Industry News

Currently, the first-line drug for the treatment of PBC is ursodeoxycholic acid (UDCA), and the second-line drug obeticholic acid (OCA) has been withdrawn from the market due to efficacy issues. In 2024, the FDA approved the dual PPARα/δ agonist Elafibranor and the selective PPARδ agonist Seladelpar. Linerixibat is the first and currently the only drug specifically approved for pruritus in PBC. Other drugs mainly target disease progression or biochemical indicators, which provides more options for PBC patients.

Merck, in collaboration with Huanquan and Conquer Biotech, publicly disclosed the total synthesis of MK-0616, a first-in-class oral macrocyclic peptide PCSK9 inhibitor for cardiovascular disease. Facing structural complexity, the team developed a scalable route through multi-generation optimization—reducing steps from 63 to 43 and linear sequence from 28 to 21 steps. Key innovations include biocatalysis (KRED, TrpB, hydroxylase), crystallization-driven purification (avoiding chromatography), and orthogonal protecting group strategies. The second-generation process achieves nearly 1,000-fold yield improvement, enabling ton-scale production while significantly lowering costs, setting a benchmark for complex macrocyclic peptide synthesis.

The selection of chelating agents for targeted radionuclides is a precision science centered on matching the radionuclide, chelator, and targeting vector. Classic macrocyclic agents like DOTA offer exceptional stability for medium-sized radionuclides such as ¹⁷⁷Lu, and are used in approved drugs like Lutathera and Pluvicto. For larger α-emitting isotopes like ²²⁵Ac, novel chelators such as Macropa exhibit "reverse size selectivity" for superior complexation. Bifunctional design enables covalent linkage to antibodies or peptides, while high in vivo stability is critical for safety. Emerging research, including dual-size-selective chelators, is paving the way for integrated theranostic applications.

Eutectic technology is an innovative drug development strategy that optimizes the physicochemical properties of active pharmaceutical ingredients (APIs) without altering their chemical structure. By forming co-crystals with suitable ligands, this approach enhances solubility, stability, and bioavailability, enabling synergistic therapeutic effects and reducing toxicity. It also offers a practical pathway to bypass patent barriers, as co-crystals can qualify as novel entities for patent protection. Notably, the FDA may classify co-crystal products containing already-approved APIs as new dosage forms under Section 505(b)(2), potentially streamlining clinical trial requirements. Successful examples like Novartis’ Entresto demonstrate the technology’s substantial commercial potential.

This document profiles six key pharmaceutical peptide intermediates widely used in research and development: MOTS-C, BPC-157, Pinealon, Epitalon, TB-500, and GHK-Cu. Each entry covers the molecular formula, CAS number, and molecular weight, along with biological functions ranging from anti-aging and antioxidant effects to wound healing and insulin sensitivity improvement. The report also summarizes their original research origins, current clinical trial status, and standard synthesis methods, primarily solid-phase peptide synthesis (SPPS). These peptides represent a growing segment of biopharmaceutical research with potential therapeutic and cosmetic applications.