Mutated Huntingtin (HTT) protein is the cause of Huntington’s disease (HD). HTT-D3 is an oral, CNS-penetrant molecule with human HTT lowering activity in vivo used to illustrate the science around PTC Therapeutics’ Huntingtin’s disease program. PTC had filed patent applications for the HD program as early as November 2016 ( WO201700726 ). PTC [...]

“compound 18” is an oral inducer of fetal hemoglobin (HbF) intended to treat anemias such as sickle cell disease and beta-thalassemia. The authors identified a weak hit (>10 uM) from a high-throughput phenotypic screen using human umbilical cord blood-derived erythroid progenitor cells. Optimization led to the azaspiro[3.3]heptane-containing [...]

The Pfizer CFTR potentiator, CP-628006 , enhances CFTR function in cystic fibrosis patient-derived airwell cells with a distinct mechanism of action from existing potentiators such as ivacaftor. It has a unique chemical structure, and in contrast to other potentiators does not seem to inhibit the channel at high concentrations of drug and [...]

Voxelotor is a first-in-class, reversible covalent aldehyde drug that prevents the hemoglobin polymerization, a primary driver of sickle cell disease. Approved in 2019 , this molecule represented a scientific milestone as a modern example of a reversible covalent drug being approved in a chronic indication. It is the first oral drug that [...]

Toward an oral, once-daily non-peptide STT2 agonist. Paltusotine a novel oral somatostatin receptor 2 (SST2) agonist and Crinetics’ lead investigational drug, is intended to treat acromegaly and neuroendocrine tumors (NETs) in carcinoid syndrome. Both diseases have been treated with surgery and injectable somatostatin [...]