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Compound Detail

CHEMBL1952329

SGI-1776
Phase I
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Phase I
CN1CCC(CNc2ccc3ncc(-c4cccc(OC(F)(F)F)c4)n3n2)CC1

Basic Information

ChEMBL ID CHEMBL1952329
Name SGI-1776
Phase Phase I
Structure Type MOL
InChI Key MHXGEROHKGDZGO-UHFFFAOYSA-N

Known Names

Sgi-1776
27
Targets
74
Activities
4
Assay Types
0
PK Parameters
20
Publications
1
Known Names
3
Indications
1
Mechanisms

Molecular Properties

405.4
MW (Da)
4.05
ALogP
6
HBA
1
HBD
54.7
PSA (Ų)
0.69
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Extended Properties

Molecular Formula C20H22F3N5O
MW 405.42
Aromatic Rings 3
Heavy Atoms 29
NP-Likeness -1.61

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine/threonine-protein kinase PIM inhibitor INHIBITOR Serine/threonine-protein kinase PIM

Indications

Leukemia Lymphoma, Non-Hodgkin Prostatic Neoplasms, Castration-Resistant

Activity Summary

IC50 50 meas. best 8.15
Kd 15 meas. best 7.64
Ki 7 meas. best 7.92
EC50 2 meas. best 6.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase pim-1
CHEMBL2147
IC50 8.15 7.9717 7.0 18
Serine/threonine-protein kinase pim-1
CHEMBL2147
Ki 7.92 7.84 12.0 3
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 7.68 7.44 21.0 4
5'-AMP-activated protein kinase subunit gamma-2
CHEMBL2453
Kd 7.64 7.64 23.0 1
Serine/threonine-protein kinase pim-3
CHEMBL5407
Ki 7.62 7.62 24.0 2
Interleukin-1 receptor-associated kinase 3
CHEMBL5081
Kd 7.58 7.58 26.0 1
MV4-11
CHEMBL613835
IC50 7.52 7.52 30.0 1
Serine/threonine-protein kinase haspin
CHEMBL1075163
IC50 7.47 7.47 34.0 1
Serine/threonine-protein kinase pim-2
CHEMBL4523
IC50 7.44 6.5363 36.3 8
Serine/threonine-protein kinase pim-1
CHEMBL2147
Kd 7.37 7.37 43.0 1
Serine/threonine-protein kinase pim-3
CHEMBL5407
IC50 7.3 7.18 50.5 7
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
Kd 6.84 6.84 143.0 1
Serine/threonine-protein kinase pim-1
CHEMBL2147
EC50 6.7 6.7 200.0 1
Tyrosine-protein kinase Yes
CHEMBL2073
IC50 6.62 6.095 240.0 2
Activin receptor type-1
CHEMBL5903
Kd 6.34 6.34 458.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 6.29 6.1 511.0 3
Unchecked
CHEMBL612545
IC50 6.22 6.22 600.0 1
Serine/threonine-protein kinase pim-2
CHEMBL4523
Ki 6.21 6.21 610.0 2
Platelet-derived growth factor receptor beta
CHEMBL1913
Kd 5.79 5.79 1607.0 1
WI-38
CHEMBL614391
IC50 5.77 5.77 1700.0 1
Serine/threonine-protein kinase 10
CHEMBL3981
Kd 5.67 5.67 2159.0 1
K562
CHEMBL385
IC50 5.64 5.64 2290.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
Kd 5.49 5.49 3217.0 1
STE20-like serine/threonine-protein kinase
CHEMBL4202
Kd 5.45 5.45 3588.0 1
PC-3
CHEMBL390
IC50 5.32 5.32 4830.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 5.31 5.31 4860.0 1
NON-PROTEIN TARGET
CHEMBL3879801
EC50 5.3 5.3 5000.0 1
Serine/threonine-protein kinase SIK2
CHEMBL5699
Kd 5.21 5.21 6124.0 1
LNCaP
CHEMBL612518
IC50 5.16 5.16 6850.0 1
Casein kinase II subunit alpha'
CHEMBL4070
Kd 5.1 5.1 7924.0 1
BMP-2-inducible protein kinase
CHEMBL4522
Kd 5.07 5.07 8535.0 1
Cyclin-G-associated kinase
CHEMBL4355
Kd 5.06 5.06 8634.0 1
Ribosomal protein S6 kinase alpha-6
CHEMBL4924
Kd 4.62 4.62 23762.0 1
Serine/threonine-protein kinase N1
CHEMBL3384
Kd 4.45 4.45 35424.0 1

