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Taka Masao

@takamasao.bsky.social

160 followers 670 following 240 posts

Let's Flood Bluesky with Science! | Pharmaceutical scientist & science blogger

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Reposted by Taka Masao

Nature Reviews Drug Discovery @natrevdrugdiscov.nature.com · Jul 7

The changing landscape of medicinal chemistry optimization www.nature.com/articles/s41...
rdcu.be/evaV5

This new article analyses oral drug candidates and their corresponding hit and lead compounds from recent years and from the early 2000s, and discusses the implications of the observed trends

Trends for oral drug candidates

Taka Masao @takamasao.bsky.social · Jul 4

Predicted 1,633 human proteins as potential CRBN molecular glue targets, far broader than expected. Discovered helical G-loops as a new recognition motif. Demonstrated VAV1 can engage CRBN without G-loop structure through molecular surface mimicry.

Science:
www.science.org/doi/10.1126/...

Mining the CRBN target space redefines rules for molecular glue–induced neosubstrate recognition

The CRL4CRBN E3 ubiquitin ligase is the target of molecular glue degrader compounds that reprogram ligase specificity to induce the degradation of clinically relevant neosubstrate proteins. Known cere...

www.science.org

Taka Masao @takamasao.bsky.social · Jun 27

Prime editor-based high-throughput screening reveals functional synonymous mutations in human cells

Nature Biotechnology
www.nature.com/articles/s41...

Prime editor-based high-throughput screening reveals functional synonymous mutations in human cells - Nature Biotechnology

A prime editor screen systematically identifies deleterious synonymous variants in human cells.

Taka Masao @takamasao.bsky.social · Jun 19

Fully computational design achieves Kemp eliminase efficiency of 12,700 M⁻¹s⁻¹ without experimental optimization. Surpasses previous designs by 2 orders of magnitude. Final variant reaches 10⁵ M⁻¹s⁻¹, matching natural enzyme performance.😲

Nature: www.nature.com/articles/s41...

Complete computational design of high-efficiency Kemp elimination enzymes - Nature

We present a computational approach to the design of high-efficiency enzymes with catalytic parameters comparable to natural enzymes, enabling programming of stable, high-efficiency, new-to-nature Kem...

Taka Masao @takamasao.bsky.social · Jun 19

JNJ-6640: First-in-class PurF inhibitor demonstrates nanomolar bactericidal activity against M. tuberculosis. Targets de novo purine biosynthesis pathway, showing in vivo efficacy in mouse models.

Nature: www.nature.com/articles/s41...

Targeting de novo purine biosynthesis for tuberculosis treatment - Nature

The validation of inhibitors targeting PurF, a novel drug target for tuberculosis drug discovery, is described.

Taka Masao @takamasao.bsky.social · Jun 19

R9AP identified as common EBV receptor for both epithelial & B cell infection. R9AP binds directly to viral gH/gL complex, mediating membrane fusion. AMMO1 antibody blocks this interaction, suggesting therapeutic potential.

Nature: www.nature.com/articles/s41...

R9AP is a common receptor for EBV infection in epithelial cells and B cells - Nature

R9AP is a key receptor for entry of Epstein–Barr virus into human epithelial and B cells, and interacts directly with the viral glycoprotein gH/gL complex to mediate virus–host membrane fusion.

Taka Masao @takamasao.bsky.social · Jun 19

moPepGen: Graph-based algorithm achieves linear-time generation of non-canonical peptides from genomic variants, RNA fusions & circularization. Outperforms existing tools, enabling detection of 53.7% more peptides in cancer proteomes.

NatBiotech: www.nature.com/articles/s41...

Identification of non-canonical peptides with moPepGen - Nature Biotechnology

moPepGen enables the detection of peptides across species, proteases and technologies.

Taka Masao @takamasao.bsky.social · Jun 19

FRα identified as novel lysosome-trafficking receptor for targeted protein degradation. Polyvalent FRTACs achieve subnanomolar potency against membrane proteins. PD-L1-targeting FRTAC demonstrates robust degradation in vivo & reprograms TME in mice.

NatChemBio: www.nature.com/articles/s41...

Polyvalent folate receptor-targeting chimeras for degradation of membrane proteins - Nature Chemical Biology

Xiao, Dong, Xie, Feng et al. developed FRα-targeting chimeras (FRTACs) for targeted membrane protein degradation by conjugating multiple folate molecules to antibodies of targeted proteins. The folate...

Taka Masao @takamasao.bsky.social · Jun 19

PSC patients show expanded T & B cell responses against EBV epitopes compared to controls. Analysis of 116M+ health records reveals infectious mononucleosis increases PSC risk (OR=12). This suggests EBV may play a role in autoimmune liver disease pathogenesis

NatMed: www.nature.com/articles/s41...

