SB 452533

SB 452533 is a potent and selective TRPV1 antagonist with the pKb of 7.8[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Inflammation/Immunology

SB 452533 is potent as an antagonist at the cloned recombinant rat TRPV1 receptor in HEK293 cells with a pKb of 7.7 and a pIC50 of 7.0[1]. SB-452533 reduces phosphorylation of CAMKK2 and AMPK[2]. Western Blot Analysis[2] Cell Line: Skeletal muscle (C2C12) cells Concentration: 0, 50, 100, 200, and 400 μM Incubation Time: 30 minutes; followed by 200 μM Capsaicin treatment for another 30 min. Result: Significantly reduced Capsaicin-induced phosphorylation of AMPK and CAMKK2.

Capsaicin (Cap; small dose 2 mg/kg) significantly reduces Bleomycin-induced pulmonary fibrosis in mice. SB-452533 abolishes the effects of small dose Cap[3]. Animal Model: BALB/c mice bearing pulmonary fibrosis model[3] Dosage: 2.5 mg/kg Administration: Treatment received daily drug via subcutaneous injection for 21 days Result: The effect (reduced Bleomycin-induced pulmonary fibrosis) of Cap were abolished in the presence of SB-452533.

[1]. Harshad K Rami, et al. Discovery of small molecule antagonists of TRPV1. Bioorg Med Chem Lett. 2004 Jul 16;14(14):3631-4.

[2]. Parisa Vahidi Ferdowsi, et al. TRPV1 Activation by Capsaicin Mediates Glucose Oxidation and ATP Production Independent of Insulin Signalling in Mouse Skeletal Muscle Cells. Cells. 2021 Jun 21;10(6):1560.

[3]. Lin Ming Lu, et al. Effect of small dose capsaicin for treatment of pulmonary fibrosis in mice and its mechanism. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2020 May;36(3):216-222.