high Creatine Kinase (MIMECK), Epilepsia Partialis Continua, malignant hyperthermia syndromes, glycogen metabolic disorders, fatty acid oxidation and lipid metabolism disorders, medication-, drug- or toxin-induced myoglobinuria, mitochondrial disorder-associated myoglobinuria, hypokalemic myopathy and rhabdomyolysis, muscle trauma-associated myoglobinuria, ischemia-induced myoglobinuria, infection-induced myoglobinuria, immune myopathies associated with myoglobinuria, Myopathy, lactic acidosis, and sideroblastic anemia (MLASA), infantile mitochondrial myopathy due to reversible COX deficiency (MMIT), Myopathy, Exercise intolerance, Encephalopathy and Lactic acidemia Syndrome, myoglobinuria and exercise intolerance syndrome, exercise intolerance, proximal weakness ~ myoglobinuria syndrome, encephalopathy and seizures syndrome, septo-optic dysplasia, exercise intolerance ~ mild weakness, myopathy ~ exercise intolerance, growth or CNS
disorder, maternally-inherited mitochondrial myopathies, myopathy with lactic acidosis, myopathy with rhabdomyolysis, Myopathy with cataract and combined respiratory chain deficiency, myopathy with abnormal mitochondrial translation, Fatigue Syndrome, myopathy with extrapyramidal movement disorders (MPXPS), glutaric aciduria II (MADD), primary COQ10 deficiency-1 (COQ10D1), primary CoQ10 deficiency-2 (COQ10D2), primary COQ10 deficiency-3 (COQ10D3), primary CoQ10 deficiency-5 (COQ10D5), secondary COQ10 deficiency, autosomal dominant mitochondrial myopathy, myopathy with focal depletion of mitochondria, mitochondrial DNA breakage syndrome (PEO + Myopathy), lipid type mitochondrial myopathy, multiple symmetric lipomatosis (MSL), N-acetylglutamate synthase (NAGS) deficiency, Nephronophthisis (NPHP), ornithine transcarbamylase (OTC) deficiency, neoplasms, NARP Syndrome, paroxysmal nonkinesigenic dyskinesia (PNKD), sporadic PEO, maternally-inherited PEO, autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions-3 (PEOA3), autosomal dominant progessive external ophthalmoplegia with mitochondrial DNA deletions-(PEOA2), autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions-1 (PEOA1), PEO+ demyelinating neuropathy, PEO +
hypogonadism, autosomal dominant progessive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOA4), distal myopathy, cachexia & PEO, autosomal dominant progressive external ophthalmoplegia-6 (PEOA6), PEO +
Myopathy and Parkinsonism, autosomal recessive progressive external ophthalmoplegia (PEOB), Mitochondrial DNA Depletion Syndrome-11 (MTDP S11), PEO with cardiomyopathy, PEPCK deficiency, Perrault Syndromes (PRLTS), propionic acidemia (PA), pyruvate carboxylase deficiency, pyruvate dehydrogenase E1-alpha deficiency (PDHAD), pyruvate dehydrogenase E1-beta deficiency (PDHBD), dihydrolipoamide dehydrogenase (DLD) deficiency, pyruvate dehydrogenase phosphatase deficiency, pyruvate dehydrogenase E3-binding protein deficiency (PDHXD), mitochondrial pyruvate carrier deficiency (MPYCD), Schwartz-Jampel Syndrome type 1 (SJS1), selenium deficiency, short-chain acyl-CoA
dehydrogenase (SCAD) deficiency, succinyl CoA:3-oxacid CoA transferase (SCOT) deficiency, Stuve-Wiedemann Syndrome (STWS), thrombocytopenia (THC), Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), Vitamin D-dependent rickets type 1 A (VDDR1A), Wilson's disease, Zellweger Syndrome (PBD3A), arsenic trioxide myopathy, myopathy and neuropathy resulting from nucleoside analogues, germanium myopathy, Parkinsonism and mitochondrial Complex I
neurotoxicity due to trichloroethylene, valproate-induced hepatic failure, neurodegeneration with brain iron accumulation-4 (NBIA4), Complex I
deficiency, Complex II deficiency, Complex III deficiency, Complex IV deficiency, Complex V
deficiency, Cytochrome c oxidase (COX) deficiency, combined complex I, II, IV, ~ V
deficiency, combined complex I, II, and III deficiency, combined oxidative phosphorylation deficiency-1 (COXPD1), combined oxidative phosphorylation deficiency-2 (COXPD2), combined oxidative phosphorylation deficiency-3 (COXPD3), combined oxidative phosphorylation deficiency-4 (COXPD4), combined oxidative phosphorylation deficiency-6 (COXPD6), combined oxidative phosphorylation deficiency-7 (COXPD7), combined oxidative phosphorylation deficiency-9 (COXPD9), combined oxidative phosphorylation deficiency-11 (COXPD11), combined oxidative phosphorylation deficiency-12 (COXPD12), combined oxidative phosphorylation deficiency-13 (COXPD13), combined oxidative phosphorylation deficiency-15 (COXPD15), combined oxidative phosphorylation deficiency-16 (COXPD16), combined oxidative phosphorylation deficiency-19 (COXPD19), combined oxidative phosphorylation deficiency-20 (COXPD20), combined oxidative phosphorylation deficiency-21 (COXPD21), fumarase deficiency, HMG-CoA synthase-2 deficiency, hyperuricemia, pulmonary hypertension, renal failure, and alkalosis (HUPRA) Syndrome, syndromic microphthalmia-7, pontocerebellar hypoplasia type 6 (PCH6), Mitochondrial DNA Depletion Syndrome-9 (MTDPS9P), and Sudden infant death Syndrome (SIDS).
Syndrome, Björnstad Syndrome, Leigh Syndrome, mitochondrial complex III
deficiency nuclear type 1 (MC3DN1), combined oxidative phosphorylation deficiency 18 (COXPD18), Thiamine-responsive megaloblastic anemia syndrome (TRMA), Pearson Syndrome, HAM Syndrome, Ataxia, Cataract, and Diabetes Syndrome, MELAS/MERRF Overlap Syndrome, combined oxidative phosphorylation deficiency-14 (COXPD14), Infantile cerebellar-retinal degeneration (ICRD), Charlevoix-Saguenay spastic ataxia, Primary coenzyme Q10 deficiency-1 (COQ10D1), ataxia oculomotor apraxia type 1 (AOA1), Autosomal recessive spinocerebellar ataxia-9/ coenzyme Q10 deficiency-4 (COQ10D4), Ataxia, Pyramidal Syndrome, and Cytochrome Oxidase Deficiency, Friedreich's ataxia, Infantile onset spinocerebellar ataxia (IOSCA)/ Mitochondrial DNA Depletion Syndrome-7, Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL), Autosomal recessive spastic ataxia-3 (SPAX3), MIRAS, SANDO, mitochondrial spinocerebellar ataxia and epilepsy (MSCAE), spastic ataxia with optic atrophy (SPAX4), progressive external ophthalmoplegia with mitochondrial DNA
deletions autosomal dominant type 5 (PEOA5), mitochondrial complex III
deficiency nuclear type 2 (MC3DN2), episodic encephalopathy due to thiamine pyrophosphokinase deficiency/Thiamine Metabolism Dysfunction Syndrome-5 (THMD5), Spinocerebellar ataxia-28 (5CA28), autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN), Dominant Optic Atrophy (DOA), cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) Syndrome, spinocerebellar ataxia 7 (SCA7), Barth Syndrome, Biotinidase deficiency, gyrate atrophy, Syndromic Dominant Optic Atrophy and Deafness (Syndromic DOAD), Dominant Optic Atrophy plus (DOAplus), Leber's hereditary optic neuropathy (LHON), Wolfram Syndrome-1 (WFS1), Wolfram Syndrome-2 (WFS2), Age-related macular degeneration (ARMD), Brunner Syndrome, Left ventricular noncompaction-1 (LVNC1), histiocytoid cardiomyopathy, Familial Myalgia Syndrome, Parkinsonism, Fatal infantile cardioencephalomyopathy due to cytochrome c oxidase (COX) deficiency-1 (CEMCOX1), Sengers Syndrome, Cardiofaciocutaneous Syndrome-1 (CFC1), Mitochondrial trifunctional protein (MTP) deficiency, infantile encephalocardiomyopathy with cytochrome c oxidase deficiency, cardiomyopathy + encephalomyopathy, mitochondrial phosphate carrier deficiency, infantile cardioencephalomyopathy due to cytochrome c oxidase (COX) deficiency (CEMCOX2), .beta.-Hydroxyisobutyryl CoA Deacylase (HIBCH) deficiency, ECHS1) deficiency, Maternal Inheritance Leigh Syndrome (MILS), dilated cardiomyopathy with ataxia (DCMA), Mitochondrial DNA Depletion Syndrome-12 (MTDPS12), cardiomyopathy due to mitochondrial tRNA deficiencies, mitochondrial complex V (ATP synthase) deficiency nuclear type 1 (MC5DN1), combined oxidative phosphorylation deficiency-8 (COXPD8), progressive leukoencephalopathy with ovarian failure (LKENP), combined oxidative phosphorylation deficiency-10 (COXPD10), combined oxidative phosphorylation deficiency-16 (COXPD16), combined oxidative phosphorylation deficiency-17 (COXPD17), combined oxidative phosphorylation deficiency-5 (COXPD5), combined oxidative phosphorylation deficiency-9 (COXPD9), carnitine acetyltransferase (CRAT) deficiency, carnitine palmitoyltransferase I (CPT I) deficiency, myopathic carnitine deficiency, primary systemic carnitine deficiency (CDSP), carnitine palmitoyltransferase II (CPT
II) deficiency, carnitine-acylcarnitine translocase deficiency (CACTD), cartilage-hair hypoplasia, cerebrotendinous xanthomatosis (CTX), congenital adrenal hyperplasia (CAH), megaconial type congenital muscular dystrophy, cerebral creatine deficiency syndrome-3 (CCDS3), maternal nonsyndromic deafness, maternal nonsyndromic deafness, autosomal dominant deafness-64 (DFNA64), Mohr-Tranebjaerg Syndrome, Jensen Syndrome, MEGDEL, reticular dysgenesis, primary coenzyme Q10 deficiency-6 (COQ10D6), CAGSSS, diabetes, Dimethylglycine dehydrogenase deficiency (DMGDHD), Multiple Mitochondrial Dysfunctions Syndrome-1 (MMDS1), Multiple Mitochondrial Dysfunctions Syndrome-2 (MMDS2), Multiple Mitochondrial Dysfunctions Syndrome-3 (MMDS3), childhood leukoencephalopathy associated with mitochondrial Complex II deficiency, encephalopathies associated with mitochondrial Complex I deficiency, encephalopathies associated with mitochondrial Complex III deficiency, encephalopathies associated with mitochondrial Complex IV deficiency, encephalopathies associated with mitochondrial Complex V deficiency, hyperammonemia due to carbonic anhydrase VA deficiency (CA5AD), early infantile epileptic encephalopathy-3 (EIEE3), 2,4-Dienoyl-CoA reductase deficiency (DECRD), infection-induced acute encephalopathy-3 (IIAE3), ethylmalonic encephalopathy (EE), hypomyelinating leukodystrophy (HLD4), exocrine pancreatic insufficiency, dyserythropoietic anemia and calvarial hyperostosis, Glutaric aciduria type 1 (GA-1), glycine encephalopathy (GCE), hepatic failure, 2-hydroxyglutaric aciduria, 3-hydroxyacyl-CoA
dehydrogenase deficiency, familial hyperinsulinemic hypoglycemia (FHH), hypercalcemia infantile, hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) Syndrome, Immunodeficiency with hyper-IgM type 5 (HIGM5), Inclusion Body Myositis (IBM), polymyositis with mitochondrial pathology, IM-Mito, ganulomatous myopathies with anti-mitochondrial antibodies, necrotizing myopathy with pipestem capillaries, myopathy with deficient chondroitin sulfate C in skeletal muscle connective tissue, benign acute childhood myositis, idiopathic orbital myositis, masticator myopathy, hemophagocytic lymphohistiocytosis, infection-associated myositis, Facioscapulohumeral dystrophy (FSH), familial idiopathic inflammatory myopathy, Schmidt Syndrome (Diabetes mellitus, Addison disease, Myxedema), TNF receptor-associated Periodic Syndrome (TRAPS), focal myositis, autoimmune fasciitis, Spanish toxic oil-associated fasciitis, Eosinophilic fasciitis, Macrophagic myofasciitis, Graft-vs-host disease fasciitis, Eosinophilia-myalgia Syndrome, perimyositis, isovaleric acidemia (IVA), Kearnes-Sayre Syndrome (KSS), 2-oxoadipic aciduria, 2-aminoadipic aciduria, Limb-girdle Muscular Dystrophy Syndromes, leukodystrophy, Maple syrup urine disease (MSUD), 3-Methylcrotonyl-CoA carboxylase (MCC), Methylmalonic aciduria (MMA), Miller Syndrome, Mitochondrial DNA Depletion Syndrome-2 (MTDPS2), spinal muscular atrophy syndrome, rigid spine syndrome, severe myopathy with motor regression, Mitochondrial DNA Depletion Syndrome-3, MELAS Syndrome, camptocormia, MNGIE, MNGIM Syndrome, Menkes Disease, Occipital Horn Syndrome, X-linked distal spinal muscular atrophy-3 (SMAX3), methemoglobinemia, MERRF, progressive external ophthalmoplegia with myoclonus, deafness and diabetes (DD), multiple symmetric lipomatosis, Myopathy with Episodic high Creatine Kinase (MIMECK), Epilepsia Partialis Continua, malignant hyperthermia syndromes, glycogen metabolic disorders, fatty acid oxidation and lipid metabolism disorders, medication-, drug- or toxin-induced myoglobinuria, mitochondrial disorder-associated myoglobinuria, hypokalemic myopathy and rhabdomyolysis, muscle trauma-associated myoglobinuria, ischemia-induced myoglobinuria, infection-induced myoglobinuria, immune myopathies associated with myoglobinuria, Myopathy, lactic acidosis, and sideroblastic anemia (MLASA), infantile mitochondrial myopathy due to reversible COX deficiency (MMIT), Myopathy, Exercise intolerance, Encephalopathy and Lactic acidemia Syndrome, myoglobinuria and exercise intolerance syndrome, exercise intolerance, proximal weakness ~ myoglobinuria syndrome, encephalopathy and seizures syndrome, septo-optic dysplasia, exercise intolerance ~ mild weakness, myopathy ~ exercise intolerance, growth or CNS
disorder, maternally-inherited mitochondrial myopathies, myopathy with lactic acidosis, myopathy with rhabdomyolysis, Myopathy with cataract and combined respiratory chain deficiency, myopathy with abnormal mitochondrial translation, Fatigue Syndrome, myopathy with extrapyramidal movement disorders (MPXPS), glutaric aciduria II (MADD), primary COQ10 deficiency-1 (COQ10D1), primary CoQ10 deficiency-2 (COQ10D2), primary COQ10 deficiency-3 (COQ10D3), primary CoQ10 deficiency-5 (COQ10D5), secondary COQ10 deficiency, autosomal dominant mitochondrial myopathy, myopathy with focal depletion of mitochondria, mitochondrial DNA breakage syndrome (PEO + Myopathy), lipid type mitochondrial myopathy, multiple symmetric lipomatosis (MSL), N-acetylglutamate synthase (NAGS) deficiency, Nephronophthisis (NPHP), ornithine transcarbamylase (OTC) deficiency, neoplasms, NARP Syndrome, paroxysmal nonkinesigenic dyskinesia (PNKD), sporadic PEO, maternally-inherited PEO, autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions-3 (PEOA3), autosomal dominant progessive external ophthalmoplegia with mitochondrial DNA deletions-(PEOA2), autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions-1 (PEOA1), PEO+ demyelinating neuropathy, PEO +
hypogonadism, autosomal dominant progessive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOA4), distal myopathy, cachexia & PEO, autosomal dominant progressive external ophthalmoplegia-6 (PEOA6), PEO +
Myopathy and Parkinsonism, autosomal recessive progressive external ophthalmoplegia (PEOB), Mitochondrial DNA Depletion Syndrome-11 (MTDP S11), PEO with cardiomyopathy, PEPCK deficiency, Perrault Syndromes (PRLTS), propionic acidemia (PA), pyruvate carboxylase deficiency, pyruvate dehydrogenase E1-alpha deficiency (PDHAD), pyruvate dehydrogenase E1-beta deficiency (PDHBD), dihydrolipoamide dehydrogenase (DLD) deficiency, pyruvate dehydrogenase phosphatase deficiency, pyruvate dehydrogenase E3-binding protein deficiency (PDHXD), mitochondrial pyruvate carrier deficiency (MPYCD), Schwartz-Jampel Syndrome type 1 (SJS1), selenium deficiency, short-chain acyl-CoA
dehydrogenase (SCAD) deficiency, succinyl CoA:3-oxacid CoA transferase (SCOT) deficiency, Stuve-Wiedemann Syndrome (STWS), thrombocytopenia (THC), Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), Vitamin D-dependent rickets type 1 A (VDDR1A), Wilson's disease, Zellweger Syndrome (PBD3A), arsenic trioxide myopathy, myopathy and neuropathy resulting from nucleoside analogues, germanium myopathy, Parkinsonism and mitochondrial Complex I
neurotoxicity due to trichloroethylene, valproate-induced hepatic failure, neurodegeneration with brain iron accumulation-4 (NBIA4), Complex I
deficiency, Complex II deficiency, Complex III deficiency, Complex IV deficiency, Complex V
deficiency, Cytochrome c oxidase (COX) deficiency, combined complex I, II, IV, ~ V
deficiency, combined complex I, II, and III deficiency, combined oxidative phosphorylation deficiency-1 (COXPD1), combined oxidative phosphorylation deficiency-2 (COXPD2), combined oxidative phosphorylation deficiency-3 (COXPD3), combined oxidative phosphorylation deficiency-4 (COXPD4), combined oxidative phosphorylation deficiency-6 (COXPD6), combined oxidative phosphorylation deficiency-7 (COXPD7), combined oxidative phosphorylation deficiency-9 (COXPD9), combined oxidative phosphorylation deficiency-11 (COXPD11), combined oxidative phosphorylation deficiency-12 (COXPD12), combined oxidative phosphorylation deficiency-13 (COXPD13), combined oxidative phosphorylation deficiency-15 (COXPD15), combined oxidative phosphorylation deficiency-16 (COXPD16), combined oxidative phosphorylation deficiency-19 (COXPD19), combined oxidative phosphorylation deficiency-20 (COXPD20), combined oxidative phosphorylation deficiency-21 (COXPD21), fumarase deficiency, HMG-CoA synthase-2 deficiency, hyperuricemia, pulmonary hypertension, renal failure, and alkalosis (HUPRA) Syndrome, syndromic microphthalmia-7, pontocerebellar hypoplasia type 6 (PCH6), Mitochondrial DNA Depletion Syndrome-9 (MTDPS9P), and Sudden infant death Syndrome (SIDS).
