Bimosiamose

Bimosiamose is a metabolite of the biotin-dependent enzyme, methionine adenosyltransferase. It is an activated form of SAMe and has been shown to have beneficial effects in treating patients with metabolic disorders. Bimosiamose also has anti-inflammatory properties and can be used as an adjunct therapy for bowel disease. In vitro studies have shown that bimosiamose inhibits the activity of monoclonal antibodies that bind to the CD20 receptor on hl-60 cells, which causes these cells to die by apoptosis. This compound is also able to inhibit the production of inflammatory cytokines, such as IL-6 and TNF-α, in vitro.

Bimosiamose is a pan-selectin inhibitor (IC50s = 88, 20, and 86 µM for E-, P-, and L-selectin, respectively). It reduces adhesion of HL-60 cells to E- and P-selectin when used at a concentration of 129 µM. In vivo, bimosiamose (200 mg/kg) reduces skin scaliness, induration, and erythema in a patient-derived xenograft mouse model of psoriasis. It decreases hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and myeloperoxidase (MPO) levels and reduces neutrophil infiltration in a rat model of severe hepatic ischemia-reperfusion injury. Bimosiamose also prevents nematode-induced late airway reactivity in sheep and reduces airway hyperresponsiveness in a mouse model of asthma.

Bimosiamose, also known as TBC-1269, is a L/E/P-selectin antagonist potentially for the treatment of asthma, chronic obstructive pulmonary. Bimosiamose attenuates airway inflammation in COPD. Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics.

Title: Bimosiamose

CAS Registry Number: 187269-40-5

CAS Name: 3',3'''-(1,6-Hexanediyl)bis[6'-(a-D-mannopyranosyloxy)[1,1'-biphenyl]]-3-acetic acid

Additional Names: 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-a-D-mannopyranosyloxy)phenyl]hexane

Manufacturers' Codes: TBC-1269

Molecular Formula: C46H54O16

Molecular Weight: 862.91

Percent Composition: C 64.03%, H 6.31%, O 29.67%

Literature References: Pan-selectin receptor antagonist. Prepn: T. P. Kogan et al., WO 9701335; eidem, US 5919768 (1997, 1999 both to Texas Biotechnol.); eidem, J. Med. Chem. 41, 1099 (1998). Stereospecific synthesis: I. L. Scott et al., Carbohydr. Res. 317, 210 (1999). Review of pharmacology and clinical development: L. Pradella, Curr. Opin. Anti-Inflam. Immunomod. Invest. Drugs 1, 56-60 (1999); E. Aydt, G. Wolff, Pathobiology 70, 297-301 (2003). Clinical pharmacokinetics: M. Meyer et al., Int. J. Clin. Pharmacol. Ther. 43, 463 (2005). Clinical evaluation in allergic asthma: K. M. Beeh et al., Pulm. Pharmacol. Ther. 19, 233 (2006).

Properties: White solid, mp 115-117°.

Melting point: mp 115-117°

Derivative Type: Disodium salt

CAS Registry Number: 187269-60-9

Manufacturers' Codes: TBC-1269z

Molecular Formula: C46H52Na2O16

Molecular Weight: 906.88

Percent Composition: C 60.92%, H 5.78%, Na 5.07%, O 28.23%

Properties: Slightly hygroscopic white powder, mp 243-245°.

Melting point: mp 243-245°

Therap-Cat: Anti-inflammatory

Keywords: Anti-inflammatory (Biological Response Modifier).