PMADS

Id:	acc3278
Group:	2sens
Protein:	SIRT1
Gene Symbol:	SIRT1
Protein Id:	Q96EB6
Protein Name:	SIR1_HUMAN
PTM:	phosphorylation
Site:	Ser649
Site Sequence:	NQYLFLPPNRYIFHGAEVYSD
Disease Category:	Nervous system diseases
Disease:	Alzheimer's Disease
Disease Subtype:
Disease Cellline:	N2aSwe?
Disease Info:
Drug:	Cilostazol + resveratrol
Drug Info:	"Cilostazol is a medication used to treat intermittent claudication by improving blood flow. \| Resveratrol is a natural compound with potential health benefits, including antioxidant and anti - inflammatory properties. "
Effect:	modulate
Effect Info:	"Cilostazol activates CK2α and promotes the phosphorylation of SIRT1, enhancing its deacetylation activity and thereby reducing the level of Ac-tau."
Note:
Score:	4.0
Pubmed(PMID):	24254769
Sentence Index:	24254769_1-2
Sentence:	"beta-Amyloid (Abeta) deposits and hyperphosphorylated tau aggregates are the chief hallmarks in the Alzheimer's disease (AD) brains, but the strategies for controlling these pathological events remain elusive. We hypothesized that CK2-coupled SIRT1 activation stimulated by cilostazol suppresses tau acetylation (Ac-tau) and tau phosphorylation (P-tau) by inhibiting activation of P300 and GSK3beta."

Sequence & Structure:

MADEAALALQPGGSPSAAGADREAASSPAGEPLRKRPRRDGPGLERSPGEPGGAAPEREVPAAARGCPGAAAAALWREAEAEAAAAGGEQEAQATAAAGEGDNGPGLQGPSREPPLADNLYDEDDDDEGEEEEEAAAAAIGYRDNLLFGDEIITNGFHSCESDEEDRASHASSSDWTPRPRIGPYTFVQQHLMIGTDPRTILKDLLPETIPPPELDDMTLWQIVINILSEPPKRKKRKDINTIEDAVKLLQECKKIIVLTGAGVSVSCGIPDFRSRDGIYARLAVDFPDLPDPQAMFDIEYFRKDPRPFFKFAKEIYPGQFQPSLCHKFIALSDKEGKLLRNYTQNIDTLEQVAGIQRIIQCHGSFATASCLICKYKVDCEAVRGDIFNQVVPRCPRCPADEPLAIMKPEIVFFGENLPEQFHRAMKYDKDEVDLLIVIGSSLKVRPVALIPSSIPHEVPQILINREPLPHLHFDVELLGDCDVIINELCHRLGGEYAKLCCNPVKLSEITEKPPRTQKELAYLSELPPTPLHVSEDSSSPERTSPPDSSVIVTLLDQAAKSNDDLDVSESKGCMEEKPQEVQTSRNVESIAEQMENPDLKNVGSSTGEKNERTSVAGTVRKCWPNRVAKEQISRRLDGNQYLFLPPNRYIFHGAEVYSDSEDDVLSSSSCGSNSDSGTCQSPSLEEPMEDESEIEEFYNGLEDEPDVPERAGGAGFGTDGDDQEAINEAISVKQEVTDMNYPSNKS

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	2	Completed	psoriasis	ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	2	Completed	type 2 diabetes mellitus	ClinicalTrials ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	1	Completed	chronic obstructive pulmonary disease	ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	1	Completed	psoriasis	ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	1	Completed	ulcerative colitis	ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	1	Completed	muscle atrophy	ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	1	Withdrawn	muscle atrophy	ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	1	Completed	Sepsis	ClinicalTrials
SIRT1	SRT-2104	NAD-dependent deacetylase sirtuin 1 activator	1	Completed	type 2 diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials 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 intensity data of this site,
show all other sites!

SIRT1-Ser27
Cancer	Intensity
BRCA
COAD	0.349
HGSC	-1.151
ccRCC
GBM
HNSC	0.737
LUAD
LUSC	1.034
non_ccRCC
PDAC	-0.969
UCEC

SIRT1-Ser47
Cancer	Intensity
BRCA	-1.634
COAD	-0.77
HGSC	0.479
ccRCC	0.468
GBM	0.233
HNSC	-0.167
LUAD	-1.117
LUSC	-0.264
non_ccRCC	2.169
PDAC	0.335
UCEC	0.269

SIRT1-Ser562
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC	-0.707

SIRT1-Ser615
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

SIRT1-Thr719
Cancer	Intensity
BRCA	0.116
COAD	-0.088
HGSC	-2.21
ccRCC	0.188
GBM	0.539
HNSC	0.446
LUAD	-0.63
LUSC	0.554
non_ccRCC	0.04
PDAC	1.81
UCEC	-0.767

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