PMADS

Id:	acc1390
Group:	2sens
Protein:	IN-R
Gene Symbol:	INSR
Protein Id:	P06213
Protein Name:	INSR_HUMAN
PTM:	phosphorylation
Site:	Tyr1146
Site Sequence:	IQMAAEIADGMAYLNAKKFVH
Disease Category:	Cancer
Disease:	Sarcoma
Disease Subtype:	Ewing Sarcoma
Disease Cellline:	JR1
Disease Info:
Drug:	SCH717454
Drug Info:	"SCH717454 (MK-3475), also known as pembrolizumab, is a humanized monoclonal antibody targeting the PD-1 receptor, used in immunotherapy for various cancers including melanoma and non-small cell lung cancer."
Effect:	modulate
Effect Info:	"SCH717454 can block IGF-1-stimulated Akt phosphorylation in sarcoma cells, but not IGF-2-stimulated Akt phosphorylation. SCH717454 also blocks both IGF-1-stimulated and IGF-2-stimulated IGF-1R phosphorylation, but does not block IGF-2-stimulated IN-R phosphorylation. Moreover, it blocks VEGF-stimulated HUVEC proliferation and tube formation, while exogenous IGF-2 and insulin circumvent these inhibitory effects."
Note:
Score:	4.0
Pubmed(PMID):	22188815
Sentence Index:	22188815_5-6
Sentence:	"SCH717454 blocked IGF-1-stimulated but not IGF-2-stimulated phosphorylation of Akt in sarcoma cells. Immunoprecipitation using anti-IGF-1R and anti-IN-R antibodies revealed that SCH717454 equally blocked IGF-1-stimulated and IGF-2-stimulated IGF-1R phosphorylation, but not IGF-2-stimulated phosphorylation of IN-R. SCH717454 completely blocked VEGF-stimulated proliferation and tube formation of HUVECs, but exogenous IGF-2 and insulin circumvented these inhibitory effects."

Sequence & Structure:

MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECLGNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQGCHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWERQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGTGAEDPRPSRKRRSLGDVGNVTVAVPTVAAFPNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSREKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSNPS

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
INSR	INSULIN ASPART	Insulin receptor agonist	4	Completed	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN GLARGINE	Insulin receptor agonist	4	-	diabetes mellitus	EMA ATC DailyMed DailyMed
INSR	INSULIN GLARGINE	Insulin receptor agonist	4	Terminated	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN GLULISINE	Insulin receptor agonist	4	-	diabetes mellitus	EMA DailyMed ATC
INSR	INSULIN PURIFIED BEEF	Insulin receptor agonist	4	-	diabetes mellitus	ATC ATC ATC ATC
INSR	INSULIN PURIFIED PORK	Insulin receptor agonist	4	-	diabetes mellitus	ATC ATC ATC ATC
INSR	INSULIN HUMAN	Insulin receptor agonist	4	Terminated	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN DETEMIR	Insulin receptor agonist	4	Completed	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN DETEMIR	Insulin receptor agonist	4	Terminated	diabetes mellitus	ClinicalTrials ClinicalTrials
INSR	INSULIN ASPART	Insulin receptor agonist	4	-	diabetes mellitus	DailyMed ATC DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed ATC
INSR	INSULIN ASPART	Insulin receptor agonist	4	Terminated	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN GLARGINE	Insulin receptor agonist	4	Completed	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN GLARGINE	Insulin receptor agonist	4	Unknown status	diabetes mellitus	ClinicalTrials
INSR	INSULIN GLARGINE	Insulin receptor agonist	4	Withdrawn	diabetes mellitus	ClinicalTrials ClinicalTrials
INSR	INSULIN LISPRO	Insulin receptor agonist	4	-	diabetes mellitus	DailyMed EMA ATC DailyMed DailyMed ATC DailyMed
INSR	INSULIN GLULISINE	Insulin receptor agonist	4	Completed	diabetes mellitus	ClinicalTrials
INSR	INSULIN HUMAN	Insulin receptor agonist	4	-	diabetes mellitus	DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed EMA ATC ATC DailyMed DailyMed ATC ATC ATC DailyMed DailyMed DailyMed
INSR	INSULIN HUMAN	Insulin receptor agonist	4	Completed	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN HUMAN	Insulin receptor agonist	4	Not yet recruiting	diabetes mellitus	ClinicalTrials
INSR	INSULIN HUMAN	Insulin receptor agonist	4	Recruiting	diabetes mellitus	ClinicalTrials ClinicalTrials ClinicalTrials
INSR	INSULIN HUMAN	Insulin receptor agonist	4	Unknown status	diabetes mellitus	ClinicalTrials
INSR	INSULIN HUMAN	Insulin receptor agonist	4	Withdrawn	diabetes mellitus	ClinicalTrials ClinicalTrials
INSR	INSULIN DETEMIR	Insulin receptor agonist	4	-	diabetes mellitus	ATC DailyMed DailyMed DailyMed EMA
INSR	INSULIN DEGLUDEC	Insulin receptor agonist	4	-	diabetes mellitus	DailyMed EMA ATC
INSR	INSULIN DEGLUDEC	Insulin receptor agonist	4	Terminated	diabetes mellitus	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

Residue	Position	State	Disease	Class	PMID
Y	1149	D	Diabetes mellitus	Phosphorylation	17272402
Y	1185	U	Neuroblastoma	Phosphorylation	24349301
Y	1189	U	Neuroblastoma	Phosphorylation	24349301

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