Cat Number: API913611979

Brexpiprazole

Standard	Qualification
Facility GMP	DMF

NaviID

Antipsychotic APIs

CAS Number

913611-97-9

EINECS

811-628-7

Synonyms

Rexulti; OPC-34712; 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one

Molecular Formula

C25H27N3O2S

Molecular Weight

433.6

Smiles

C1CN(CCN1CCCCOC2=CC3=C(C=C2)C=CC(=O)N3)C4=C5C=CSC5=CC=C4

InChIKey

ZKIAIYBUSXZPLP-UHFFFAOYSA-N

Appearance

White solid

pKa

11.22±0.70

Melting Point

135.1℃

Boiling Point

675.2 ℃

Relative Density

1.245

General Description

Brexpiprazole is an advanced-generation Atypical Antipsychotic, and Serotonin–Dopamine Activity Modulator (SDAM). Brexpiprazole shows better tolerance than other drugs in its class, with less unwanted side effects such as akathisia.

Mechanism of Action

Brexpiprazole's mechanism of action centers around its multitarget receptor activity. It functions as a partial agonist at the Dopamine D2 and Serotonin 5-HT1A receptors, while also acting as an antagonist at the Serotonin 5-HT2A receptor. This unique receptor affinity profile is believed to contribute to the balancing of dopaminergic and serotonergic activity in the brain, resulting in its antipsychotic action, antidepressant augmentation, and more favorable tolerability characteristics.

Application

Brexpiprazole is currently used as a treatment for schizophrenia in adults. It is also considered effective at augmenting the response to traditional antidepressants in adults with Major Depressive Disorder (MDD), with a slightly faster onset of action. Additionally, there is some emerging research into the possible anticancer effects of Brexpiprazole.

Scientific Support Content

Brexpiprazole is a serotonin–dopamine activity modulator (SDAM) which is a partial agonist for the D2/D3 receptors and the 5-HT1A receptor and an antagonist for the 5-HT2A receptor. It has the same antipsychotic properties as aripiprazole, but with a different side effect profile. As a therapy for oncology, Brexpiprazole's mechanism of action is primarily through down-regulation of the anti-apoptotic protein survivin, which is important for maintaining CSC viability and resistance to EGFR TKIs. By decreasing survivin transcription, brexpiprazole lowers mitochondrial stability, leading to activation of caspase-dependent apoptosis, and sensitizes GSCs to osimertinib (a third-generation EGFR-TKI). The drug shows similar efficacy in both wild type EGFR and EGFRvIII positive cells, and this effect is independent of canonical EGFR downstream pathways. Pharmacologic inhibition or genetic knock-down of survivin recapitulates the chemosensitizing activity of brexpiprazole, thus confirming survivin as the relevant target.
In addition to Glioblastoma, this has also been shown to increase the efficacy of gemcitabine and 5-fluorouracil in pancreatic and non-small-cell lung cancer stem cells, making it a potentially broad-spectrum CSC-targeting adjuvant.

Scientific Support Picture

Brexpiprazole2.png

Scientific Support alt

Fig. 1 Brexpiprazole sensitizes glioma stem cells to Osimertinib. (Suzuki S.; et al. 2019)

Scientific Support Reference

Suzuki S, et al. Brexpiprazole, a serotonin-dopamine activity modulator, can sensitize glioma stem cells to osimertinib, a third-generation EGFR-TKI, via survivin reduction. Cancers, 2019, 11(7): 947.

Advanced Innovations

Brexpiprazole - Protheragen

FAQs

[{
"question": "Can you supply Brexpiprazole with custom specifications?",
"answer": "Yes, we provide customized specifications and packaging for Brexpiprazole."
},
{
"question": "Is your Brexpiprazole suitable for R&D studies?",
"answer": "We support both R&D and commercial-scale Brexpiprazole production."
},
{
"question": "How does Brexpiprazole work as an antipsychotic?",
"answer": "It acts as a partial agonist at D2/5-HT1A receptors and antagonist at 5-HT2A receptors."
},
{
"question": "Can Brexpiprazole cause akathisia?",
"answer": "The risk is significantly lower compared with other dopamine partial agonists."
},
{
"question": "Is Brexpiprazole suitable for combination therapies?",
"answer": "Yes, particularly effective as augmented therapy with antidepressants."
}
]