SM-276001

SM-276001 is a potent selective TLR7 agonist that can induce antitumor immune responses. SM-276001 is an orally active interferon (IFN) inducer[1][2].

Signaling Pathways >> Immunology/Inflammation >> Toll-like Receptor (TLR)

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> IFNAR

Research Areas >> Inflammation/Immunology

TLR7; IFN[1][2]

SM-276001 (1 nM-10 μM) dose-dependently activates NF-κB through human TLR7[2].

SM-276001 demonstrates potent IFN-inducing activity at a dose of 0.1 mg/kg by oral administration in mice[1]. Oral administration of SM-276001, leads to the induction of an inflammatory cytokine and chemokine milieu and to the activation of a diverse population of immune effector cells including T and B lymphocytes, NK and NKT cells[2]. SM-276001 (3 mg/kg PO biweekly) significantly inhibits tumor growth in the Renca renal cell cancer and CT26 colorectal models[2]. SM-276001 (orally; 0.1, 1 or 10 mg/kg) leads to the activation of a diverse population of spleen-resident immune effector cells in Balb/c and C57BL/6J mice. When administered at 1 mg/kg or greater, the plasma concentration of SM-276001 exceeds the MEC of 30 nM[2]. Animal Model: C57BL/6 and B6C3F1 mice bearing Renca or CT26 tumors[2] Dosage: 3 mg/kg Administration: Oral administration twice weekly for 25 days Result: Significantly reduced disease burden in mice bearing either Renca or CT26 tumors.

[1]. Isobe Y, et al. Synthesis and biological evaluation of novel 9-substituted-8-hydroxyadenine derivatives as potent interferon inducers. J Med Chem. 2006 Mar 23;49(6):2088-95.

[2]. Koga-Yamakawa E, et al. Intratracheal and oral administration of SM-276001: a selective TLR7 agonist, leads to antitumor efficacy in primary and metastatic models of cancer. Int J Cancer. 2013 Feb 1;132(3):580-90.