HMGB1 antagonist treatment of severe sepsis

1. A method of treating a mammal for a disease or condition comprising administering to the mammal a therapeutically effective amount of a peptidomimetic molecule of the formula:

wherein:

R 1 is CH or N; and

R 2 is CH or N,

provided that at least one of R 1 or R 2 is N,

wherein the disease or condition is selected from the group consisting of non-influenza pulmonary infections, smoke or toxic gas inhalation, gastric acid aspiration, transfusion reactions, reactions and injuries caused by mechanical ventilation, hemorrhagic shock, endotoxemia; autoimmune diseases selected from the group consisting of dermatomyositis, multiple sclerosis, systemic lupus erythematosus (SLE), celiac disease, chronic fatigue syndrome, Crohn's disease, type 1 diabetes, Graves disease, chronic Lyme disease, myocarditis, myositis, polymyositis, post-myocardial infarction syndrome, psoriasis, rheumatic fever, scleroderma, Sjogren's syndrome, thrombocytopenia, and ulcerative colitis; neurodegenerative diseases selected from the group consisting of Alzheimer's, mild cognitive impairment (pre-Alzheimer's), Parkinson's disease, and amyotrophic lateral sclerosis (ALS); arthritis selected from the group consisting of osteoarthritis (OA), arthritic joint inflammation, juvenile idiopathic arthritis (JIA), serum rheumatoid arthritis (RA), juvenile arthritis, psoriatic arthritis, and reactive arthritis; asthma; cancer selected from the group consisting of pancreatic cancer, colorectal cancer and skin cancers; cardiac and vessel disease selected from the group consisting of coronary artery disease (CAD), coronary heart disease, acute coronary, atherosclerosis, and heart failure; type 2 diabetes; β-cell transplantation in diabetes; lung injury and lung related diseases selected from the group consisting of chronic obstruction pulmonary disease (COPD), pulmonary hypertension, pulmonary fibrosis, acute lung injury, cystic fibrosis, inflammatory lung disease, and pneumonia; Intensive care unit patients being treated for systemic inflammatory response syndrome, severe trauma, blunt chest trauma, hemorrhagic shock/trauma, traumatic brain injury, stroke, spinal cord injury, influenza, chemical toxicity, severe viral or bacterial infections; post-sepsis impairments selected from the group consisting of cognitive impairments, persistent splenomegaly, post sepsis anemia; post-surgery neurocognitive disorders; acetaminophen-induced liver injury; ethanol-induced liver diseases; cryopyrin-associated autoinflammatory syndrome, bleomycin induced lung fibrosis; paracetamol intoxication; nociceptive pain; cardiac ischemia; cerebral ischemia; skeletal muscle ischemia; inflammatory bowel disease; kidney and liver related disease selected from the group consisting of kidney failure, liver failure, hepatic ischemia/reperfusion injury, acute kidney injury (CHD), chronic kidney disease (CKD), acute liver failure (ALF), liver fibrosis, and alcoholic liver disease; trauma/ischemia caused by transplant and graft-versus-host disease; obesity/metabolic syndrome; pancreatitis; preeclampsia; epilepsy; pulmonary arterial hypertension (PAH); chronic pain; chronic inflammation; GI bleeding; colitis; anemia; hemophilia; traumatic brain injury; concussion; and migraines.

2. The method of claim 1 , wherein the therapeutically effective amount is orally administered to the mammal.

3. The method of claim 1 , wherein the therapeutically effective amount is intravenously administered to the mammal.

4. The method of claim 1 , wherein the mammal is human.

5. The method of claim 1 , wherein R 1 is CH and R 2 is N.

6. The method according to claim 1 , wherein R 1 is N and R 2 is CH.

7. The method of claim 1 , wherein the peptidomimetic molecule is of the formula:

8. The method of claim 1 , wherein the method of administration is selected from the group consisting of oral delivery, parenteral delivery, buccal delivery, sublingual delivery, nasal delivery, inhalation delivery, nebulization delivery, topical delivery, transdermal delivery and suppository delivery.

9. The method of claim 7 , wherein the peptidomimetic molecule is combined with an excipient comprising PBS:PEG 300:propylene glycol:polysorbate 80 at 50:40:5:5.

10. A method of treating a mammal for a disease or condition comprising administering to the mammal a therapeutically effective amount of a peptidomimetic molecule of the formula:

wherein:

R 1 is CH or N; and

R 2 is CH or N,

provided that at least one of R 1 or R 2 is N,

wherein the disease or condition is selected from the group consisting of pain, fever, inflammation, and a combination thereof caused by rheumatic fever, viral infections, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, myositis, neuralgia, synovitis, gout, ankylosing spondylitis, bursitis, burns, peptic ulcers, gastritis, regional enteritis, ulcerative colitis, and diverticulitis.