PMADS

Id:	acc1885
Group:	2sens
Protein:	p70s6K
Gene Symbol:	RPS6KB1
Protein Id:	P23443
Protein Name:	KS6B1_HUMAN
PTM:	phosphorylation
Site:	Thr389
Site Sequence:	SQFDSKFTRQTPVDSPDDSTL
Disease Category:	Cancer
Disease:	Colorectal Cancer
Disease Subtype:
Disease Cellline:	HT29
Disease Info:
Drug:	PD98059 + rapamycin
Drug Info:	"PD98059 is a non-ATP competitive MEK inhibitor with an IC50 of 2 μM, specifically inhibiting MEK-1-mediated MAPK activation without directly suppressing ERK1 and ERK2. rapamycin: -"
Effect:	modulate
Effect Info:	Drug therapy reduces the phosphorylation level and inhibits tumors.
Note:	drug comb
Score:	4.0
Pubmed(PMID):	19194827
Sentence Index:	19194827_2-3
Sentence:	"Here, we found that combination treatment with PD98059 and rapamycin suppressed the proliferation of CRC cells, induced apoptosis, arrested cell cycle, and reduced the incidence and volume of CRC in mice, as well as inhibited phosphorylation of mTOR and the MEK signal pathway components, of which the effects were more significant than single-drug treatments. These findings indicate that PD98059 combined with rapamycin appears to be a promising strategy for inhibiting the initiation, and progression of CRC, which may provide a novel strategy for CRC prevention."

Sequence & Structure:

MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVGPYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKKTIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLESVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
RPS6KB1	TAS0612	Ribosomal protein S6 kinase (P70S6K) inhibitor	1	Recruiting	neoplasm	ClinicalTrials
RPS6KB1	MSC-2363318A	Ribosomal protein S6 kinase (P70S6K) inhibitor	1	Completed	neoplasm	ClinicalTrials
RPS6KB1	LY-2780301	Ribosomal protein S6 kinase (P70S6K) inhibitor	1	Completed	lymphoma	ClinicalTrials
RPS6KB1	XL-418	Ribosomal protein S6 kinase (P70S6K) inhibitor	1	Suspended	neoplasm	ClinicalTrials
RPS6KB1	LY-2584702	Ribosomal protein S6 kinase 1 inhibitor	1	Terminated	renal cell carcinoma	ClinicalTrials
RPS6KB1	LY-2584702	Ribosomal protein S6 kinase 1 inhibitor	1	Terminated	non-small cell lung carcinoma	ClinicalTrials
RPS6KB1	LY-2584702	Ribosomal protein S6 kinase 1 inhibitor	1	Terminated	metastasis	ClinicalTrials
RPS6KB1	LY-2780301	Ribosomal protein S6 kinase (P70S6K) inhibitor	1	Completed	metastasis	ClinicalTrials
RPS6KB1	LY-2584702	Ribosomal protein S6 kinase 1 inhibitor	1	Terminated	neuroendocrine neoplasm	ClinicalTrials
RPS6KB1	LY-2584702	Ribosomal protein S6 kinase 1 inhibitor	1	Completed	cancer	ClinicalTrials
RPS6KB1	LY-2584702	Ribosomal protein S6 kinase 1 inhibitor	1	Terminated	cancer	ClinicalTrials
RPS6KB1	XL-418	Ribosomal protein S6 kinase (P70S6K) inhibitor	1	Suspended	cancer	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

RPS6KB1-Thr389
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
T	389	P	Liver cancer	Phosphorylation	23537100

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb