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Compound Detail

CHEMBL362558

LY-2090314
🧪 Phase II
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🧪 Phase II
O=C1NC(=O)C(c2cnc3ccccn23)=C1c1cn2c3c(cc(F)cc13)CN(C(=O)N1CCCCC1)CC2

Basic Information

ChEMBL ID CHEMBL362558
Name LY-2090314
Phase Phase II
Structure Type MOL
InChI Key HRJWTAWVFDCTGO-UHFFFAOYSA-N

Known Names

Ly 2090314 Ly-2090314 LY2090314
44
Targets
60
Activities
2
Assay Types
30
PK Parameters
20
Publications
3
Known Names
3
Indications
2
Mechanisms

Molecular Properties

512.5
MW (Da)
3.42
ALogP
6
HBA
1
HBD
92.0
PSA (Ų)
0.42
QED
1
Ro5 Violations
2
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Extended Properties

Molecular Formula C28H25FN6O3
MW 512.55
Aromatic Rings 4
Heavy Atoms 38
NP-Likeness -1.17

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Glycogen synthase kinase-3 beta inhibitor INHIBITOR Glycogen synthase kinase-3 beta
Glycogen synthase kinase-3 alpha inhibitor INHIBITOR Glycogen synthase kinase-3 alpha

Indications

Leukemia Neoplasms Pancreatic Neoplasms

Activity Summary

IC50 36 meas. best 9.15
Ki 24 meas. best 6.6

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Glycogen synthase kinase-3 beta
CHEMBL262
IC50 9.15 9.01 0.7 6
Glycogen synthase kinase-3 alpha
CHEMBL2850
IC50 8.99 8.8767 1.0 3
SK-MEL-2
CHEMBL614917
IC50 8.22 8.22 6.0 1
M14
CHEMBL614317
IC50 8.15 8.15 7.0 2
Unchecked
CHEMBL612545
IC50 8.1 7.834 8.0 5
A2058
CHEMBL613503
IC50 8.1 8.1 8.0 1
A-375
CHEMBL613859
IC50 8.1 8.05 8.0 2
CHL-1
CHEMBL1075422
IC50 6.96 6.96 110.0 1
LNCaP
CHEMBL612518
IC50 6.82 6.82 150.0 1
Cyclin-dependent kinase 2
CHEMBL301
Ki 6.6 6.6 251.2 1
Tyrosine-protein kinase Lck
CHEMBL258
Ki 6.5 6.5 316.2 1
Protein kinase C beta type
CHEMBL3045
IC50 6.38 6.38 420.0 1
BXPC-3
CHEMBL614530
IC50 6.37 6.37 430.0 1
MDA-MB-468
CHEMBL614335
IC50 6.35 6.35 450.0 1
Serine/threonine-protein kinase 17A
CHEMBL4525
Ki 6.3 6.3 501.2 1
Dual specificity protein kinase CLK4
CHEMBL4203
Ki 6.2 6.2 631.0 1
5'-AMP-activated protein kinase catalytic subunit alpha-1
CHEMBL4045
Ki 6.2 6.2 631.0 1
Serine/threonine-protein kinase pim-1
CHEMBL2147
Ki 6.1 6.1 794.3 1
Serine/threonine-protein kinase N2
CHEMBL3032
Ki 6.1 6.1 794.3 1
Cyclin-dependent kinase 1
CHEMBL308
Ki 6.1 6.1 794.3 1
Dual specificity protein kinase CLK2
CHEMBL4225
Ki 6.0 6.0 1000.0 1
Cyclin-dependent kinase 5
CHEMBL4036
Ki 5.9 5.9 1258.9 1
Ribosomal protein S6 kinase alpha-3
CHEMBL2345
Ki 5.9 5.9 1258.9 1
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
CHEMBL2292
Ki 5.8 5.8 1584.9 1
MAP/microtubule affinity-regulating kinase 3
CHEMBL5600
Ki 5.8 5.8 1584.9 1
Cyclin-dependent kinase 4
CHEMBL331
IC50 5.75 5.75 1800.0 1
Protein kinase C gamma type
CHEMBL2938
Ki 5.6 5.6 2511.9 1
STE20-like serine/threonine-protein kinase
CHEMBL4202
Ki 5.6 5.6 2511.9 1
Cyclin-dependent kinase 2
CHEMBL301
IC50 5.55 5.55 2800.0 1
3-phosphoinositide-dependent protein kinase 1
CHEMBL2534
Ki 5.5 5.5 3162.3 1
Protein kinase C delta type
CHEMBL2996
Ki 5.5 5.5 3162.3 1
SRSF protein kinase 1
CHEMBL4375
Ki 5.5 5.5 3162.3 1
Calcium/calmodulin-dependent protein kinase type II subunit gamma
CHEMBL3829
Ki 5.5 5.5 3162.3 1
Serine/threonine-protein kinase 3
CHEMBL4708
Ki 5.4 5.4 3981.1 1
Calcium/calmodulin-dependent protein kinase type II subunit delta
CHEMBL2801
Ki 5.4 5.4 3981.1 1
DU-145
CHEMBL613508
IC50 5.26 5.26 5520.0 1
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
CHEMBL4766
IC50 5.21 5.21 6200.0 1
Calcium/calmodulin-dependent protein kinase type II subunit beta
CHEMBL4121
Ki 5.2 5.2 6309.6 1
Serine/threonine-protein kinase TAO1
CHEMBL5261
Ki 5.1 5.1 7943.3 1
Serine/threonine-protein kinase pim-3
CHEMBL5407
Ki 5.1 5.1 7943.3 1
NCI-H2030
CHEMBL1075530
IC50 5.03 5.03 9440.0 1
A549
