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Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML.

Cell chemical biology | 2019

The design of selective small molecules is often stymied by similar ligand binding pockets. Here, we report BSJ-03-123, a phthalimide-based degrader that exploits protein-interface determinants to achieve proteome-wide selectivity for the degradation of cyclin-dependent kinase 6 (CDK6). Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and transcriptomics and phosphoproteomics profiling of acute degradation of CDK6 enabled dynamic mapping of its immediate role in coordinating signaling and transcription.

Pubmed ID: 30595531 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P01 CA154303
  • Agency: NCI NIH HHS, United States
    Id: R01 CA214608
  • Agency: NCI NIH HHS, United States
    Id: R01 CA218278

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This is a list of tools and resources that we have found mentioned in this publication.


Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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GOrilla: Gene Ontology Enrichment Analysis and Visualization Tool (tool)

RRID:SCR_006848

A tool for identifying and visualizing enriched GO terms in ranked lists of genes. It can be run in one of two modes: * Searching for enriched GO terms that appear densely at the top of a ranked list of genes or * Searching for enriched GO terms in a target list of genes compared to a background list of genes.

View all literature mentions

STAR (tool)

RRID:SCR_015899

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

View all literature mentions

NetworkX (tool)

RRID:SCR_016864

Software Python package for the creation, manipulation, and study of the structure, dynamics, and functions of complex networks.

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STAR (tool)

RRID:SCR_004463

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

Anti-β-Actin Antibody (antibody)

RRID:AB_476744

This monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH

View all literature mentions

Phospho-Rb (Ser780) (D59B7) Rabbit mAb (antibody)

RRID:AB_10950972

This monoclonal targets Phospho-Rb (Ser780) (D59B7) Rabbit mAb

View all literature mentions

Rb (4H1) Mouse mAb (antibody)

RRID:AB_823629

This monoclonal targets Rb (4H1) Mouse mAb

View all literature mentions

Cdk6 (B-10) (antibody)

RRID:AB_627242

This monoclonal targets Human CDK6

View all literature mentions

CDK4 (D9G3E) Rabbit mAb (antibody)

RRID:AB_2631166

This monoclonal targets CDK4

View all literature mentions

MOLT-4 (cell line)

RRID:CVCL_0013

Cell line MOLT-4 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HT-29 (cell line)

RRID:CVCL_0320

Cell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MV4-11 (cell line)

RRID:CVCL_0064

Cell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MOLM-13 (cell line)

RRID:CVCL_2119

Cell line MOLM-13 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

P31/FUJ (cell line)

RRID:CVCL_1632

Cell line P31/FUJ is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Hs 578T (cell line)

RRID:CVCL_0332

Cell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

View all literature mentions

THP-1 (cell line)

RRID:CVCL_0006

Cell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Phospho-Rb (Ser780) (D59B7) Rabbit mAb (antibody)

RRID:AB_10950972

This monoclonal targets Phospho-Rb (Ser780) (D59B7) Rabbit mAb

View all literature mentions

MOLM-13 (cell line)

RRID:CVCL_2119

Cell line MOLM-13 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MV4-11 (cell line)

RRID:CVCL_0064

Cell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HT-29 (cell line)

RRID:CVCL_0320

Cell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MOLT-4 (cell line)

RRID:CVCL_0013

Cell line MOLT-4 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Anti-β-Actin Antibody (antibody)

RRID:AB_476744

This monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH

View all literature mentions

CDK4 (D9G3E) Rabbit mAb (antibody)

RRID:AB_2631166

This monoclonal targets CDK4

View all literature mentions

Cdk6 (B-10) (antibody)

RRID:AB_627242

This monoclonal targets Human CDK6

View all literature mentions

Rb (4H1) Mouse mAb (antibody)

RRID:AB_823629

This monoclonal targets Rb (4H1) Mouse mAb

View all literature mentions

Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

View all literature mentions

Hs 578T (cell line)

RRID:CVCL_0332

Cell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

THP-1 (cell line)

RRID:CVCL_0006

Cell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

P31/FUJ (cell line)

RRID:CVCL_1632

Cell line P31/FUJ is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions