PMADS

Id:	acc3538
Group:	2sens
Protein:	PDK4
Gene Symbol:	PDK4
Protein Id:	Q16654
Protein Name:	PDK4_HUMAN
PTM:	ubiquitination
Site:	unclear
Site Sequence:
Disease Category:	Immune system diseases
Disease:	Colitis
Disease Subtype:	Acute Severe Ulcerative Colitis
Disease Cellline:
Disease Info:
Drug:	Cyclosporine A (CsA)
Drug Info:	Cyclosporine A (CsA) is an immunosuppressive drug often used to prevent organ - rejection in transplant patients.
Effect:	modulate
Effect Info:	"Cyclosporine inhibits the ubiquitination of PDK4 by downregulating SIRT6, enhances glycolysis, and regulates neutrophil function to alleviate ASUC."
Note:
Score:	4.0
Pubmed(PMID):	33634990
Sentence Index:	33634990_7-8
Sentence:	"RESULTS: We found that HIF-1alpha expression and glycolysis significantly increased, while the release of IL-8, myeloperoxidase (MPO) and reactive oxygen species (ROS), the apoptosis, and ability of migration markedly decreased in neutrophils of ASUC patients who responded to CsA (Response group) compared with those who did not respond to CsA (Nonresponse group). We also observed that CsA-induced functional alternation of neutrophils was initiated through suppressing SIRT6 expression, which is responsible for expression of the downstream signaling molecules (e.g., HIF-1alpha, PFKFB3) and PDK4 ubiquitination, leading to fueling neutrophil glycolysis and TCA cycle."

Sequence & Structure:

MKAARFVLRSAGSLNGAGLVPREVEHFSRYSPSPLSMKQLLDFGSENACERTSFAFLRQELPVRLANILKEIDILPTQLVNTSSVQLVKSWYIQSLMDLVEFHEKSPDDQKALSDFVDTLIKVRNRHHNVVPTMAQGIIEYKDACTVDPVTNQNLQYFLDRFYMNRISTRMLMNQHILIFSDSQTGNPSHIGSIDPNCDVVAVVQDAFECSRMLCDQYYLSSPELKLTQVNGKFPDQPIHIVYVPSHLHHMLFELFKNAMRATVEHQENQPSLTPIEVIVVLGKEDLTIKISDRGGGVPLRIIDRLFSYTYSTAPTPVMDNSRNAPLAGFGYGLPISRLYAKYFQGDLNLYSLSGYGTDAIIYLKALSSESIEKLPVFNKSAFKHYQMSSEADDWCIPSREPKNLAKEVAM

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	3	Completed	lactic acidosis	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	3	Active, not recruiting	pyruvate dehydrogenase deficiency	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	2	Completed	head and neck squamous cell carcinoma	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	2	Recruiting	glioblastoma multiforme	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	2	Completed	glioblastoma multiforme	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	2	Completed	heart disease	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	2	Completed	lactic acidosis	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	2	Terminated	breast cancer	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	2	Terminated	lung cancer	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	1	Withdrawn	glioblastoma multiforme	ClinicalTrials
PDK4	SODIUM DICHLOROACETATE	Pyruvate dehydrogenase kinase inhibitor	1	Completed	pulmonary arterial hypertension	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No data.

PTM-Disease Association:

source: PTMD

No data.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb