Oral treatment with HE3286 ameliorates disease in rodent models of rheumatoid arthritis.
HE3286 (17alpha-ethynyl-5-androstene-3beta, 7beta, 17beta-triol) is an orally bio-available synthetic derivative of naturally occurring androstene-3beta, 7beta, 17beta-triol. Our present data show that oral treatment with HE3286, favourably influenced the course of arthritis in the rat model of adjuvant-induced arthritis (reduced cumulative disease scores and paw edema), and in the mouse model of collagen antibody-induced arthritis (reduced clinical paw scores). Importantly, HE3286 was not immune suppressive in human mixed lymphocyte reaction or in animals challenged with Coxsackie B3 virus. HE3286 is currently in phase I/II clinical trials in rheumatoid arthritis and ulcerative colitis and these findings further strengthen the possibility that HE3286 may represent an effective anti-inflammatory agent useful for treating chronic inflammation with a more attractive safety profile than glucocorticoids or cyclooxygenase inhibitors.
Auci
Dominick L
DL
HollisEden Pharmaceuticals, San Diego, CA, USA.
Mangano
Katia
K
Destiche
Daniel
D
White
Steven K
SK
Huang
Yujin
Y
Boyle
David
D
Frincke
James
J
Reading
Christopher L
CL
Nicoletti
Ferdinando
F
D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D001835:Body Weight; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D029822:Enterovirus B, Human / Q000502:physiology; D006801:Humans; D007114:Immunization; D015850:Interleukin-6 / Q000097:blood; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000188:drug therapy / Q000821:virology; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
C524733:17-ethynyl-5-androstene-3, 7, 17-triol; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003687:Dehydroepiandrosterone; D009195:Peroxidase