CHEMBL392
IC50 5.0 5.0 9960.0 1
HCT-116
CHEMBL394
IC50 4.98 4.98 10480.0 1
COLO 205
CHEMBL614561
IC50 4.95 4.95 11300.0 1
NCI-H460
CHEMBL396
IC50 4.88 4.88 13250.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 3550.0 ng.hr.mL-1 Rattus norvegicus
AUC 216.0 ng.hr.mL-1 Homo sapiens
AUC 1870.0 ng.hr.mL-1 Homo sapiens
AUC 1570.0 ng.hr.mL-1 Homo sapiens
AUC 1790.0 ng.hr.mL-1 Rattus norvegicus
AUC 1260.0 ng.hr.mL-1 Rattus norvegicus
AUC 3227.0 ng.hr.mL-1 Canis lupus familiaris
AUC 15067.0 ng.hr.mL-1 Canis lupus familiaris
AUC 427.0 ng.hr.mL-1 Homo sapiens
AUC 976.0 ng.hr.mL-1 Homo sapiens
AUC 1600.0 ng.hr.mL-1 Homo sapiens
AUC 3310.0 ng.hr.mL-1 Homo sapiens
AUC 192.0 ng.hr.mL-1 Homo sapiens
AUC 404.0 ng.hr.mL-1 Homo sapiens
AUC 938.0 ng.hr.mL-1 Homo sapiens
AUC 1830.0 ng.hr.mL-1 Homo sapiens
AUC 2190.0 ng.hr.mL-1 Homo sapiens
CL 12.0 mL.min-1.kg-1 Rattus norvegicus
CL 41.3 L/hr Homo sapiens
CL 52.2 L/hr Homo sapiens
CL 38.3 L/hr Homo sapiens
CL 27.88 mL.min-1.kg-1 Canis lupus familiaris
CL 40.5 mL.min-1.kg-1 Rattus norvegicus
CL 57.5 mL.min-1.kg-1 Rattus norvegicus
CL 5.617 mL.min-1.kg-1 Canis lupus familiaris
CL 47.2 L/hr Homo sapiens
CL 46.9 L/hr Homo sapiens
CL 37.0 L/hr Homo sapiens
CL 44.8 L/hr Homo sapiens
CL 36.3 L/hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Glycogen synthase kinase-3 beta IC50 = 0.7 nM 9.15 Inhibition of Glycogen synthase kinase-3 beta dependent Tau protein serine-396 p... 15267232
Glycogen synthase kinase-3 beta IC50 = 0.9 nM 9.05 Inhibition of human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate m... 30925338
Glycogen synthase kinase-3 beta IC50 = 0.9 nM 9.05 Inhibition of GSK3beta (unknown origin) 23305709
Glycogen synthase kinase-3 alpha IC50 = 1.02 nM 8.99 Inhibition of human GSK-3alpha S449A mutant (2 to end residues) using phospho GS... 30925338
Glycogen synthase kinase-3 beta IC50 = 1.1 nM 8.96 Inhibition of human Glycogen synthase kinase-3 beta 15267232
Glycogen synthase kinase-3 beta IC50 = 1.1 nM 8.96 Inhibition of human GSK3-beta 18929433
Glycogen synthase kinase-3 beta IC50 = 1.29 nM 8.89 Inhibition of human GSK-3beta H350L mutant (2 to end residues) at 10 uM using ph... 30925338
Glycogen synthase kinase-3 alpha IC50 = 1.5 nM 8.82 Inhibition of GSK3alpha (unknown origin) 23305709
Glycogen synthase kinase-3 alpha IC50 = 1.5 nM 8.82 Inhibition of human GSK-3alpha using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate ... 30925338
SK-MEL-2 IC50 = 6.0 nM 8.22 Antiproliferative activity against human SK-MEL-2 cells harboring NRAS Q61R muta... 25915038
M14 IC50 = 7.0 nM 8.15 Antiproliferative activity against human M14 cells harboring BRAF V600E mutation... 25915038
M14 IC50 = 7.0 nM 8.15 Antiproliferative activity against human vemurafenib-resistant M14 cells harbori... 25915038
A2058 IC50 = 8.0 nM 8.1 Antiproliferative activity against human A2058 cells harboring BRAF V600E/PTEN n... 25915038
A-375 IC50 = 8.0 nM 8.1 Antiproliferative activity against human vemurafenib-resistant A-375 cells harbo... 25915038
Unchecked IC50 = 8.0 nM 8.1 Antiproliferative activity against human MEXF1341 cells harboring NRAS Q61 mutat... 25915038
A-375 IC50 = 10.0 nM 8.0 Antiproliferative activity against human A-375 cells harboring BRAF V600E mutati... 25915038
Unchecked IC50 = 11.0 nM 7.96 Antiproliferative activity against human MEL1102 cells harboring NRAS Q61K mutat... 25915038
Unchecked IC50 = 12.0 nM 7.92 Antiproliferative activity against human MEXF462 cells harboring BRAF V600E muta... 25915038
Unchecked IC50 = 14.0 nM 7.85 Antiproliferative activity against human MEXF276 cells harboring BRAF V600E muta... 25915038
Unchecked IC50 = 46.0 nM 7.34 Antiproliferative activity against human MEXF1792 cells harboring NRAS G13D muta... 25915038

