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PMS2 inhibitor NP1867 cysteinome adduction by cell-based proteomincs

ABSTRACT: MMR protein PMS2 is a druggable target. Discovery and characterisation of first-in-class small molecule MMR pathway modulator NP1867.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Alexia Hervieu

LAB HEAD: Rob Howes,

PROVIDER: PXD077673 | Pride | 2026-04-28

REPOSITORIES: Pride

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			Action	DRS
	20231009_NeoPhore_cysteinome_0p5uM_1_PRM.raw	Raw
	20231009_NeoPhore_cysteinome_0p5uM_2_PRM.raw	Raw
	20231009_NeoPhore_cysteinome_0p5uM_3_PRM.raw	Raw
	20231009_NeoPhore_cysteinome_0p5uM_4_PRM.raw	Raw
	20231009_NeoPhore_cysteinome_0p5uM_5_PRM.raw	Raw

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Publications

Pharmacological inhibition of PMS2 induces MMR deficiency and response to immune checkpoint blockade.

Blagg Julian J Riou Philippe P Hervieu Alexia A Piumatti Eleonora E Rodriguez-Plata Maria T MT Battuello Paolo P Peall Adam A Amodio Vito V Vitiello Pietro Paolo PP Nightingale Daniel J H DJH Bago Ruzica R Tongue Paige P Slater Tessa T Parmar Kalpesh K Patel Pradip P Rodríguez González Javier J Clark David E DE Langley Gareth W GW Nichols Charles C Guarne Alba A Winship Paul C M PCM Baker Matthew M Drysdale Martin M Germano Giovanni G Bardelli Alberto A

Cancer discovery 20260421

DNA mismatch repair (MMR) detects and corrects post-replicative DNA alterations; it is deregulated in up to 20% of human cancers. MMR-deficient (MMR-d) cancers display increased tumour mutational burden (TMB), microsatellite instability (MSI) and are eligible for checkpoint inhibitor (CPI) immunotherapy which commonly elicits durable responses. We reasoned that pharmacological blockade of MMR could broaden the patient population eligible for immunotherapy. Here we reveal MMR protein PMS2 as a dr ...[more]

PMID: 42013405

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An integrated chemoproteomic and screening platform identifies a functional and ligandable non-catalytic cysteine in caspase-2

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2025-01-14 | PXD046269 | Pride

A nabelschnur-localized high mobility group box-like protein is responsible for the proper segregation of the kinetoplast in Trypanosoma brucei

Project description:The kinetoplast (k), a distinctive arrangement of mitochondrial DNA found in trypanosomatid protists, comprises a concatenated network of minicircles and maxicircles that undergo division and segregation once during each cell cycle. Despite the identification and characterization of numerous proteins involved in kDNA replication and segregation, several critical steps in the segregation mechanism remain poor understood on the molecular level. One such step is the formation of the nabelschnur, a filamentous structure found in Trypanosoma brucei that connects the daughter kDNA networks prior to their complete segregation. In this study, we elucidate the characteristics of TbNAB70, a high mobility group box-like protein found to be localized to the nabelschnur and the kDNA disk, thereby representing the second protein identified within this cryptic structure. Our findings demonstrate that TbNAB70 is critical for the segregation, but not replication, of kDNA. Furthermore, structural predictions suggest the protein holds the capacity to bind to kDNA, illuminating the exact molecular mechanism involved. Thus, we propose that TbNAB70 plays a pivotal role in mediating the segregation of daughter kDNA networks.

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The extracellular proteome of two Bifidobacterium strains reveals different adaptation strategies to low iron conditions

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QIQ1-dependent bicarbonate-sensing in trypanosomes

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