X-165: A Potent, Bioavailable Autotaxin Inhibitor
X-165
potent, bioavailable autotaxin inhibitor orally active in fibrosis mod., Ph. I IND cleared from 225M cmpd DNA-encoded library + opt. J. Med. Chem., Jul. 23, 2020 X-Chem, Waltham, MA
Other molecules you may be interested in
MORF-627
Morphic Therapeutic’s MORF-627 is an oral αvβ6 integrin inhibitor designed to treat IPF by blocking the TGFβ pathway. The Morphic team leveraged SBDD and FEP+ during lead optimization to enhance permeability and isoform selectivity. This article highlights the team’s focus on inhibiting the “bent-closed” conformation of αvβ6 as well as the linker design that led to the “chameloenicity” of the lead compound. The impressive multispecies PK and in vivo efficacy of MORF-627 in preclinical models was unfortunately accompanied by oncogenic toxicity that prevented it from reaching clinical trials.
CC-90001
CC-90001 was nominated by reviewer Christian Kuttruff . CC-90001 is a JNK (c-Jun N-Terminal Kinase) inhibitor and a Phase II clinical candidate for idiopathic pulmonary fibrosis ( NCT03142191 ). Christian says, “Preclinical evidence suggests that c-Jun N-terminal kinase (JNK) enzyme function is required for key steps in the pulmonary fibrotic [...]
BMS986278
This month’s cover molecule, BMS-986278 , is an LPA 1 antagonist and oral (up to 125 mg BID) Ph. II clinical candidate for idiopathic pulmonary fibrosis (IPF) (NCT04308681). Reviewer and nominator Christian Kuttruff says: “While there are two approved molecules for the treatment of IPF (pirfenidone from Roche and nintedanib from BI), there is [...]
CHF-6366
Context. CHF-6366 (Chiesi Farmaceutici S.p.A) is a muscarinic antagonist and β2 agonist (MABA) being developed as an inhaled treatment for respiratory diseases. Muscarinic antagonists and β2 agonists both act to inhibit bronchoconstriction, but through different mechanisms, making the combination of both agents a desirable strategy for [...]
ziritaxestat
Ziretaxestat, an oral autotaxin (ATX) inhibitor originated by Galapagos, once garnered excitement as the first molecule to complete a Ph. III clinical program in idiopathic pulmonary fibrosis since the approvals of nintedanib and pirfenidone. Following the disappointing clinical data and discontinuation of the molecule, this annotation revisits ziritaxestat in the context of other inhibitors, recaps the therapeutic hypothesis and how it was discovered, summarizes notable molecular properties for drug discovery scientists, and discusses what happened and what’s next.
