Seladelpar is a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist developed as a targeted therapy for primary biliary cholangitis (PBC), a chronic cholestatic liver disease. Seladelpar is the active moiety of the pharmaceutical substance used in the approved product LIVDELZI. The active moiety has CAS No. 851528-79-5, molecular formula C₂₁H₂₃F₃O₅S, and molecular weight 444.50 g/mol. FDA and PubChem identify seladelpar as the R-configured single enantiomer.
For the approved pharmaceutical product, however, the drug substance is supplied as seladelpar lysine dihydrate, rather than as the free active moiety. FDA identifies seladelpar lysine as the lysine salt of seladelpar and describes the drug substance as a white to off-white solid. The API has the molecular formula C₂₁H₂₃F₃O₅S·C₆H₁₄N₂O₂·2H₂O and molecular weight 626.7 g/mol. The corresponding CAS number for seladelpar lysine dihydrate is 928821-40-3.
Seladelpar activates PPAR-δ, a nuclear receptor involved in lipid metabolism, inflammation and bile-acid homeostasis. Activation of PPAR-δ reduces expression of CYP7A1, an important enzyme involved in the synthesis of bile acids from cholesterol. Through this mechanism, seladelpar can reduce bile-acid synthesis and influence biochemical markers associated with PBC. FDA describes seladelpar as a PPAR-δ agonist and approved it for the treatment of PBC.
The U.S. FDA granted initial approval to LIVDELZI (seladelpar) on August 14, 2024. The approved indication is treatment of primary biliary cholangitis in adults who have had an inadequate response to ursodeoxycholic acid (UDCA), or as monotherapy in adults who cannot tolerate UDCA. The recommended dosage is 10 mg orally once daily.
The pharmaceutical substance has important physical and solid-state characteristics that should be considered during API manufacturing. FDA's chemistry review describes seladelpar lysine as a white to off-white solid with a reported melting point of 166.1°C, pKa of 3.20, and optical rotation of [α]D²⁵ = +18.3° on an anhydrous basis. The saturated aqueous solution has a reported pH of 7.3. The drug substance is slightly hygroscopic and can exhibit varying levels of hydration depending on relative humidity, while the commercial drug substance is manufactured as a dihydrate.
Solubility is also strongly dependent on the salt form and pH. FDA reports seladelpar lysine solubility greater than 74 mg/mL in water, greater than 136 mg/mL in N-methyl-2-pyrrolidone, greater than 77 mg/mL in 1,1,1,3,3,3-hexafluoro-2-propanol, greater than 65 mg/mL in trifluoroethanol, and greater than 36 mg/mL in dimethyl sulfoxide. The current product labeling states that the water solubility of seladelpar lysine dihydrate is pH-dependent, being slightly soluble at low pH and very soluble at high pH.
From an API manufacturing perspective, controlling the correct salt form, hydration state, stereochemical identity, purity and solid-state characteristics is particularly important. FDA states that the drug substance is produced under cGMP and released against a specification designed to assure its identity, strength, purity and quality throughout a 60-month assigned retest period. The approved drug substance also has a defined particle-size distribution, with FDA reporting approximately 2.323 µm (d10), 7.387 µm (d50) and 24.825 µm (d90).
For pharmaceutical manufacturing and B2B API supply, it is therefore important to distinguish Seladelpar (active moiety) from Seladelpar Lysine Dihydrate (the approved drug-substance form). Using the correct CAS number and molecular weight prevents confusion between the free active moiety and the pharmaceutical salt.
Seladelpar represents an important specialty API for liver-disease therapeutics, particularly PPAR-δ-targeted treatment of PBC. Its defined stereochemistry, lysine-dihydrate salt form and clinically established mechanism make it a specialized pharmaceutical ingredient requiring appropriate analytical, solid-state and stability controls.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Melting Point | 166.1°C |