SB-699551

SB-699551 is a selective and brain penetrant 5-HT5A receptor antagonist with a pK_i of 8.2 nM. SB-699551 shows high selectivity over most other 5-HT receptor subtypes, dopamine receptors, and α1B adrenoceptor. SB-699551 disrupts Gαi/o-coupled and PI3K/AKT/mTOR signaling pathways, alters CREB, ATF1, AKT, PRAS40, S6K, and FOXO1 phosphorylation in breast tumor cells. SB-699551 can be used for the research of anxiety, breast cancer, and Alzheimer's disease^{[1][2][3][4][5]}. IC50 & Target:5-HT5A^[1] In Vitro:SB-699551 potently binds to human 5-HT_5A receptors expressed in CHO cells with a pK_i of 8.2 and exhibits ≥100-fold selectivity against most other 5-HT receptor subtypes^[1].
SB-699551 (1 μM) acts as a competitive antagonist at human 5-HT_5A receptors expressed in HEK 293 cells, with an apparent pK_B of 8.0^[1].
SB-699551 (72 h) inhibits tumorsphere formation and cell viability in HCC1954 and MCF-7 human breast tumor cell lines with IC₅₀ values ranging from 0.2 to 0.3 μM^[3].
SB-699551 inhibits tumorsphere formation in PDX-derived human breast tumor cell lines (PDX 81, PDX 18, PDX 12) with IC₅₀ values ranging from 470 nM to 775 nM, independent of subtype^[3].
SB-699551 (4 μM, 30 min; 4 μM, 5-60 min; 3-5 μM, 24 h) modulates signaling via the Gα_i/o pathway and the PI3K/AKT/mTOR axis in MCF-7 and MDA-MB-157 human breast tumor cell lines, with increased CREB phosphorylation and reduced phosphorylation of AKT and downstream targets^[3]. In Vivo:SB-699551 (3-30 mg/kg; i.p.; once) exhibits dose-dependent sedative effects on motor behavior in healthy rats in the open field and forced swim tests (FST)^[2].
SB-699551 (3-60 mg/kg; i.p.; once) shows anxiolytic-like effects in the foot-shock-induced USV model with an ED₅₀ of 25.4 mg/kg^[2].
SB-699551-A (3-30 mg/kg; i.p.; three times: 23.5, 5, and 1 h before test) does not exhibit antidepressant-like effects in the forced swim test^[2].
SB-699551 (25 mg/kg; i.p.; 5 days a week; 3 weeks) reduces human breast tumor xenograft growth in NOD/SCID mice^[3].
SB-699551 (0.1-3.0 mg/kg; s.c.; single injection post-first autoshaping session) impairs short-term memory at 0.3 mg/kg and long-term memory at 0.3, 1.0, and 3.0 mg/kg in male Wistar rats in an autoshaping associative learning task^[4].
SB-699551 (0.3-3.0 mg/kg; s.c.) prevents forgetting induced by a 216-hour interruption of autoshaping training in rats^[5].
SB-699551 (0.3 mg/kg; s.c.) alone induces amnesia-like effects in rats, with co-administration with Dizocilpine (HY-15084B) reversing these effects in 48-hour long-term memory and co-administration with Scopolamine (HY-N0296) reversing effects in 1.5-hour short-term and 24- and 48-hour long-term memory^[5].