July 28th Discovery of a New Class of Orexin 2 Receptor Agonists as a Potential Treatment for Narcolepsy https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5c00362 Abstract The orexinergic system, projecting from the lateral hypothalamus, operates through two receptors, orexin receptor type-1 (OX1) and orexin receptor type-2 (OX2), stabilizing wakefulness, mainly via OX2. Narcolepsy Type 1 (NT1) is characterized by excessive sleepiness and cataplexy, and is linked to a loss of orexin-producing neurons. Current therapies manage the symptoms but do not address…

Toxicology and Preclinical Testing (Animal Models) Today, I would like to share with you the story of another individual who made a remarkable contribution to the history of drug development. The person who laid the basis for modern preclinical animal model tox evaluations was Johann Wepfer (1620–1695).  A Swiss Pioneer of Toxicology and Preclinical Testing (Animal Models).  Long before modern drug development, Wepfer made groundbreaking strides in toxicological analysis. He is best known for his…

June 23rd Characterizing and understanding the formation of cysteine conjugates and other by-products in a random, lysine-linked antibody drug conjugate https://www.tandfonline.com/doi/full/10.1080/19420862.2021.1974150#abstract Abstract This study describes the characterization of conjugation sites for a random, lysine conjugated 2-iminothiolane (2-IT) based antibody-drug-conjugate synthesized from an IgG1 antibody and a duocarmycin analog-based payload-linker. Of the 80 putative lysine sites, 78 were found to be conjugated via tryptic peptide mapping and LC-HRMS. Surprisingly, seven cysteine-linked conjugated peptides were also detected…

May 12th Real Way to Target Gram-Negative Pathogens: Discovery of a Novel Helicobacter pylori Antibiotic Class https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5c00112 Abstract In an era of escalating antibiotic resistance, there is a pressing need for innovative strategies to develop novel antibiotics. Gram-negative bacteria, characterized by their robust dual-membrane, are intrinsically resistant to a wide range of antibiotics and can readily develop new resistances. Members of this bacterial class comprise numerous pathogenic organisms, including the primary cause of gastric cancer, Helicobacter pylori. In…

Dose Makes The Poison Today I’d like to tell you about a Swiss gentleman named Paracelsus.  Often called the “father” of modern toxicology and pharmacology, Paracelsus was the first to articulate a principle that still underpins toxicology today: “The dose makes the poison.” He argued that no substance is inherently toxic; it all depends on how much of it you take. Even substances we consider harmful can be beneficial in tiny amounts. Paracelsus famously used…

April 30th Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.4c02314 Abstract Oncogenic RAS mutations are among the most common in human cancers. To target the active, GTP-bound state of RAS(ON) directly, we employed an innovative tri-complex inhibitor (TCI) modality. Formation of a complex with an intracellular chaperone protein CypA, an inhibitor, and a target protein RAS blocks effector binding,…

Oldest Pharmacy Florence is world-renowned for its rich cultural heritage, home to Renaissance art, grand architecture, and literary giants like Dante Alighieri. Yet, tucked away in this treasure-filled city lies a lesser-known marvel: the oldest functioning pharmacy in the world. The Santa Maria Novella Pharmacy was founded in 1221 by a Dominican monk who began cultivating herbs to create medicinal balms, tinctures, and perfumes for their monastery and local patients. Officially opened to the public…

As 2025 approaches, the Molport team is looking back to say Thank You to our valued clients, partners, and all we’ve connected with in 2024! May 2025 be as refreshing as the scent of pine trees and as warm as cinnamon-spiced treats, filled with joy and success!   We look forward to continuing our work with you in 2025! The Molport Team

🎄 Holiday Notice! 🎄 In celebration of Christmas and New Year, Molport offices will be closed on December 24th, 25th, 26th & 31st and on January 1st. 🌟 As December is bustling with activity, our suppliers and couriers are working tirelessly to fulfill orders. To ensure timely delivery, we kindly encourage you to place your orders in advance. 📦 Please take a moment to review the shipment cutoffs for our major suppliers, as holiday schedules…

We are very pleased to introduce you to our new CEO, Diana Zelencova-Gopejenko, Ph.D.   Here, we find out a little bit more about Diana, including her medicinal chemistry expertise and how she plans to use her first-hand experience of the whole drug development cycle to both expand Molport’s current offering and introduce new, tailored MedChem tools to make sourcing diverse chemical compounds from around the world easier and faster.  By enhancing access to chemical compounds…