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Details

Stereochemistry ACHIRAL
Molecular Formula C19H17NO3
Molecular Weight 307.3432
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LY-294002

SMILES

O=C1C=C(OC2=C(C=CC=C12)C3=CC=CC=C3)N4CCOCC4

InChI

InChIKey=CZQHHVNHHHRRDU-UHFFFAOYSA-N
InChI=1S/C19H17NO3/c21-17-13-18(20-9-11-22-12-10-20)23-19-15(7-4-8-16(17)19)14-5-2-1-3-6-14/h1-8,13H,9-12H2

HIDE SMILES / InChI

Molecular Formula C19H17NO3
Molecular Weight 307.3432
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

LY294002 is a morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of phosphoinositide 3-kinases (PI3Ks). It was previously under active development by Eli Lily and was tested in a number of clinical cancer trials including neuroblastomas and head and neck cancer. However, commercialization efforts have been discontinued, and LY294002 is now predominantly used as a research tool.

Originator

Curator's Comment: # Eli Lilly

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P42336
Gene ID: 5290.0
Gene Symbol: PIK3CA
Target Organism: Homo sapiens (Human)
1.4 µM [IC50]
Target ID: P30542
Gene ID: 134.0
Gene Symbol: ADORA1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
1100 mg/m2 2 times / week multiple, intravenous (unknown)
Highest studied dose
Dose: 1100 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 1100 mg/m2, 2 times / week
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources:
Other AEs: hypersensitivity...
Other AEs:
hypersensitivity (grade 3, 11.1%)
Sources:
180 mg/m2 2 times / week multiple, intravenous (unknown)
Studied dose
Dose: 180 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 180 mg/m2, 2 times / week
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
DLT: diarrhoea...
Dose limiting toxicities:
diarrhoea (grade 3, 1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
hypersensitivity grade 3, 11.1%
1100 mg/m2 2 times / week multiple, intravenous (unknown)
Highest studied dose
Dose: 1100 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 1100 mg/m2, 2 times / week
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources:
diarrhoea grade 3, 1 pt
DLT
180 mg/m2 2 times / week multiple, intravenous (unknown)
Studied dose
Dose: 180 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 180 mg/m2, 2 times / week
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Involvement of p70 S6 kinase in bone morphogenetic protein signaling: vascular endothelial growth factor synthesis by bone morphogenetic protein-4 in osteoblasts.
2001
Evaluation of signal transduction pathways in chemoattractant-induced human monocyte chemotaxis.
2001 Apr
Dynamic changes of connexin-43, gap junctional protein, in outer layers of cumulus cells are regulated by PKC and PI 3-kinase during meiotic resumption in porcine oocytes.
2001 Apr
p110-related PI 3-kinases regulate phagosome-phagosome fusion and phagosomal pH through a PKB/Akt dependent pathway in Dictyostelium.
2001 Apr
Regulation of translation initiation by FRAP/mTOR.
2001 Apr 1
Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt.
2001 Apr 27
Activation of protein kinase A and atypical protein kinase C by A(2A) adenosine receptors antagonizes apoptosis due to serum deprivation in PC12 cells.
2001 Apr 27
alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity.
2001 Apr 27
The flightless I protein colocalizes with actin- and microtubule-based structures in motile Swiss 3T3 fibroblasts: evidence for the involvement of PI 3-kinase and Ras-related small GTPases.
2001 Feb
Il-4 and IL-13, but not IL-10, protect human synoviocytes from apoptosis.
2001 Feb 15
Stimulation of tetrahydrobiopterin synthesis induced by insulin: possible involvement of phosphatidylinositol 3-kinase.
2001 Jan
Growth factor-stimulated phosphorylation of Akt and p70(S6K) is differentially inhibited by LY294002 and Wortmannin.
2001 Jan
A role for PYK2 in regulation of ERK1/2 MAP kinases and PI 3-kinase by ANG II in vascular smooth muscle.
2001 Jan
Rac1 protects epithelial cells against anoikis.
2001 Jul 27
Antigen-receptor cross-linking and lipopolysaccharide trigger distinct phosphoinositide 3-kinase-dependent pathways to NF-kappa B activation in primary B cells.
2001 Jun
Regulation of ClC-2 chloride channels in T84 cells by TGF-alpha.
2001 Jun
Roles of Akt and glycogen synthase kinase 3beta in the ultraviolet B induction of cyclooxygenase-2 transcription in human keratinocytes.
2001 Jun 1
Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility.
2001 Jun 1
Rac1 activity is required for the activation of hypoxia-inducible factor 1.
2001 Jun 15
Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells: protective role in apoptosis.
2001 Jun 22
Phosphoinositide 3-kinase-dependent regulation of interleukin-3-induced proliferation: involvement of mitogen-activated protein kinases, SHP2 and Gab2.
2001 Jun 29
Roles of phosphatidylinositol 3-kinase and phospholipase D in temporal activation of superoxide production in FMLP-stimulated human neutrophils.
2001 Mar
Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia.
2001 Mar 23
Synergistic activation of RSK correlates with c-fos induction in MO7e cells stimulated with GM-CSF plus Steel factor.
2001 Mar 9
Role of phosphatidylinositol-3 kinase and its association with Gab1 in thrombopoietin-mediated up-regulation of platelet function.
2001 May
ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1.
2001 May
Reciprocal phosphorylation and regulation of endothelial nitric-oxide synthase in response to bradykinin stimulation.
2001 May 11
Gastrin-induced DNA synthesis requires p38-MAPK activation via PKC/Ca(2+) and Src-dependent mechanisms.
2001 May 4
Patents

