Metabolite Tales Blog

JANUARY 26, 2023

Metabolism of 2022 FDA approved small molecule drugs – Part 1 Does CYP3A4 still rule? By Julia Shanu-Wilson It won’t come as much surprise to learn that of the 17 small molecules* approved by the FDA in 2022, CYP3A4 was the major player in drug metabolism. References Iversen et al., Front Pharmacol.,

Small Molecule 52

Small Molecule FDA Approval FDA Drugs 52

Dark Matter Blog

AUGUST 31, 2020

The majority of small molecule drugs induce their therapeutic effects by seeking out and binding to their intended target while avoiding most other molecules in the dense milieu of the cell interior. Our overall mission at Arrakis is to expand the set of “druggable” targets for small-molecule medicines to include RNA.

RNA 52

RNA Small Molecule Bioinformatics Computational Chemistry 52

Drug Hunter

JUNE 26, 2023

This article compiles recent high-profile clinical readouts and related news with small molecules of general interest and structures where they are available. Unlike sapropterin, sepiapterin is more active in cells and is also brain-penetrant.

Small Molecule 130

Small Molecule RNA Trials Treatment 130

DrugBank

MAY 22, 2024

Molecular dynamics (MD) simulations and other computational methods are vital tools in our arsenal , helping us peek into the atomic-level interactions and movements within the protein, helping reveal potential new binding sites induced by small molecule interactions. DNA and RNA are also key players, each bringing unique challenges.

Small Molecule 96

Small Molecule RNA DNA Pharmaceutical Companies 96

DrugBank

MAY 15, 2024

Researchers are experimenting with biologics—larger biological molecules that can do things small molecules can't, like targeting larger, more complex structures on cell surfaces or even inside cells. Understanding why these targets are resistant to current therapeutic strategies is crucial.

Small Molecule 98

Small Molecule Molecular Biology Drugs Disease 98

DrugBank

JULY 24, 2024

These multifunctional small molecules are like tiny spies, hijacking the body’s natural protein degradation system to remove unwanted proteins. Multifunctional Small Molecules and Peptides Beyond PROTACs, there are other exciting tools in the new drug discovery toolbox.

Small Molecule 98

Small Molecule Drugs Clinical Trials Therapies 98

Dark Matter Blog

JANUARY 16, 2023

We are moving rapidly toward escape velocity in our RNA expedition at Arrakis. For those of you joining us for the first time, it’s worth a quick look back at why we decided to go all-in on the RNA world, why people thought we were crazy, and why we know we’re not. Our terra firma is small-molecule medicines.

Small Molecule 52

Small Molecule RNA Drugs Disease 52

Drug Target Review

JULY 23, 2024

This laid the groundwork for my career in drug discovery using novel modalities like small molecule inhibitors, antibodies, RNA interference (RNAi) and, currently, small molecule protein degraders – which are opportunities to change how we think about medicines.

Small Molecule 116

Small Molecule Targeted Protein Degradation Science Disease 116

Drug Target Review

APRIL 7, 2025

Haemoglobin A1c (HbA1c) is a validated surrogate endpoint for the reduction of microvascular complications associated with diabetes mellitus; reduced HIV-RNA levels serve as an endpoint for HIV disease control; and a reduction in low-density lipoprotein (LDL) cholesterol is used as an endpoint indicating lower likelihood of cardiovascular events.

Clinical Development 59

Clinical Development Clinical Trials Clinical Pharmacology Trials 59

Dark Matter Blog

JUNE 21, 2023

Since our company’s founding in 2015, we have taken the long view and been singularly focused on building an extremely flexible and broadly applicable platform that can develop a host of RNA‑targeted small molecules (rSMs) to deliver precision medicines for dozens of targets that have been out of reach for conventional approaches.

Small Molecule 52

Small Molecule RNA Pharma Companies Science 52

LifeSciVC

JANUARY 16, 2024

Small molecule GLP1s? Small molecules are still in vogue despite IRA headwinds: We continue to hear optimism for the convenience of orals even in indications with high-commercial potential and enriched for CMS coverage (likely to fall in crosshairs of IRA).

Small Molecule 140

Small Molecule Trials Therapies Disease 140

Drug Target Review

SEPTEMBER 25, 2024

Applying our technology has enabled us to develop a new small molecule, TT125-802, and to assign a new role to the epigenetic regulator CBP/p300 as a novel master regulator of non-oncogene resistance. This orally available small molecule binds to the bromodomain of CBP/p300 in a highly specific manner.

Small Molecule 105

Small Molecule Therapies Regulations Treatment 105

Broad Institute

JUNE 30, 2023

The researchers also looked at the tool’s ability to detect changes in cellular phenotypes after exposure to drugs and small molecule compounds. That teaches us far more than looking for just a single informative data point.” Typically, studying drug therapies is an expensive and time-consuming undertaking.

