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Compound Detail

CHEMBL4071864

GSK2982772
🧪 Phase II
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🧪 Phase II
CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL4071864
Name GSK2982772
Phase Phase II
Structure Type MOL
InChI Key LYPAFUINURXJSG-AWEZNQCLSA-N

Known Names

Gsk2982772
9
Targets
43
Activities
4
Assay Types
20
PK Parameters
20
Publications
1
Known Names
5
Indications
1
Mechanisms

Molecular Properties

377.4
MW (Da)
1.55
ALogP
5
HBA
2
HBD
100.2
PSA (Ų)
0.72
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Unknown

Flags

Chemical Probe

Extended Properties

Molecular Formula C20H19N5O3
MW 377.40
Aromatic Rings 3
Heavy Atoms 28
NP-Likeness -0.87

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Receptor-interacting serine/threonine-protein kinase 1 inhibitor INHIBITOR Receptor-interacting serine/threonine-protein kinase 1 ✓ ✓

Indications

Arthritis, Rheumatoid Colitis, Ulcerative Psoriasis Immune System Diseases Inflammatory Bowel Diseases

Activity Summary

IC50 26 meas. best 9.4
EC50 11 meas. best 8.9
Kd 3 meas. best 7.31
Ki 3 meas. best 9.01

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Receptor-interacting serine/threonine-protein kinase 1
CHEMBL5464
 IC50 9.4 8.4875 0.4 12
Receptor-interacting serine/threonine-protein kinase 1
CHEMBL5464
 Ki 9.01 8.3667 1.0 3
U-937
CHEMBL612794
 EC50 8.9 8.9 1.3 1
HT-29
CHEMBL384
 EC50 8.56 8.4571 2.8 7
Mus musculus
CHEMBL375
 EC50 8.4 8.4 4.0 1
Unchecked
CHEMBL612545
 IC50 8.4 6.64 4.0 5
HT-29
CHEMBL384
 IC50 8.39 8.39 4.1 1
U-937
CHEMBL612794
 IC50 8.23 8.215 5.9 2
Receptor-interacting serine/threonine-protein kinase 1
CHEMBL5464
 Kd 7.31 7.28 49.0 3
Mus musculus
CHEMBL375
 IC50 6.0 5.75 1000.0 2
L929
CHEMBL612267
 EC50 5.9 5.9 1260.0 1
Receptor-interacting serine/threonine-protein kinase 1
CHEMBL3784911
 IC50 5.89 5.745 1300.0 2
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
 EC50 4.89 4.89 13000.0 1
Cytochrome P450 2C9
CHEMBL3397
 IC50 4.6 4.6 25000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2300.0 ng.hr.mL-1 Rattus norvegicus
AUC 2300.0 ng.hr.mL-1 Rattus norvegicus
AUC 2900.0 ng.hr.mL-1 Macaca fascicularis
AUC 2300.0 ng.hr.mL-1 Rattus norvegicus
CL 17.0 mL.min-1.kg-1 Rattus norvegicus
CL 10.0 mL.min-1.kg-1 Macaca fascicularis
Cmax 2146263.91 nM Rattus norvegicus
Cmax 1907790.14 nM Macaca fascicularis
F 110.0 % Rattus norvegicus
F 86.0 % Macaca fascicularis
Fu 0.042 - Rattus norvegicus
Fu 0.11 - Canis lupus familiaris
Fu 0.11 - Macaca fascicularis
Fu 0.074 - Homo sapiens
T1/2 3.9 hr Rattus norvegicus
T1/2 6.5 hr Macaca fascicularis
T1/2 1.867 hr Homo sapiens
T1/2 1.917 hr Homo sapiens
Tmax 0.25 hr Rattus norvegicus
Tmax 1.8 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Receptor-interacting serine/threonine-protein kinase 1 IC50 = 0.4 nM 9.4 Inhibition of RIP1 in human primary neutrophils assessed as reduction in TNFalph... 28151659
Receptor-interacting serine/threonine-protein kinase 1 IC50 = 0.5 nM 9.3 Inhibition of RIP1 in human primary neutrophils assessed as reduction in TNFalph... 28151659
Receptor-interacting serine/threonine-protein kinase 1 Ki = 0.9772 nM 9.01 Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluo... 29485864
Receptor-interacting serine/threonine-protein kinase 1 IC50 = 1.0 nM 9.0 Inhibition of RIP1 (unknown origin) in ADP-glo assay 36346971
Receptor-interacting serine/threonine-protein kinase 1 IC50 = 1.0 nM 9.0 Inhibition of pDEST8HisGSTTev-tagged human RIP1 (1 to 375 residues) expressed in... 31223438
Receptor-interacting serine/threonine-protein kinase 1 IC50 = 1.0 nM 9.0 Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected i... 28151659
U-937 EC50 = 1.27 nM 8.9 Anti-necroptosis activity against TSZ-induced human U-937 cells 38171150
Receptor-interacting serine/threonine-protein kinase 1 IC50 = 1.6 nM 8.8 Inhibition of RIP1 in human primary neutrophils assessed as reduction in TNFalph... 28151659
Receptor-interacting serine/threonine-protein kinase 1 Ki = 1.66 nM 8.78 Inhibition of human RIPK1 assessed as inhibition constant by ADP-Glo Kinase assa... 38316369
Receptor-interacting serine/threonine-protein kinase 1 IC50 = 2.0 nM 8.7 Inhibition of RIP1 in human whole blood assessed as reduction in TNFalpha/QCD-OP... 28151659
HT-29 EC50 = 2.78 nM 8.56 Anti-necroptosis activity against TSZ-induced human HT-29 cells 38171150
HT-29 EC50 = 2.9 nM 8.54 Anti-necroptic activity against human HT-29 cells assessed as cell viability pre... 38309200
HT-29 EC50 = 3.6 nM 8.44 Anti-necroptosis activity against human HT-29 cells assessed as inhibition of TS... 36724216
HT-29 EC50 = 3.6 nM 8.44 Anti-necroptotic activity in TSZ induced human HT-29 cells assessed as increase ... 36288088
HT-29 EC50 = 3.6 nM 8.44 Anti-necroptotic activity in human HT-29 cells assessed as inhibition of hTNFalp... 33930803
Mus musculus EC50 = 4.0 nM 8.4 Anti-inflammatory activity in imiquimod-induced BALB/c mouse psoriasis model ass... 38422702
Unchecked IC50 = 4.0 nM 8.4 Inhibition of RIP1 in cynomolgus monkey whole blood assessed as reduction in TNF... 28151659
HT-29 EC50 = 4.1 nM 8.39 Anti-necroptotic activity against TSZ induced necroptosis in human HT-29 cells p... 37364415
HT-29 IC50 = 4.1 nM 8.39 Induction of necroptosis in human HT-29 cells assessed as increase in TNFalpha/A... 29485864
HT-29 EC50 = 4.1 nM 8.39 Anti-necroptosis activity against human HT-29 cell assessed as inhibition of TSZ... 38484677

Literature References

PubMed DOI Target Context # Activities
28151659 10.1021/acs.jmedchem.6b01751 Unchecked 20
28151659 10.1021/acs.jmedchem.6b01751 ADMET 18
28151659 10.1021/acs.jmedchem.6b01751 Receptor-interacting serine/threonine-protein kinase 1 14
28151659 10.1021/acs.jmedchem.6b01751 Rattus norvegicus 9
28151659 10.1021/acs.jmedchem.6b01751 Mus musculus 8
28151659 10.1021/acs.jmedchem.6b01751 Cynomolgus monkey 8
38159286 10.1021/acs.jmedchem.3c02102 Mus musculus 6
29485864 10.1021/acs.jmedchem.7b01647 Receptor-interacting serine/threonine-protein kinase 1 4
28151659 10.1021/acs.jmedchem.6b01751 No relevant target 3
28151659 10.1021/acs.jmedchem.6b01751 Blood 3
36724216 10.1021/acs.jmedchem.2c02067 Mus musculus 3
35228069 10.1016/j.bmc.2022.116686 Receptor-interacting serine/threonine-protein kinase 1 3
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
31223438 10.1021/acsmedchemlett.9b00108 Receptor-interacting serine/threonine-protein kinase 1 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
33930803 10.1016/j.ejmech.2021.113484 HT-29 2
36288088 10.1021/acs.jmedchem.2c01478 HT-29 2
37364415 10.1016/j.bmc.2023.117385 HT-29 2
38484677 10.1016/j.ejmech.2024.116304 HT-29 2
37364415 10.1016/j.bmc.2023.117385 Mus musculus 2

Data from ChEMBL 36 via Core Engine