Sample Use Guides

In an open-label Phase II clinical trial patients with recurrent or refractory advanced Squamous Cell Carcinoma of the Head and Neck with PIK3CA mutation received SF1126 (LY294002) intravenously twice per week at a dose of 1110 mg/m^2 in 28-day cycles with each dose separated by at least 3 days for the first 4 cycles followed by once per week in subsequent cycles.
Route of Administration: Intravenous
LNCaP (CRL-1740) and PC-3 (CRL-1435) human prostate carcinoma cells were cultured in RPMI-1640 medium or Ham's F12 K medium, respectively, supplemented with 10 % heat-inactivated fetal bovine serum, 1% antibiotic-antimycotic and incubated at 37 deg-C in a 5% CO2 atmosphere. LNCaP and PC-3 cells were plated in 6-well tissue culture plates at a concentration of 5 × 10^5 cells per well in complete growth medium for 32 h for LNCaP and 24 h for PC-3 and then sustained growth arrest in growth medium without FBS for 24 h. Cells were stimulated with TNF-α, IL-1β, IL-13, and IFN-γ with or without LY294002. Healthy cells generate a typical cell cycle histogram and the sub-G1 fraction represents the percentage of cell death. Flow cytometric quantification of apoptotic and viable cells with annexin V-FITCH/Propidium Iodide staining was also performed. Treatment of LNCaP cells with LY-294002 resulted in a statistically significant increase of cell death in comparison to control cells. Treatment of PC-3 cells with LY-294002 did not induce statistically significant alterations of cell death in comparison to control cells.
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:29:59 GMT 2023
Edited
by admin
on Sat Dec 16 08:29:59 GMT 2023
Record UNII
31M2U1DVID
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LY-294002
Common Name English
2-(4-MORPHOLINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE
Systematic Name English
NSC-697286
Code English
SF-1101
Code English
Code System Code Type Description
FDA UNII
31M2U1DVID
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
EPA CompTox
DTXSID6042650
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
PUBCHEM
3973
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
NSC
697286
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
DRUG BANK
DB02656
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
CAS
154447-36-6
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
NCI_THESAURUS
C148229
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
CHEBI
65329
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
WIKIPEDIA
LY294002
Created by admin on Sat Dec 16 08:29:59 GMT 2023 , Edited by admin on Sat Dec 16 08:29:59 GMT 2023
PRIMARY
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