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 U2OS 346
- 10.6019/CHEMBL4689842 Fibroblast 345
- 10.6019/CHEMBL4689842 HEK-293T 344
23305709 10.1124/dmd.112.048488 Homo sapiens 76
23305709 10.1124/dmd.112.048488 ADMET 32
23305709 10.1124/dmd.112.048488 Rattus norvegicus 18
23305709 10.1124/dmd.112.048488 Canis familiaris 17
25915038 10.1371/journal.pone.0125028 Glycogen synthase kinase-3 14
25915038 10.1371/journal.pone.0125028 A-375 11
25915038 10.1371/journal.pone.0125028 Unchecked 9
23305709 10.1124/dmd.112.048488 Plasma 8
25915038 10.1371/journal.pone.0125028 M14 6
15267232 10.1021/jm049768a ADMET 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
23305709 10.1124/dmd.112.048488 Nucleic Acid 4
30925338 10.1016/j.ejmech.2019.03.039 Glycogen synthase kinase-3 alpha 3
23305709 10.1124/dmd.112.048488 Molecular identity unknown 3
15267232 10.1021/jm049768a Rattus norvegicus 3
30925338 10.1016/j.ejmech.2019.03.039 Glycogen synthase kinase-3 beta 3
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2

Data from ChEMBL 36 via Core Engine