PF-6870961 is a growth hormone secretagogue receptor 1a (GHSR1a) inverse agonist biased for inhibition of 𝜷-arrestin signaling, in contrast to its parent compound, PF-5190457, an unbiased GHSR1a inverse agonist. PF-6870961 was discovered as a major metabolite of [...]

A protein-protein interaction inhibitor for a challenging-to-drug master transcription factor. OICR12694 is an oral protein-protein interaction inhibitor targeting the challenging-to-drug oncogenic transcription factor, B cell lymphoma 6 (BCL-6) . As a master regulator of B cell differentiation in germinal centers and hence a common driver of [...]

What is it? MK-8189 is a Ph. II clinical candidate for schizophrenia targeting PDE10A, a long-pursued but uncracked target for psychosis. With potentially better target engagement over prior molecules, it could become the first in the class to demonstrate efficacy in this challenging therapeutic area. The discovery and medicinal chemistry [...]

Newly disclosed HIV-1 antiretroviral is the first integrase-LEDGF/p75 allosteric HIV-1 inhibitor to clear Ph. I safety trials. Biodim has recently disclosed a small molecule candidate, BDM-2 , that demonstrates nanomolar activity against HIV-1 replication in vitro and showed promising safety in healthy subjects in a 2020 Ph. I clinical trial [...]

What is it? GB0139 is a selective, inhaled inhibitor of galectin-3 and galectin-1 in Ph. II for IPF and COVID-19 pneumonitis, and is Galecto’s ($GLTO) lead asset. Galecto was founded in 2011 with Lund University academic galectin research leaders Ulf Nilsson and Hakon Leffler, and has had a research focus on galectin-3 modulators to treat [...]

What is it? Saridegib (IPI-926, patidegib) is a Smoothened receptor (SMO) antagonist and hedgehog pathway inhibitor currently in Ph. III trials for Gorlin syndrome. The molecule is a semisynthetic analog of the naturally-occuring SMO antagonist , cyclopamine, and has a long history and originates from Infinity Pharmaceuticals . After a [...]

Mirati’s “Breakthrough” KRAS G12C inhibitor, adagrasib, was granted accelerated approval by the FDA in 2022. As it follows Amgen’s first-in-class KRAS G12C inhibitor, sotorasib, adagrasib is constantly scrutinized for any evidence it may be different, or better, than sotorasib. This deep dive reviews the current understanding on how adagrasib [...]

Here’s a preview of two molecules acquired in January 2023 among 14 mentioned in this article: deuruxolitinib (CTP-543) This molecule, a deuterated version of JAK1/2 inhibitor ruxolitinib (Opzelura, Incyte), has received Breakthrough Therapy designation from the FDA and is being acquired by Sun Pharma via Concert in a $0.576B transaction [...]

We recently explored how the lipophilicity (logP) of drugs has changed over time and found that, on average, drugs have become more lipophilic through the decades, primarily attributable to the industry’s move away from natural products. Despite this shift, it is clear from a broad qualitative comparison of structures from past decades to [...]

Our latest roundup of small molecules in the news includes two potential upcoming approvals: rezafungin Rezafungin (CD-101) is a once-weekly IV antifungal agent and next-generation echinocandin (glucan synthase inhibitor) that demonstrated non-inferiority vs. standard of care caspofungin (IV QD) (NCT03667690). An FDA AdCom voted 14 to 1 in [...]

Two past Molecules of the Month inductees had significant updates recently, showing they’re still moving forward: upacicalcet This September ‘22 Molecule of the Month is an IV calcium-sensing receptor (CaSR) agonist first identified in flavor studies of peptides. It is already approved in Japan for secondary hyperparathyroidism (SHPT), and [...]

Our latest roundup of small molecules in the news includes three molecules moving into development for the first time: MRTX1133 Mirati’s reversible, long-acting KRASG12D inhibitor, and December ‘21 Molecule of the Month, is going into the clinic as an oral compound. While initial disclosures referred to its potential as an IV agent, Mirati [...]

In this update of small molecules in the news we will cover recent: (B/M)illion-Dollar Molecules: recent M&A’s, IPOs, and other fundraising Molecules in Motion: clinical trial updates and FDA filings Where Are They Now? updates on past Drug Hunter Molecules of the Month Potential Upcoming Approvals : recent NDA filings and upcoming PDUFA [...]

The final set of Molecules of the Month for 2022 is out, and now it’s time to nominate your favorite molecules for 2022’s Molecules of the Year! Nominees should have either been first disclosed in 2022 or had a major new update in 2022 (e.g. clinical trial readout, publication, business transaction, approval). The molecule must have a [...]

You can download our compilation of the 10 first-in-class large molecule drug approvals from 2022 below, which includes structural illustrations, drug targets and mechanisms of action, doses and routes of administration, and indication.

You can download our compilation of the 9 first-in-class small molecule drug approvals from 2022 below, which includes structures, drug targets and mechanisms of action, doses and routes of administration, and indication.

In 2022 there were 36 novel small molecule and large molecule drugs approved by the FDA, including 19 small molecule drug approvals. You can download our compilation of all 19 small molecule drug approvals from 2022 below, which includes structures, drug targets and mechanisms of action, doses and routes of administration, and indication. You [...]

A Merck HIV inhibitor with targeted cell-killing activity as a possible approach to finally eradicate HIV, a KIT-selective inhibitor with best-in-class potential for the treatment of GIST, a first-in-class dual ETA/AT1 antagonist recently approved for the rare kidney disease IgA nephropathy are just some of the examples for this month's MOTM. Learn more about the molecules by navigating to the full reviews on the right which cover: why the molecules matter, how they were discovered, the key steps behind optimization, how they work, why the targets were chosen, any interesting toxicology and cl...