If you’re here reading about drug discovery for fun, you’re probably a drug hunter. You might be someone on your way to a leadership role in pharma or biotech. Maybe you’re decades into your career and already leading an R&D division. You don’t have a PhD in drug hunting, and it’s unlikely to be in your job description. But something makes [...]

We've just published the final set of Molecules of the Month for 2021, and now it's time to nominate your favorite molecules for 2021's Molecules of the Year! Nominees should have either been first disclosed in 2021 or had a major new update in 2021 (e.g. clinical trial readout, publication, business transaction, approval). The molecule must [...]

Retinol-binding protein 4 (RBP4) is the sole carrier for retinol (vitamin A). It may also play a role in diabetes and reduction of RBP4 may be beneficial for the ocular disease AMD. Belite Bio had a Ph. III trial ongoing for an oral RBP4 antagonist (LBS-008, tinlarebant ) in Stargardt Disease and intends to start a Ph. III trial for AMD in [...]

MRTX1133 was nominated as December 2021’s cover molecule by reviewers Joachim Rudolph and Julien Lefranc . MRTX1133 is a non-covalent inhibitor of KRAS G12D that demonstrated tumor regression in a mouse xenograft model when dosed IP (maximum efficacy at 10-30 mg/kg, activity as low as 3 mg/kg). Joachim says, “The discovery of MRTX1133 [...]

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 [...]

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 [...]

Ulotaront (SEP-363856) is a Phase III candidate with FDA Breakthrough Therapy Designation for the treatment of schizophrenia with demonstrated efficacy based on a physician-rated scale (PANSS) in a 4-week placebo-controlled trial and continued improvement in an open-label extension study. Reviewer Jake Schwarz says, “ulotaront was developed [...]

Velsecorat (AZD7594) is an inhaled, non-steroidal glucocorticoid receptor modulator and antedrug (soft drug) for treatment of asthma and other respiratory conditions that has completed several Ph. II studies . While the paper states that the results support progression into Ph. III studies, a Ph. III study does not appear to have started and [...]

Vertex recently disclosed a CNS-penetrant ELOVL1 inhibitor, in which they described preclinical safety findings in rat and cyno. In this article, they disclose a structurally distinct series which displayed similar ocular toxicity in rat, and skin and CNS toxicities in cyno. A third structurally distinct series (undisclosed) also showed [...]

RP-3500 is an oral ATR kinase inhibitor and Ph. II clinical candidate for advanced solid tumors with ATRi-sensitizing mutations, alone or in combination with talazoparib (PARPi) or gemcitabine. Reviewer Anthony Vaganos says, “An ATR molecule ( ceralasertib ) is in clinical trials but studies in two different tumors in combination with PARP [...]

Gout is caused by the buildup of uric acid. The main treatments are drugs that increase uric acid secretion (uricosurics, e.g. probenecid ) and xanthine oxidase inhibitors which inhibit uric acid production (e.g. allopurinol ). URAT1 inhibitors like lesinurad (Ironwood Pharmaceuticals) and dotinurad are emerging treatments, inhibiting uric [...]

JAK kinases are now well-established targets in immunology, but the class has always had safety concerns hanging over it. The safety issues were exacerbated by a recent FDA decision to expand the black box warnings for the class for major cardiovascular events. Inhaled, lung-restricted JAK inhibitors have been of interest because they could [...]

Kinase inhibitors are increasingly being explored for diseases beyond cancer. While SGK1 has been a cancer target, SGK1 has also been implicated in osteoarthritis pathology, and the Sanofi team developed “compound 17a” to interrogate this. The starting point was identified from ligand-based virtual screening, focusing on the DFG-out [...]

Vanin-1 is a biotinidase (nitrilase superfamily) that hydrolyzes pantetheine. Despite the critical role of pantetheine, vanin-1 deficient mice don’t appear to have issues, but may be protected in inflammatory disease settings like IBD. Since human vanin-1 coverage requirements are unknown, the Pfizer vanin-1 program took a “no-regrets” [...]

LRRK2 is a target of interest for Parkinson’s disease (e.g. DNL-151 ), but development had been slowed by concerns about potential lung toxicity of LRRK2 inhibitors. A Phase I study of a LRRK2 inhibitor in healthy volunteers had not shown human toxicity, though, and Biogen/Denali plan to proceed with Ph. III and Ph. IIb trials in 2022 . The [...]

“Compound 25,” inhibits HPK1 via a rare “P-loop folded” active site conformation. The molecule was nominated by reviewer Julien Lefranc , and structural biologist Yoana Dimitrova shares some insight here: “The ‘folded P-loop’ conformation is considered “extremely unusual” – authors of a 2011 paper looked into this and found it in only 62 out [...]

New drugs are discovered by teams, not individuals. "Drug discovery is a complex undertaking, and I enjoy the collaboration with many people from different disciplines and expertise areas that it takes to solve this impossible puzzle," says reviewer Joachim Rudolph . Drug Hunter also takes a community to build, and we [...]

In 2022, Drug Hunter highlighted 120 Molecules of the Month with structures or stories that were published for the first time, were approved or disclosed new significant data. They were selected from tens of thousands of research articles published by leading institutions from around the world. Here is the final list of the top 10 candidates for 2022’s Molecule of the Year, nominated by our readers and reviewers. It's always incredibly hard to narrow down the group, and even harder to pick just one! These finalists are selected based on a variety of factors. There are four first-in-class compo...