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of PIM1 (unknown origin) 38164076
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of PIM1 22266039
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Competitive inhibition of PIM1 in presence of ATP 22924342
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of human Pim1 after 40 mins using [gamma33P]ATP by scintillation coun... 26804231
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of recombinant human full length N-terminal GST-tagged PIM1 expressed... 28341403
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of human recombinant PIM1 in presence of ATP by ELISA based spectroph... 28760531
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of PIM1 (unknown origin) 29871845
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of PIM1 (unknown origin) 30530193
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of human recombinant PIM1 using KKRNRTLTV as substrate in presence of... 30802730
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of N-terminal GST-tagged recombinant human full length Pim-1 using KK... 31207462
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of recombinant human full length N-terminal GST-tagged PIM1 expressed... 33128909
Serine/threonine-protein kinase pim-1 IC50 = 7.0 nM 8.15 Inhibition of PIM1 (unknown origin) 34607244
Serine/threonine-protein kinase pim-1 IC50 = 7.6 nM 8.12 Inhibition of Pim1 (unknown origin) using luciferase-luciferin based ATP detecti... 25589932
Serine/threonine-protein kinase pim-1 Ki = 12.0 nM 7.92 Inhibition of PIM1 (unknown origin) up to 120 mins by Michaelis-Menten plot anal... 30954777
Serine/threonine-protein kinase pim-1 IC50 = 13.0 nM 7.89 Inhibition of His tagged human recombinant PIM1 using PIM tide (ARKRRRHPSGPPTA) ... 30802730
Serine/threonine-protein kinase pim-1 Ki = 16.0 nM 7.8 Inhibition of PIM1 (unknown origin) 24900629
Serine/threonine-protein kinase pim-1 Ki = 16.0 nM 7.8 Inhibition of PIM1 kinase (unknown origin) using Biotin-AGAGRSRHSSYPAGT-OH as su... 26505898
Serine/threonine-protein kinase pim-1 IC50 = 20.0 nM 7.7 Inhibition of PIM1 (unknown origin) 28001064
Receptor-type tyrosine-protein kinase FLT3 IC50 = 21.0 nM 7.68 Inhibition of human FLT3 using EAIYAAPFAKKK as substrate incubated for 60 mins b... 30802730
5'-AMP-activated protein kinase subunit gamma-2 Kd = 23.0 nM 7.64 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878

Literature References

PubMed DOI Target Context # Activities
34515481 10.1021/acs.jmedchem.1c01084 MOLM-13 13
29871845 10.1016/j.bmcl.2018.05.054 HepG2 8
34515481 10.1021/acs.jmedchem.1c01084 Unchecked 6
29191878 10.1126/science.aan4368 Unchecked 5
26804231 10.1016/j.bmcl.2016.01.032 Serine/threonine-protein kinase pim-1 5
33691794 10.1186/s13148-021-01037-1 A549 4
30802730 10.1016/j.ejmech.2019.02.022 Serine/threonine-protein kinase pim-1 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
23787099 10.1016/j.bmcl.2013.05.072 Tyrosine-protein kinase Yes 2
33128909 10.1016/j.bmc.2020.115724 Serine/threonine-protein kinase pim-1 2
34515481 10.1021/acs.jmedchem.1c01084 Serine/threonine-protein kinase PIM 2
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 2
30802730 10.1016/j.ejmech.2019.02.022 Serine/threonine-protein kinase pim-3 2
30802730 10.1016/j.ejmech.2019.02.022 Serine/threonine-protein kinase pim-2 2
28341403 10.1016/j.bmc.2017.02.056 Unchecked 2
33128909 10.1016/j.bmc.2020.115724 Unchecked 2
30802730 10.1016/j.ejmech.2019.02.022 Receptor-type tyrosine-protein kinase FLT3 2
- 10.6019/CHEMBL3301361 ADMET 1
25589932 10.1021/ml500300c Voltage-gated inwardly rectifying potassium channel KCNH2 1

Data from ChEMBL 36 via Core Engine