Small Molecule 105

Small Molecule Cell Based Assays Disease Assay Development 105

Dark Matter Blog

JULY 16, 2021

As soon as I learned about DNA and RNA, I wanted to be a molecular biologist. Last stops at RNA My last roles in biotech were where my original passion began: DNA and RNA. My last stop at Arrakis Therapeutics is with a company targeting RNA with small molecules. Arrakis is the capstone of my career.

Small Molecule 52

Small Molecule RNA Clinical Trials DNA 52

Dark Matter Blog

JULY 19, 2021

However, in June I happened to attend the Gordon Research Conference on Chemical Biology and High-throughput Chemistry where I saw a session on small molecules and RNA. Making small-molecule drugs against RNA structures looked like a really cool problem – I want to do THAT! This is a thing?

RNA 52

RNA Small Molecule Science Therapies 52

The Pharma Data

JANUARY 19, 2021

In the paper, researchers from Johns Hopkins University and elsewhere found a natural long-form transactivating CRISPR RNA (tracr-L) in Streptococcus pyogenes that functions to downregulate its endogenous CRISPR-Cas9 system. But altering the tracr-L with genetic engineering to make it function more like a guide RNA increased CRISPR-Cas9 cuts.

Research 52

Research RNA Molecular Biology Small Molecule 52

Drug Target Review

DECEMBER 7, 2023

Researchers from the Laboratory of Bacteriology at The Rockefeller University have now found that bacteria sense phages by a defensive response named CBASS (cyclic oligonucleotide-based antiphage signalling system) which detects viral RNA. The novel, hairpin-shaped molecule was named cabRNA for CBASS-activating bacteriophage RNA.

RNA 59

RNA Immune Response DNA Molecular Biology 59

Dark Matter Blog

JULY 19, 2021

Or should I say back to retirement, as he was comfortably relaxing at home back in 2016 when Jen Petter lured him back into the fray with the siren call of developing a new class of RNA-targeted small-molecule medicines here at Arrakis. I won’t dwell on Jim’s many accomplishments here.

Small Molecule 52

Small Molecule RNA Science Therapies 52

Sygnature Discovery

JUNE 17, 2024

Our in-house SPR equipment comprises: 2x Biacore TM 8K+ 3x Biacore TM 8K 1x Biacore TM T200 This covers mM binders, such as fragments, through to sub pM interactions (such as late stage small molecules or very high affinity biological interactions, Tollenaere et al 2023 [link] ). This technology measures affinities from mM to nM.

Small Molecule 52

Small Molecule Fragment Screening DNA Science 52

The Pharma Data

OCTOBER 14, 2020

is a clinical-stage biopharmaceutical company developing novel RNA-modulating drug candidates (designed to be eukaryotic ribosomal selective glycosides) that are formulated to treat rare and ultra-rare premature stop codon diseases. Premature stop codons are point mutations that disrupt protein synthesis from messenger RNA.

Pharmaceuticals 52

Pharmaceuticals RNA Small Molecule Protein Production 52

Broad Institute

JUNE 21, 2023

Cell Painting uses six fluorescent dyes to image eight different components of a cell: the nucleus, nucleoli, mitochondria, endoplasmic reticulum (ER), golgi apparatus, cytoplasmic RNA, f-actin cytoskeleton, and plasma membrane. Typically, studying drug therapies is an expensive and time-consuming undertaking.

Small Molecule 52

Small Molecule Cell Based Assays Medical Schools Disease 52

The Pharma Data

DECEMBER 21, 2020

Galidesivir treatment was associated with a more rapid decline in viral RNA levels in the respiratory tract in an apparent dose-dependent manner. About Galidesivir (BCX4430) Galidesivir, a broad-spectrum antiviral drug, is an adenosine nucleoside analog that acts to block viral RNA polymerase.

Clinical Trials 52

Clinical Trials Virus RNA Trials 52

Sygnature Discovery

JUNE 17, 2024

Diverse Target Classes We Work With: Soluble Proteins: This includes kinases, ligases, transcription factors, helicases, polymerases, and DNA/RNA modifying enzymes, among others. Membrane Proteins: Examples include cell surface receptors, GPCRs, and transporters. Nucleic Acid Targets: Focusing on specific interactions and functions.

Biophysical Assays 52

Biophysical Assays Screening Hits Assay Development Fragment Screening 52

The Pharma Data

SEPTEMBER 9, 2020

Immunization of non-human primates (rhesus macaques) with BNT162b2, a nucleoside-modified messenger RNA (modRNA) candidate that expresses the SARS-CoV-2 spike glycoprotein, resulted in strong anti-viral effects against an infectious SARS-CoV-2 challenge.