3. The method of any one of claims 1-2, wherein the acrylamido compound or phenyl-substituted maleimide compound, in combination with one or more additional therapeutic agents, is administered daily for one, two, three, four or five weeks.
4. The method of any one of claims 1-3, wherein the acrylamido compound or phenyl-substituted maleimide compound, in combination with one or more additional therapeutic agents, is administered daily for 6 weeks or more.
5. The method of claim 1, wherein the subject displays abnormal levels of one or more energy biomarkers compared to a normal control subject.
6. The method of claim 5, wherein the energy biomarker is selected from the group consisting of lactic acid (lactate) levels; pyruvic acid (pyruvate) levels;
lactate/pyruvate ratios; total, reduced or oxidized glutathione levels; total, reduced or oxidized cysteine levels; reduced/oxidized glutathione ratios;
reduced/oxidized cysteine ratios; phosphocreatine levels; NADH (NADH+H30) or NADPH
(NADPH+H30 ) levels; NAD or NADP levels; ATP levels; reduced coenzyme Q
(CoQred) levels; oxidized coenzyme Q (CoQox) levels; total coenzyme Q (CoQtot) levels; oxidized cytochrome C levels; reduced cytochrome C levels; oxidized cytochrome C/reduced cytochrome C ratio; acetoacetate levels; beta-hydroxy butyrate levels; acetoacetate/ beta-hydroxy butyrate ratio; 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels; levels of reactive oxygen species; oxygen consumption (VO2), carbon dioxide output (VCO2), and respiratory quotient (VCO2/VO2).
lactate/pyruvate ratios; total, reduced or oxidized glutathione levels; total, reduced or oxidized cysteine levels; reduced/oxidized glutathione ratios;
reduced/oxidized cysteine ratios; phosphocreatine levels; NADH (NADH+H30) or NADPH
(NADPH+H30 ) levels; NAD or NADP levels; ATP levels; reduced coenzyme Q
(CoQred) levels; oxidized coenzyme Q (CoQox) levels; total coenzyme Q (CoQtot) levels; oxidized cytochrome C levels; reduced cytochrome C levels; oxidized cytochrome C/reduced cytochrome C ratio; acetoacetate levels; beta-hydroxy butyrate levels; acetoacetate/ beta-hydroxy butyrate ratio; 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels; levels of reactive oxygen species; oxygen consumption (VO2), carbon dioxide output (VCO2), and respiratory quotient (VCO2/VO2).
7. The method of any one of claims 1-6, wherein the subject is human.
8. The method of any one of claims 1-7, wherein the acrylamido compound or phenyl-substituted maleimide compound is administered orally, intranasally, intrathecally, intraocularly, intradermally, transmucosally, iontophoretically, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.
9. The method of claim 1, wherein the symptoms of the mitochondrial disease or disorder comprises one or more of poor growth, loss of muscle coordination, muscle weakness, neurological deficit, seizures, autism, autistic spectrum, autistic-like features, learning disabilities, heart disease, liver disease, kidney disease, gastrointestinal disorders, severe constipation, diabetes, increased risk of infection, thyroid dysfunction, adrenal dysfunction, autonomic dysfunction, confusion, disorientation, memory loss, failure to thrive, poor coordination, sensory (vision, hearing) problems, reduced mental functions, hypotonia, disease of the organ, dementia, respiratory problems, hypoglycemia, apnea, lactic acidosis, seizures, swallowing difficulties, developmental delays, movement disorders (dystonia, muscle spasms, tremors, chorea), stroke, and brain atrophy.
