SB 699551 is a selective 5-HT5A antagonist (Ki=6.31 nM) that enhances 5-HT neuronal function. It inhibits SERT (Ki=25.12 nM), reduces phosphorylation levels of AKT and FOXO1, and exhibits inhibitory effects against breast cancer.

5-HT5A Receptor:8.3 (pKi)

In the tumor spheroid formation assay using the Homo sapiens breast cancer cell lines MCF-7 and HCC1954, SB 699551 (treatment duration: 72 hours) inhibited the frequency of tumor sphere-initiating cells, with half-maximal inhibitory concentrations (IC₅₀) of 0.2 μM and 0.3 μM, respectively [1].
SB 699551 (treatment duration: 5–60 minutes) increased the phosphorylation levels of CREB and ATF1 while decreasing the phosphorylation levels of AKT, PRAS40, P70S6K, FOXO1, and S6RP in breast cancer cell lines (MCF-7 and MDA-MB-157) [2].
SB 699551 (concentration: 10 μM) was involved in regulating the motor output of frog spinal motor neurons and affected the amplitude of antidromic field potentials [3].

In the NOD/SCID mouse breast cancer parasite Spilurus subsp. spilurus xenograft model, SB 699551 (25 mg/kg, intraperitoneal injection, once daily for 3 weeks) not only significantly inhibited the growth rate of the transplanted tumors but also exhibited synergistic effects with Docetaxel, further promoting tumor volume reduction [1].
In Sprague-Dawley rats, a single intraperitoneal injection of SB 699551 (0.3-3 mg/kg) reversed drug-induced cognitive dysfunction, specifically manifested as improved performance in attentional set-shifting tasks and novel object recognition tasks, along with alleviation of social withdrawal behavior [4].
When administered as a single subcutaneous injection (0.3-3 mg/kg) in combination with Dizocilpine or Scopolamine, SB 699551 reversed long-term memory impairment (amnesia) in Wistar rats [5].