Utility of nematode small molecules
The present invention relates to methods of treating immune disorders and/or inflammation using certain modulator compounds. In one embodiment, the present invention provides a method of treating an immune and inflammatory disorders disorder by administering a composition comprising a therapeutically effective dosage of an ascaroside compound, or a mixture of ascaroside compounds, or a mixture containing at least one ascaroside.
1. A method of reducing eosinophils (eos) or lymphocytes (lym), or both, in a subject, comprising:
administering a therapeutically effective dosage of a composition to the subject, thereby reducing eos or lym, or both, in the subject,
wherein the composition comprises a pharmaceutically acceptable carrier and a compound of Formula (I)
wherein
R 1 is, independently for each occurrence, hydrogen or alkyl;
R 1′ is, independently for each occurrence, hydrogen or alkyl;
X is C(R 1 ) 2 ;
X 1 is cis- or trans-C(R 1 )═C(R 1 );
n1, n2, and n3 are each independently an integer of 0 to 30, inclusive;
n4 is an integer of 1 to 30, inclusive;
the sum of n1, each n2, and each n3 is 1 to 30, inclusive;
R 3 is hydrogen or alkyl;
R 4 is hydrogen or alkyl;
R 5′ is hydrogen, alkyl, halogen, —OR 6 , or —N(R 6 ) 2 ;
R 5 is —OR 6 or —N(R 6 ) 2 ; and
R 6 is independently alkyl, alkenyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, aryl, or heteroaryl is optionally substituted,
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein R 3 is hydrogen.
3. The method of claim 1 , wherein R 4 is hydrogen.
4. The method of claim 1 , wherein R 5′ is alkyl.
5. The method of claim 1 , wherein R 5 is OR 6 .
6. The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (Ia):
wherein
R 1a is hydrogen or methyl;
n is an integer from 0 to 6, inclusive;
represents a single bond or a double bond; and
R 5a is —OR 6 ,
or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein R 1a is methyl.
8. The method of claim 6 , wherein n is an integer from 0 to 4, inclusive.
9. The method of claim 1 , thereby reducing mucus production in the subject.
10. The method of claim 1 , wherein the subject is a human.
11. The method of claim 1 , wherein the subject is selected from primates, humans, equines, horses, cattle, cows, swine, sheep, rodents, rats, pets, dogs, and guinea pigs.
12. The method of claim 1 , wherein the method is a method of treating acne vulgaris, asthma, an autoimmune disease, celiac disease, chronic prostatitis, glomerulonephritis, hypersensitivity, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, interstitial cystitis, lupus, scleroderma, hemolytic anemia, type one diabetes, Graves' disease, multiple sclerosis, Goodpasture's syndrome, pernicious anemia, myopathy, seasonal allergy, mastocytosis, perennial allergy, anaphylaxis, food allergy, allergic rhinitis, atopic dermatitis, or autism.
13. The method of claim 1 , wherein the method is a method of reducing eos in the subject.
14. The method of claim 1 , wherein the method is a method of reducing lym in the subject.
15. The method of claim 1 , wherein the method is a method of reducing eos and lym in the subject.
16. The method of claim 1 , wherein the method is a method of treating an inflammatory disorder, an autoimmune disorder, or both.
17. The method of claim 1 , wherein method is a method of treating asthma, inflammatory bowel disease, rheumatoid arthritis, or multiple sclerosis.