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molecules of the month

TAK-906

peripherally-restricted D2/D3 antagonist

oral agent for gastroparesis in Ph. II

up to 100 mg PO BID

JPET, Clinical Pharmacology

Altos Therapeutics / Takeda, Cambridge

Chemical structure of TAK-906 Altos Therapeutics/Takeda D2/D3 receptor antagonist
2 mins read

The Altos Therapeutics/Takeda D2/D3 receptor antagonist, TAK-906, is a peripherally-restricted, non-BBB penetrant molecule, targeting the stomach and vomiting center in the area postrema to treat gastroparesis. Gastroparesis is a chronic condition characterized by delayed gastric emptying, resulting in nausea, vomiting, pain, and anorexia. Cisapride was used off-label in the past (but was famously withdrawn due to cardiac side effects). Metoclopramide, a dopamine receptor antagonist, is approved for short term use (up to 12 weeks) and up to 5 days by the EMA, due to the increased risk of tardive dyskinesia. Peripheral restriction was employed due to known CNS side effects of D2/D3 antagonism (e.g., tardive dyskinesia). It is a great example of a peripherally-restricted drug targeting a former CNS target in a new indication.…


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