10. The method of any one of claims 1-9, comprising separately, sequentially or simultaneously administering the additional therapeutic agent to the subject.
11. A method for modulating the expression of one or more energy biomarkers in a mammalian subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of an acrylamido compound or a phenyl-substituted maleimide compound or a pharmaceutically acceptable salt thereof, in combination with one or more additional therapeutic agents selected from the group consisting of: vitamins, cofactors, antibiotics, hormones, antineoplastic agents, steroids, immunomodulators, dermatologic drugs, antithrombotic, antianemic, and cardiovascular agents.
12. The method of claim 11, wherein the energy biomarker is selected from the group consisting of lactic acid (lactate) levels; pyruvic acid (pyruvate) levels;
lactate/pyruvate ratios; total, reduced or oxidized glutathione levels; total, reduced or oxidized cysteine levels; reduced/oxidized glutathione ratios;
reduced/oxidized cysteine ratios; phosphocreatine levels; NADH (NADH+H30) or NADPH
(NADPH+H30 ) levels; NAD or NADP levels; ATP levels; reduced coenzyme Q
(CoQred) levels; oxidized coenzyme Q (CoQox) levels; total coenzyme Q (CoQtot) levels; oxidized cytochrome C levels; reduced cytochrome C levels; oxidized cytochrome C/reduced cytochrome C ratio; acetoacetate levels; beta-hydroxy butyrate levels; acetoacetate/ beta-hydroxy butyrate ratio; 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels; levels of reactive oxygen species; oxygen consumption (VO2), carbon dioxide output (VCO2), and respiratory quotient (VCO2/VO2).
lactate/pyruvate ratios; total, reduced or oxidized glutathione levels; total, reduced or oxidized cysteine levels; reduced/oxidized glutathione ratios;
reduced/oxidized cysteine ratios; phosphocreatine levels; NADH (NADH+H30) or NADPH
(NADPH+H30 ) levels; NAD or NADP levels; ATP levels; reduced coenzyme Q
(CoQred) levels; oxidized coenzyme Q (CoQox) levels; total coenzyme Q (CoQtot) levels; oxidized cytochrome C levels; reduced cytochrome C levels; oxidized cytochrome C/reduced cytochrome C ratio; acetoacetate levels; beta-hydroxy butyrate levels; acetoacetate/ beta-hydroxy butyrate ratio; 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels; levels of reactive oxygen species; oxygen consumption (VO2), carbon dioxide output (VCO2), and respiratory quotient (VCO2/VO2).
13. The method of any one of claims 11-12, wherein the acrylamido compound or phenyl-substituted maleimide compound, in combination with one or more additional therapeutic agents, is administered daily for one, two, three, four or five weeks.
14. The method of any one of claims 11-13, wherein the acrylamido compound or phenyl-substituted maleimide compound, in combination with one or more additional therapeutic agents, is administered daily for 6 weeks or more.
15. The method of any one of claims 11-14, wherein the subject has been diagnosed has having, is suspected of having, or is at risk of having a mitochondrial disease or disorder.
16. The method of claim 15, wherein symptoms of the mitochondrial disease or disorder comprises one or more of poor growth, loss of muscle coordination, muscle weakness, neurological deficit, seizures, autism, autistic spectrum, autistic-like features, learning disabilities, heart disease, liver disease, kidney disease, gastrointestinal disorders, severe constipation, diabetes, increased risk of infection, thyroid dysfunction, adrenal dysfunction, autonomic dysfunction, confusion, disorientation, memory loss, failure to thrive, poor coordination, sensory (vision, hearing) problems, reduced mental functions, hypotonia, disease of the organ, dementia, respiratory problems, hypoglycemia, apnea, lactic acidosis, seizures, swallowing difficulties, developmental delays, movement disorders (dystonia, muscle spasms, tremors, chorea), stroke, and brain atrophy. .
