Novel components of the human metabolome: the identification, characterization and anti-inflammatory activity of two 5-androstene tetrols.
Two natural 5-androstene steroid tetrols, androst-5-ene-3β,7β,16α,17β-tetrol (HE3177) and androst-5-ene-3α,7β,16α,17β-tetrol (HE3413), were discovered in human plasma and urine. These compounds had significant aqueous solubility, did not bind or transactivate steroid-binding nuclear hormone receptors, and were not immunosuppressive in murine mixed-lymphocyte studies. Both compounds appear to be metabolic end products, as they were resistant to primary and secondary metabolism. Both were orally bioavailable, and were very well tolerated in a two-week dose-intensive toxicity study in mice. Anti-inflammatory properties were found with exogenous administration of these compounds in rodent disease models of multiple sclerosis, lung injury, chronic prostatitis, and colitis.
Harbor Biosciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USA. cahlem@harborbiosciences.com
Clarence N
CN
Ahlem
Theodore M
TM
Page
Dominick L
DL
Auci
Michael R
MR
Kennedy
Katia
K
Mangano
Ferdinando
F
Nicoletti
Yu
Y
Ge
Yujin
Y
Huang
Steven K
SK
White
Sonia
S
Villegas
Douglas
D
Conrad
Angela
A
Wang
Christopher L
CL
Reading
James M
JM
Frincke
D000293:Adolescent; D000328:Adult; D000368:Aged; D000737:Androstenols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D008968:Molecular Conformation; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D011472:Prostatitis / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D012995:Solubility; D013237:Stereoisomerism; D055815:Young Adult
D000737:Androstenols; D000893:Anti-Inflammatory Agents; C557015:androst-5-ene-3,7,16,17-tetrol