Vaccine 52

Vaccine Clinical Trials RNA Trials 52

Drug Target Review

AUGUST 10, 2023

A twist of fate: GRP78 regulates cell migration and invasion Continuing their exploration of GRP78’s functions in the cell nucleus, the researchers utilised sophisticated RNA sequencing to compare lung cancer cells engineered to over-express nuclear GRP78 with cells lacking it.

Cell Biology 52

Cell Biology Small Molecule Regulations Engineering 52

The Pharma Data

MARCH 23, 2022

Back in 2018, researchers tested a broad-spectrum antiviral candidate called remdesivir/VEKLURY, which acts as a nucleotide decoy to get incorporated into the viral RNA genome and stop viral polymerase. But targeting Ebola virus polymerase has proven tough.

Virus 52

Virus Small Molecule Protein Production Research 52

Codon

JUNE 11, 2024

Their solution was to fuse hairpins, little loops made from RNA or DNA, at various positions along the DNA strand that was being sequenced. Small molecules can randomly transit through the pore and create disruptions, and the polymerase ratchet mechanism is imperfect, occasionally causing DNA to temporarily reverse direction through the pore.

DNA 87

DNA Engineering RNA Small Molecule 87

The Pharma Data

JANUARY 17, 2021

As Crooke explained, “With small molecules, if you make any chemical change, you have a new ballgame. That’s not the case with RNA-targeted drugs. “It’s the efficiency of antisense technology, coupled with its other characteristics, that makes n-Lorem’s approach feasible.”.

Disease 52

Disease Clinical Trials Small Molecule Treatment 52

Elrig

APRIL 29, 2024

She has played a key role inbuilding the target identification platform and a proprietary database of transcriptome-wide, functional RNA structures. There, I supported AI-enabled DD efforts in their small molecule portfolio.

Bioinformatics 59

Bioinformatics Drugs Molecular Biology Cell Based Assays 59

Alta Sciences

APRIL 17, 2024

Oligonucleotide-Based Techniques Most oligonucleotide therapies act through antisense mechanisms and are directed against various RNA species. Several small molecule GLP-1R agonists, such as oral orforglipron, are in late-stage clinical development.

Drug Development 52

Drug Development Treatment FDA Approval Drugs 52

Dark Matter Blog

AUGUST 27, 2020

A few years ago, at Arrakis Therapeutics, we set out to conquer a strange new territory, drugging RNA structures with small molecules. In fact, it was these early pharmaceutical successes that gave us the confidence that we would ultimately succeed in systematically drugging a wide range of RNA structures.

Small Molecule 52

Small Molecule RNA Clinical Trials Drugs 52

New Drug Approvals

SEPTEMBER 23, 2024

Target: DNA/RNA Synthesis Pathway: Cell Cycle/DNA Damage Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder of the brain, having symptoms characterized by involuntary movements, cognitive impairment, and mental deterioration. SCHEME PATENT PTC Therapeutics Inc., SCHEME PATENT PTC Therapeutics Inc.,

Small Molecule 57

Small Molecule RNA DNA Disease 57

Dark Matter Blog

APRIL 8, 2020

Most people, and in particular most investors we spoke to in those early days, thought we were nuts – that RNA lacked the structural and molecular complexity that medicinal chemistry exploits with such great effect for proteins. One is that molecular recognition is purely a matter of physics and RNA has to play by the same rules.

RNA 52

RNA Small Molecule Synthetic Chemistry Science 52

The Pharma Data

OCTOBER 21, 2020

AT-527 is expected to be ideally suited to combat COVID-19 as it inhibits viral replication by interfering with viral RNA polymerase, a key component in the replication machinery of RNA viruses. Importantly, the manufacturing process for our small molecule direct-acting antiviral allows us to produce AT-527 quickly and at scale.”.

RNA 52

RNA Pharmaceuticals Virus Clinical Trials 52

Drug Target Review

JULY 11, 2023

AI’s role in sequencing Bulk BCR RNA sequencing looks at specific B cells circulating in a blood sample that are producing these common antibodies. The challenge that we have using bulk BCR RNA,” she continued, “is that an antibody is made up of four components.

Disease 75

Disease RNA Small Molecule Clinical Development 75

The Pharma Data

MARCH 7, 2022

In their work, Levy and her colleagues focused on a complex of proteins called PRC2 that silences genes by attaching a small molecule, called a methyl group, to a protein that packages genes called histones. Cas9 binds and uses RNA as an address-tag. The AI-designed blocking protein was the cargo of the dCas9-RNA construct.

RNA 52

RNA DNA Packaging Small Molecule 52

Codon

APRIL 2, 2023

Read A new DNA polymerase variant, called RT-KTq I614Y, can directly detect RNA modifications, including pseudouridine (Ψ) and queuosine (Q). By combining this new variant with standard sequencing methods, it’s possible to identify RNA modifications in a really simple way. Nucleic Acids Research. Communications Biology.

DNA 52

DNA RNA Engineering Licensing 52