17. The method of any one of claims 11-16, wherein the subject is human.
18. The method of any one of claims 11-17, wherein the acrylamido compound or phenyl-substituted maleimide compound is administered orally, intranasally, intrathecally, intraocularly, intradermally, transmucosally, iontophoretically, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.
19. The method of any one of claims 11-18, wherein the additional therapeutic agent is administered separately, sequentially or simultaneously to the subject.
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| CA2884607A CA2884607A1 (en) | 2015-03-11 | 2015-03-11 | Therapeutic compositions including acrylamido compounds or phenyl-substiituted maleimide compounds and uses thereof to treat and prevent mitochondrial diseases and conditions |
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| CA2884607A CA2884607A1 (en) | 2015-03-11 | 2015-03-11 | Therapeutic compositions including acrylamido compounds or phenyl-substiituted maleimide compounds and uses thereof to treat and prevent mitochondrial diseases and conditions |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018170109A1 (en) * | 2017-03-15 | 2018-09-20 | Lunella Biotech, Inc. | Mitoriboscins: mitochondrial-based therapeutics targeting cancer cells, bacteria, and pathogenic yeast |
| WO2022049377A1 (en) | 2020-09-01 | 2022-03-10 | Nrg Therapeutics Ltd | Novel compounds |
| WO2022049376A1 (en) | 2020-09-01 | 2022-03-10 | Nrg Therapeutics Ltd | Novel compounds |
| WO2023166303A1 (en) | 2022-03-02 | 2023-09-07 | Nrg Therapeutics Ltd | Acrylamide compounds |
-
2015
- 2015-03-11 CA CA2884607A patent/CA2884607A1/en not_active Abandoned
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018170109A1 (en) * | 2017-03-15 | 2018-09-20 | Lunella Biotech, Inc. | Mitoriboscins: mitochondrial-based therapeutics targeting cancer cells, bacteria, and pathogenic yeast |
| US10512618B2 (en) | 2017-03-15 | 2019-12-24 | Lunella Biotech, Inc. | Mitoriboscins: mitochondrial-based therapeutics targeting cancer cells, bacteria, and pathogenic yeast |
| CN110621655A (en) * | 2017-03-15 | 2019-12-27 | 卢内拉生物技术有限公司 | Mitoripiscin: mitochondria-based therapeutics targeting cancer cells, bacteria and pathogenic yeast |
| JP2020514418A (en) * | 2017-03-15 | 2020-05-21 | ルネラ・バイオテック・インコーポレーテッド | Mitribosin: a mitochondrial-based therapeutic targeting cancer cells, bacteria, and pathogenic yeast |
| US11311501B2 (en) | 2017-03-15 | 2022-04-26 | Lunella Biotech, Inc. | Mitoriboscins: mitochondrial-based therapeutics targeting cancer cells, bacteria, and pathogenic yeast |
| US11364210B2 (en) | 2017-03-15 | 2022-06-21 | Lunella Biotech, Inc. | Mitoriboscins: mitochondrial-based therapeutics targeting cancer cells, bacteria and pathogenic yeast |
| US11547679B2 (en) | 2017-03-15 | 2023-01-10 | Lunella Biotech, Inc. | Mitoriboscins: mitochondrial-based therapeutics targeting cancer cells, bacteria and pathogenic yeast |
| CN110621655B (en) * | 2017-03-15 | 2023-03-10 | 卢内拉生物技术有限公司 | Mitoripiscin: mitochondrially based therapeutics targeting cancer cells, bacteria and pathogenic yeast |
| WO2022049377A1 (en) | 2020-09-01 | 2022-03-10 | Nrg Therapeutics Ltd | Novel compounds |
| WO2022049376A1 (en) | 2020-09-01 | 2022-03-10 | Nrg Therapeutics Ltd | Novel compounds |
| WO2023166303A1 (en) | 2022-03-02 | 2023-09-07 | Nrg Therapeutics Ltd | Acrylamide compounds |
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