Cell lines

MDA-MB-231 breast adenocarcinoma cell

Preparation method

Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μmol/l

Applications

In blood containing MDA-MB-231 cells, a combination of SB273005 and lamifiban inhibited tumor cell adhesion to vascular extracellular matrix (ECM).

Animal models

Male Lewis rats with adjuvant-induced arthritis

Dosage form

Oral administration, 10, 30, and 60 mg/kg, twice per day

Application

In rat with adjuvant-induced arthritis, SB273005 (30 mg/kg, 60 mg/kg, p.o.) significantly reduced the symptoms of adjuvant-induced arthritis. When administered prophylactically to AIA rats, SB 273005 (twice per day) inhibited paw edema at doses of 10, 30, and 60 mg/kg, by 40%, 50%, and 52%, respectively.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

• Mol Ther : S1525-0016.PMID:35619555

SB 273005 is a potent nonpeptide antagonist of αvβ3 (vitronectin receptor), with Ki values of 1.2 nM and 0.3 nM to two closely related integrins, αvβ3 and αvβ5, respectively [1].

αvβ3 belongs to the integrin family of adhesion molecules. It is a heterodimer. It mediates cell adhesion to serum proteins and extracellular matrix via the recognition of the arg-gly-asp (RGD) sequence [1].

SB 273005 binds αvβ3 and αvβ5 with low nM affinity, but binds weakly to integrins αIIbβ3 and α5β1. SB 273005 inhibits αvβ3-mediated cell adhesion with an IC50 value of 3 nM, endothelial cell migration with an IC50 of 1.8 nM, and osteoclast-mediated bone resorption with an IC50 of 11 nM in vitro [1].

The αvβ3 integrin is pivotal in bone resorption [2]. In the chronic ovx and thyroparathyroidectomized bone resorption rat models, SB 273005 as well as other similar vitronectin receptor antagonists, inhibit bone loss. In AIA rats, prophylactical treatment with SB 273005 at doses of 60, 30, and 10 mg/kg twice daily significantly normalized bone mineral density (BMD). Normalization values of BMD were 69%, 42%, and 44% for doses of 60, 30, and 10 mg/kg twice daily, respectively. A single daily dose of SB 273005 significantly improved BMD (24% normalization) only when SB 273005 was prophylactically administered at 60 mg/kg [1].

References:
[1]. Badger AM, Blake S, Kapadia R, et al. Disease-modifying activity of SB 273005, an orally active, nonpeptide αvβ3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthritis. Arthritis & Rheumatism, 2001, 44(1): 128-137.
[2]. Murphy MG, Cerchio K, Stoch SA, et al. Effect of L-000845704, an αvβ3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. The Journal of Clinical Endocrinology & Metabolism, 2005, 90(4): 2022-2028.