Evidence map›Paper›PMID 41756985›Full record

ArticlebioRxiv : the preprint server for biology2026

A Scalable Design for Proximity-Inducing Molecules.

Endri Karaj, Varsha Venkatarangan, Shaimaa H Sindi, Surached Siriwongsup, Chaiheon Lee, Rajaiah Pergu, Vedagopuram Sreekanth, Karishma Kailass, Kien Tran, Prashant Singh and 13 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Endri KarajChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Varsha VenkataranganChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Shaimaa H SindiChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Surached SiriwongsupChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Chaiheon LeeChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rajaiah PerguChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Vedagopuram SreekanthChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Karishma KailassChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kien TranChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Prashant SinghChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Sameek SinghChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Junya KawaiChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jeffrey E FungChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mahilet TeferaChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rohil DhaliwalChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Santosh K ChaudharyChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
April KeyesChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ananthan SadagopanChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lisa BoatnerBiological Chemistry Department, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
Neel H ShahDepartment of Chemistry, Columbia University, New York, NY 10027.
Charlie FehlDepartment of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States.
Keriann M BackusBiological Chemistry Department, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
Amit ChoudharyChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Funding

UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Development of platforms for beta cell-specific delivery and ligand discoveryU01DK137242 · NIDDK · BROAD INSTITUTE, INC. · PI Amit Choudhary, ROHIT N. KULKARNI · 2023 to 2026
$3.9M
Probing tyrosine phosphatase structure and functionR35GM138014 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SHAH, NEEL H · 2020 to 2024
$2.3M
Chemical approaches for precision genome editingR01GM137606 · NIGMS · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT · 2021 to 2024
$1.5M
Development of phosphorylation editing chimeras using kinase inhibitorsR21AI178690 · NIAID · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT · 2024 to 2025
$462k
Development of phosphorylation-inducing chimeric small moleculesR21AI154099 · NIAID · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT · 2020 to 2021
$440k
Induced-Proximity Platform to Control Cellular Signaling and ProteostasisK99GM159057 · NIGMS · BROAD INSTITUTE, INC. · PI KARAJ, ENDRI · 2025 to 2025
$118k
NCI NIH HHS P50 CA211015NIAID NIH HHS R21 AI154099NIAID NIH HHS R21 AI178690NIDDK NIH HHS U01 DK137242NIGMS NIH HHS K99 GM159057NIGMS NIH HHS R01 GM137606NIGMS NIH HHS R35 GM138014
6 · The paper itself

Abstract

Chimeric molecules, which bring together an effector enzyme and a protein-of-interest (POI) to add/remove post-translational modifications (PTMs), are furnishing transformative modalities (e.g., PROTACs). However, these chimeras' scalability is limited as they employ rare, non-inhibitory binders of effectors. We report GRoup-transfer chimeras for Inducing Proximity (GRIPs) that employ abundantly available effectors' inhibitors to append POI binder on the effector using group-transfer handles. To demonstrate scalability, we develop 6 GRIPs classes for 3 PTMs utilizing diverse inhibitor, spanning 16 effector-POI pairs. Furthermore, we report a toolbox of 42 tunable group-transfer handles for Cys/Lys residues and ~5000 inhibitor-residue pairs for diverse effectors. Using global proteomics, we confirm the specificity for group transfer and PTM editing. GRIPs endowed new functionalities to POI drugs, including preventing rebound signaling upon drug withdrawal, a more potent/persistent inhibition, and inhibitor-induced pathway activation in 4 fully-endogenous systems. In diverse

Identifiers

PMID41756985
PMCPMC12934950

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.