Taka Masao
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takamasao.bsky.social
Taka Masao
@takamasao.bsky.social
160 followers 680 following 240 posts
Let's Flood Bluesky with Science! | Pharmaceutical scientist & science blogger
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takamasao.bsky.social
”kinase inhibitors are revealed to be frequent inducers of target degradation by 'supercharging' native proteolytic circuits”
Inhibitors supercharge kinase turnover through native proteolytic circuits
www.nature.com/articles/s41...
Inhibitors supercharge kinase turnover through native proteolytic circuits - Nature
Inhibitor-induced kinase degradation is a common event that positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.
www.nature.com
November 27, 2025 at 12:49 AM
Reposted by Taka Masao
nature.com
Nature research paper: NSD2 targeting reverses plasticity and drug resistance in prostate cancer

go.nature.com/3XmxA6v
NSD2 targeting reverses plasticity and drug resistance in prostate cancer - Nature
Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.
go.nature.com
November 26, 2025 at 7:23 PM
Reposted by Taka Masao
cellpress.bsky.social
"Stress-induced sympathetic hyperactivation drives hair follicle necrosis to trigger autoimmunity" spkl.io/63326Ad0f6

Ya-Chieh Hsu & colleagues
@cp-cell.bsky.social
Acute stress causes immediate hair follicle necrosis and hair loss via sympathetic nerves, which in turn activates and expand s autoreactive CD8 ⁺ T cells targeting hair follicles. Thus, a single stress event not only causes immediate tissue damage but also predisposes the tissue to future autoimmune attack.
November 26, 2025 at 11:30 PM
Reposted by Taka Masao
natrevdrugdiscov.nature.com
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
July 7, 2025 at 2:33 PM
takamasao.bsky.social
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
July 4, 2025 at 6:28 AM
takamasao.bsky.social
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.
www.nature.com
June 27, 2025 at 8:21 AM
takamasao.bsky.social
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...
www.nature.com
June 19, 2025 at 12:19 AM
takamasao.bsky.social
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.
www.nature.com
June 19, 2025 at 12:15 AM
takamasao.bsky.social
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.
www.nature.com
June 19, 2025 at 12:14 AM
takamasao.bsky.social
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.
www.nature.com
June 19, 2025 at 12:12 AM
takamasao.bsky.social
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...
www.nature.com
June 19, 2025 at 12:08 AM
takamasao.bsky.social
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...
www.nature.com
June 19, 2025 at 12:05 AM
takamasao.bsky.social
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...
www.nature.com
June 19, 2025 at 12:03 AM
takamasao.bsky.social
"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
June 6, 2025 at 7:39 AM
takamasao.bsky.social
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...
www.nature.com
June 4, 2025 at 11:51 PM
takamasao.bsky.social
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...
www.nature.com
June 4, 2025 at 11:51 PM
takamasao.bsky.social
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...
www.nature.com
June 4, 2025 at 11:49 PM
takamasao.bsky.social
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, ...
www.nature.com
June 4, 2025 at 11:47 PM
takamasao.bsky.social
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.
www.nature.com
June 4, 2025 at 11:45 PM
takamasao.bsky.social
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...
www.nature.com
June 4, 2025 at 11:43 PM
takamasao.bsky.social
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 ...
www.nature.com
June 4, 2025 at 11:38 PM
takamasao.bsky.social
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.
www.nature.com
June 4, 2025 at 11:34 PM
takamasao.bsky.social
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.
www.nature.com
June 4, 2025 at 11:31 PM
takamasao.bsky.social
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...
www.nature.com
June 4, 2025 at 11:29 PM
takamasao.bsky.social
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, ...
www.nejm.org
June 2, 2025 at 1:49 AM