T and B cell responses against Epstein–Barr virus in primary sclerosing cholangitis - Nature Medicine

Interrogation of electronic health records and the B and T cell repertoires of people with PSC shows a link between Epstein–Barr virus and primary sclerosing cholangitis, an incurable autoimmune liver...

Taka Masao @takamasao.bsky.social · Jun 19

LucaOne: First AI model to unify DNA, RNA & protein language. Trained on 169K+ species, it demonstrates emergent understanding of genetic translation without explicit training. Outperforms specialized tools across multiple tasks.

Nature Machine Intelligence: www.nature.com/articles/s42...

Generalized biological foundation model with unified nucleic acid and protein language - Nature Machine Intelligence

He and colleagues develop LucaOne, a biological foundation model pre-trained on nucleic acid and protein sequences from 169,861 species. It shows an emerging understanding of molecular biology’s centr...

Taka Masao @takamasao.bsky.social · Jun 6

"Is taurine an aging biomarker?"
Longitudinal data from humans, monkeys, and mice show circulating taurine does not decline with age. High individual variability and context-dependent health links limit its utility as an aging biomarker.

Science: www.science.org/doi/10.1126/...

Is taurine an aging biomarker?

Low circulating taurine concentrations have been proposed as a driver of the aging process. We found that circulating taurine concentrations increased or remained unchanged with age in three geographi...

www.science.org

Taka Masao @takamasao.bsky.social · Jun 4

CREM, a transcriptional repressor induced by CAR and IL-15 signaling via the PKA–CREB axis, limits CAR-NK effector function. Genetic ablation enhances anti-tumor activity and resistance to suppression, identifying CREM as a targetable intracellular checkpoint.

Nature: www.nature.com/articles/s41...

CREM is a regulatory checkpoint of CAR and IL-15 signalling in NK cells - Nature

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeri...

Taka Masao @takamasao.bsky.social · Jun 4

A blood-based DNA methylation “IC clock” predicts mortality and tracks decline in intrinsic capacity across five domains—cognition, mobility, vitality, sensory, and psychological. Strongly linked to immune aging and lifestyle factors.

Nature Aging: www.nature.com/articles/s43...

A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors - Nature Aging

Fuentealba and colleagues build and validate a DNA methylation clock of intrinsic capacity (IC) to bridge resource-intensive clinical assessments of IC with molecular readouts of aging, highlighting s...

Taka Masao @takamasao.bsky.social · Jun 4

Exosome-enriched glycoRNAs carry internal GalNAc modifications and resist RNase, suggesting glycosylation marks RNA for export. Disruption of protein glycosylation impairs glycoRNA trafficking.

Nature Cell Biology: www.nature.com/articles/s41...

Taka Masao @takamasao.bsky.social · Jun 4

Loss of PD-1 in Treg cells triggers a compensatory coinhibitory network centered on CD30, promoting stronger immune suppression through STAT5 activation and potentially undermining the efficacy of PD-1-based immunotherapy.

Nature Immuno: www.nature.com/articles/s41...

PD-1 receptor deficiency enhances CD30+ Treg cell function in melanoma - Nature Immunology

Here the authors show that PD-1 controls coinhibitory receptor expression by Treg cells. The absence of PD-1 expression could induce CD30 expression, thereby enhancing Treg function and tumor escape, ...

Taka Masao @takamasao.bsky.social · Jun 4

n a phase 2 trial, CIS43LS showed durable protection (87.4% efficacy at 40 mg/kg) against submicroscopic Plasmodium infection by qRT-PCR, highlighting mAb-based prophylaxis as a tool for malaria control.

Nature Medicine: www.nature.com/articles/s41...

Anti-sporozoite monoclonal antibody for malaria prevention: secondary efficacy outcome of a phase 2 randomized trial - Nature Medicine

A single dose of the anti-sporozoite monoclonal antibody CIS43LS can achieve durable, sterile protection against Plasmodium falciparum infection.

Taka Masao @takamasao.bsky.social · Jun 4

Rentosertib, a first-in-class TNIK inhibitor discovered by generative AI, improved forced vital capacity and showed favorable safety in a phase 2a IPF trial. A milestone for AI-driven drug discovery, linking de novo target identification.

Nature Medicine: www.nature.com/articles/s41...

A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial - Nature Medicine

Preliminary results from a phase 2a trial involving 71 patients suggest that a new agent, discovered and designed with artificial intelligence assistance, is safe and effective for the treatment of id...

Taka Masao @takamasao.bsky.social · Jun 4

Ketogenic diet or β-hydroxybutyrate administration halts Plasmodium development and protects mice from malaria. Mechanism: NAD depletion and transcriptional repression of virulence genes in the parasite. A metabolic strategy for malaria resistance.

Nature metabolism: www.nature.com/articles/s42...

β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice - Nature Metabolism

A ketogenic diet and the ketone body β-hydroxybutyrate are shown to confer resistance to malaria in mice by inducing metabolic reprogramming in Plasmodium parasites, suggesting a dietary strategy for ...

Taka Masao @takamasao.bsky.social · Jun 4

Cysteine depletion drives adipose browning and rapid weight loss via SNS–β3AR signaling, even without UCP1. In obese mice, this triggers 30% weight loss and reverses inflammation. A potential non-canonical path for therapeutic thermogenesis.

Nature metabolism: www.nature.com/articles/s42...

Cysteine depletion triggers adipose tissue thermogenesis and weight loss - Nature Metabolism

The authors describe how reduced dietary availability and systemic loss of cysteine leads to adipose tissue browning and rapid weight loss in mice and humans.

Taka Masao @takamasao.bsky.social · Jun 4

HSV-1 counteracts APOBEC1 by phosphorylating its uracil-DNA glycosylase, protecting its genome in neurons. Inhibiting this pathway via AAV-UGI protects against encephalitis, suggesting a new route for antiviral intervention.

Nature Microbiology: www.nature.com/articles/s41...

Herpes simplex virus 1 evades APOBEC1-mediated immunity via its uracil-DNA glycosylase in mice - Nature Microbiology

The herpes simplex virus 1 uracil-DNA glycosylase counters host APOBEC1 to evade genome editing and to enable viral replication that promotes encephalitis in mice.

Taka Masao @takamasao.bsky.social · Jun 4

Cancer therapy resistance is shaped by dynamic, co-evolving genetic and non-genetic processes. ARTNet researchers propose a next-gen framework using spatial omics, lineage tracing, and functional models to anticipate and overcome resistance.

Nature Reviews Cancer: www.nature.com/articles/s41...

Acquired resistance in cancer: towards targeted therapeutic strategies - Nature Reviews Cancer

Acquired therapeutic resistance is a key contributor to cancer treatment failure, requiring new approaches to address its complex mechanisms. In this Roadmap, Soragni, Knudsen and colleagues discuss t...

Taka Masao @takamasao.bsky.social · Jun 2

The CHALLENGE trial demonstrates that post-chemotherapy structured exercise significantly improves survival in resected colon cancer patients—5-year DFS up by 6.4%, 8-year OS up by 7.1%. Landmark level 1 evidence for exercise as a therapeutic modality.

NEJM: www.nejm.org/doi/full/10....

Structured Exercise after Adjuvant Chemotherapy for Colon Cancer | NEJM

Preclinical and observational studies suggest that exercise may improve cancer outcomes. However, definitive level 1 evidence is lacking. In this phase 3, randomized trial conducted at 55 centers, ...

Taka Masao @takamasao.bsky.social · May 28

Skeletal muscle proteome and phosphoproteome stratify insulin sensitivity better than clinical diagnosis. Despite sex-based metabolic differences, insulin-resistant signatures are conserved. AMPKγ3 S65 phosphorylation emerges as a potential muscle-specific target.

Cell: www.cell.com/cell/fulltex...

Personalized molecular signatures of insulin resistance and type 2 diabetes

Muscle samples from over 120 people were analyzed to identify molecular patterns linked to insulin resistance, a key feature of type 2 diabetes. The findings reveal new insights that could help tailor...

Taka Masao @takamasao.bsky.social · May 28

Systematic analysis of multicellular coordination across tissues shows dynamic, age- and state-dependent cell modules. In cancer, the coordination is rewired—healthy ecosystems collapse, and a universal tumor ecosystem emerges.

Nature: www.nature.com/articles/s41...

Cross-tissue multicellular coordination and its rewiring in cancer - Nature

Comprehensive single-cell transcriptomic analysis of 35 human tissues reveals 12 cross-tissue coordinated cellular modules that exhibit intramodule communication and dynamic changes with ageing, and w...

Taka Masao @takamasao.bsky.social · May 28

Leveraging early postnatal HSPC trafficking, in vivo lentiviral gene therapy achieves durable correction in mouse models of inherited disorders. Fanconi anaemia showed near-complete reconstitution due to selective advantage of edited cells.

Nature: www.nature.com/articles/s41...

In vivo haemopoietic stem cell gene therapy enabled by postnatal trafficking - Nature

In vivo gene delivery to haematopoietic stem and progenitor cells in newborn mice using engineered lentiviral vectors shows promise as an effective treatment for genetic diseases.