Paltusotine is a selective, orally active somatostatin receptor type 2 (SSTR2) agonist developed for the treatment of acromegaly. It is a synthetic, non-peptide small-molecule pharmaceutical active ingredient and was approved by the U.S. FDA on September 25, 2025 under the trade name Palsonify. FDA indicates Palsonify for adults with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.
PubChem lists paltusotine as C₂₇H₂₂F₂N₄O, molecular weight 456.5 g/mol and CAS 2172870-89-0. Paltusotine hydrochloride is separately identified as C₂₇H₂₃ClF₂N₄O, with molecular weight approximately 492.9 g/mol and CAS 2361216-83-1.
Paltusotine is a highly selective agonist of somatostatin receptor 2 (SSTR2). FDA pharmacology data describe more than 4,000-fold selectivity for SSTR2 compared with other somatostatin receptor subtypes. Activation of SSTR2 suppresses secretion of growth hormone (GH) from the pituitary gland and consequently decreases circulating insulin-like growth factor-1 (IGF-1).
In a human SSTR2 functional assay, paltusotine inhibited cyclic AMP accumulation with an average EC₅₀ of 0.25 nM, demonstrating potent receptor-mediated pharmacological activity.
Paltusotine is approved for the treatment of adults with acromegaly who have had an inadequate response to surgery or for whom surgery is not an option. It provides an oral alternative to injectable somatostatin receptor ligand therapies.
The approved product is Palsonify, supplied as film-coated tablets containing paltusotine hydrochloride equivalent to 20 mg or 30 mg of paltusotine. The 20 mg tablet contains 21.6 mg paltusotine hydrochloride, while the 30 mg tablet contains 32.4 mg paltusotine hydrochloride.
The recommended starting dose is 40 mg once daily, with titration to 60 mg once daily after 2–4 weeks based on IGF-1 levels.
Paltusotine is a relatively lipophilic small molecule with an XlogP value of approximately 5.3 and a calculated topological polar surface area of 86.2 Ų. PubChem reports no defined or undefined atom or bond stereocenters for the free-base structure, meaning the molecule does not have a conventional stereochemical purity requirement arising from a chiral center.
The compound contains fluorinated aromatic functionality, a quinoline core, an aminopiperidine group and a hydroxyl-substituted benzonitrile moiety. Its chemical structure supports oral bioavailability and selective SSTR2 receptor binding.
Paltusotine is a synthetic small-molecule API, so conventional pharmaceutical analytical techniques such as UHPLC/HPLC, UV identification, related-substance analysis, residual-solvent testing, water determination and elemental-impurity assessment are applicable.
FDA's 2025 chemistry review confirms that the drug product uses UHPLC-UV for identification and UHPLC for assay and impurity testing. However, the numerical acceptance criteria for assay and impurities in the FDA review are redacted. Therefore, those values should not be guessed or copied from a research-grade certificate of analysis and represented as an official API release specification.
FDA's quality review concluded that the CMC package met applicable standards for the identity, strength, quality and purity of the drug product.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |