LY-2584702

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H19F4N7
Molecular Weight	445.4161
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=C(N=C1C2CCN(CC2)C3=C4C=NNC4=NC=N3)C5=CC=C(F)C(=C5)C(F)(F)F

InChI

InChIKey=FYXRSVDHGLUMHB-UHFFFAOYSA-N

InChI=1S/C21H19F4N7/c1-31-10-17(13-2-3-16(22)15(8-13)21(23,24)25)29-19(31)12-4-6-32(7-5-12)20-14-9-28-30-18(14)26-11-27-20/h2-3,8-12H,4-7H2,1H3,(H,26,27,28,30)

HIDE SMILES / InChI

Molecular Formula	C21H19F4N7
Molecular Weight	445.4161
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24440085
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24456794

LY2584702 is a potent, highly selective adenosine triphosphate (ATP) competitive inhibitor against p70 S6 kinase, a downstream component of the phosphatidylinositol-3-kinase signalling pathway which regulates cell proliferation and survival. LY2584702 underwent clinical trials against solid tumors both as a monotherapy and in combination with erlotinib or everolimus. No responses were observed for treatment as a single agent. LY2584702 was not well tolerated when administered with erlotinib, therefore this combination is not feasible. The combination with everolimus was better tolerated but yielded very limited clinical benefit.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ribosomal protein S6 kinase 1 4 Target ID: CHEMBL4501 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24456794	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24456794	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1518.04 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2529.26 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
841.58 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1843 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	300 mg 1 times / day single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
6106.05 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13718.79 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4470.57 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
30897 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	300 mg 1 times / day single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24440085	300 mg 1 times / day single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LY-2584702 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	unhealthy, 61.5 n = 2 Health Status: unhealthy Condition: Cancer Age Group: 61.5 Sex: M+F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	DLT: Vomiting, Nausea... Dose limiting toxicities: Vomiting (grade 3, 50%) Nausea (grade 3, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871
100 mg 1 times / day multiple, oral MTD Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	unhealthy, 61.5 n = 3 Health Status: unhealthy Condition: Cancer Age Group: 61.5 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871
75 mg 2 times / day multiple, oral MTD Dose: 75 mg, 2 times / day Route: oral Route: multiple Dose: 75 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	unhealthy, 61.5 n = 3 Health Status: unhealthy Condition: Cancer Age Group: 61.5 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871

AEs

AE	Significance	Dose	Population
Nausea	grade 3, 50% DLT	300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	unhealthy, 61.5 n = 2 Health Status: unhealthy Condition: Cancer Age Group: 61.5 Sex: M+F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871
Vomiting	grade 3, 50% DLT	300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871	unhealthy, 61.5 n = 2 Health Status: unhealthy Condition: Cancer Age Group: 61.5 Sex: M+F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/24440085 Page: p.871

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34273	https://www.001chemical.com/chem/search?q=DY34273
001 Chemical	DY34274	https://www.001chemical.com/chem/search?q=DY34274
1PlusChem LLC	1P008U34	https://www.1pchem.com/search?query=1P008U34
AK Scientific	X3564	https://aksci.com/item_detail.php?cat=X3564
AbovChem LLC	HY-12493B	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-12493B
Angene	AGN-PC-0WCU12	http://www.angenechemical.com/productshow/AGN-PC-0WCU12.html
ApexBio Technology	B5815	https://www.apexbt.com/catalogsearch/result/?q=B5815
AstaTech	40963	http://astatechinc.com/CPSResult.php?CRNO=40963
AstaTech	C14145	http://astatechinc.com/CPSResult.php?CRNO=C14145
Axon MedChem	2464	https://www.axonmedchem.com/product/2464
BLD Pharm	BD303979	http://www.bldpharm.com/search/Search.html?keyword=BD303979
BLD Pharm	BD629884	http://www.bldpharm.com/search/Search.html?keyword=BD629884
BLD Pharm	BD629885	http://www.bldpharm.com/search/Search.html?keyword=BD629885
BOC Sciences	1082949-67-4	http://www.bocsci.com/description.asp?cas=1082949-67-4
Cayman Chemical	15320	http://www.caymanchem.com/app/template/Product.vm/catalog/15320
Chem Scene	CS-3597	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3597
ChemShuttle	134398	https://www.chemshuttle.com/catalogsearch/result/?q=134398
ChemShuttle	152064	https://www.chemshuttle.com/catalogsearch/result/?q=152064
Debye Scientific	DA-47982	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-47982
Excenen	EX-A2213	http://www.excenen.com/searchresultlist.php?id=EX-A2213
Excenen	EX-A534	http://www.excenen.com/searchresultlist.php?id=EX-A534
Matrix Scientific	153980	http://www.matrixscientific.com/153980.html
MedChem Express	HY-12493A	https://www.medchemexpress.com/search.html?q=HY-12493A&ft=&fa=&fp=
MolPort	MolPort-035-944-322	https://www.molport.com/shop/molecule-link/MolPort-035-944-322
MolPort	MolPort-035-944-331	https://www.molport.com/shop/molecule-link/MolPort-035-944-331
Molcore	MC34273	http://www.molcore.com/CatMC34273.html
Molcore	MC34274	http://www.molcore.com/CatMC34274.html
Molnova	M10327	https://www.molnova.com/en/serch-list.html?keywords=M10327
MuseChem	I000362	https://www.musechem.com/product/I000362.html
Ryan Scientific	ML_161	https://ryansci.com/products?q=ML_161&list_q=&search_type=exact
Selleck Chemicals	S7698	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7698
Selleck Chemicals	S7704	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7704
ShangHai Biochempartner	BCP001380	http://www.biochempartner.com/search_BCP001380
ShangHai Biochempartner	BCP001797	http://www.biochempartner.com/search_BCP001797
ShangHai Biochempartner	BCP14038	http://www.biochempartner.com/search_BCP14038
ShangHai Biochempartner	BCP15576	http://www.biochempartner.com/search_BCP15576
ShangHai Biochempartner	BCP15580	http://www.biochempartner.com/search_BCP15580
TargetMol	T6159	https://www.targetmol.com/search?keyword=T6159
Toronto Research Chemicals	L503100	https://www.trc-canada.com/product-detail/?CatNum=L503100
eMolecules	301217562	https://orderbb.emolecules.com/search/#?query=301217562
eMolecules	50550736	https://orderbb.emolecules.com/search/#?query=50550736
eMolecules	50550737	https://orderbb.emolecules.com/search/#?query=50550737
eMolecules	50550829	https://orderbb.emolecules.com/search/#?query=50550829
eMolecules	95706139	https://orderbb.emolecules.com/search/#?query=95706139
eNovation Chemicals	D501903	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501903&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4256187591	https://mcule.com/MCULE-4256187591/
mcule	MCULE-4679418434	https://mcule.com/MCULE-4679418434/
mcule	MCULE-5032551256	https://mcule.com/MCULE-5032551256/

PubMed

Title	Date	PubMed
A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours.	2014 Mar	24456794
A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours.	2014 Mar	24440085

Patents

Sample Use Guides

In Vivo Use Guide

LY2584702 tosylate was administered orally in a dose-escalating regime starting with 25 mg QD. The MTD was determined to be 75 mg BID or 100 mg QD.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:03:23 GMT 2023` Edited by `admin` on `Sat Dec 16 10:03:23 GMT 2023`
Record UNII	I4965C6W4O
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LY-2584702

Common Name

English

LY2584702

Code

English

LY 2584702

Code

English

1H-PYRAZOLO(3,4-D)PYRIMIDINE, 4-(4-(4-(4-FLUORO-3-(TRIFLUOROMETHYL)PHENYL)-1-METHYL-1H-IMIDAZOL-2-YL)-1-PIPERIDINYL)-

Systematic Name

English

Code System Code Type Description

DRUG BANK

DB12690