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Compound Detail

CHEMBL4098877

MLi-2
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C[C@@H]1CN(c2cc(-c3n[nH]c4ccc(OC5(C)CC5)cc34)ncn2)C[C@H](C)O1

Basic Information

ChEMBL ID CHEMBL4098877
Name MLi-2
Phase Preclinical
Structure Type MOL
InChI Key ATUUNJCZCOMUKD-OKILXGFUSA-N

Known Names

Merck lrrk2 inhibitor-2
15
Targets
81
Activities
3
Assay Types
30
PK Parameters
20
Publications
1
Known Names

Molecular Properties

379.5
MW (Da)
3.56
ALogP
6
HBA
1
HBD
76.2
PSA (Ų)
0.75
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C21H25N5O2
MW 379.46
Aromatic Rings 3
Heavy Atoms 28
NP-Likeness -0.81

Activity Summary

IC50 65 meas. best 9.4
Ki 9 meas. best 8.47
EC50 7 meas. best 8.91

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Leucine-rich repeat serine/threonine-protein kinase 2
CHEMBL1075104
IC50 9.4 8.95 0.4 25
Leucine-rich repeat serine/threonine-protein kinase 2
CHEMBL2010622
IC50 9.1 8.3913 0.8 8
Mus musculus
CHEMBL375
IC50 9.1 9.03 0.8 2
Leucine-rich repeat serine/threonine-protein kinase 2
CHEMBL1075104
EC50 8.91 8.0333 1.2 6
Leucine-rich repeat serine/threonine-protein kinase 2
CHEMBL1075104
Ki 8.47 8.47 3.4 1
Leucine-rich repeat serine/threonine-protein kinase 2
CHEMBL2010622
EC50 7.52 7.52 30.0 1
Dual specificity protein kinase CLK4
CHEMBL4203
IC50 6.65 6.65 225.0 3
Mitogen-activated protein kinase kinase kinase 14
CHEMBL5888
IC50 6.61 6.61 244.0 3
Mitogen-activated protein kinase kinase kinase 5
CHEMBL5285
IC50 6.37 6.37 428.0 3
Dual specificity protein kinase CLK2
CHEMBL4225
IC50 6.22 6.22 605.0 3
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 6.12 6.12 750.0 1
Dual specificity protein kinase TTK
CHEMBL3983
IC50 6.03 6.03 935.0 3
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 5.93 5.9233 1170.0 3
Peroxisome proliferator-activated receptor gamma
CHEMBL235
Ki 5.92 5.92 1190.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
Ki 5.57 5.57 2700.0 1
Unchecked
CHEMBL612545
Ki 5.48 5.48 3320.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
Ki 5.42 5.42 3790.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
IC50 5.42 5.42 3800.0 3
Sigma intracellular receptor 2
CHEMBL4105907
Ki 5.34 5.34 4570.9 3
Peroxisome proliferator-activated receptor gamma
CHEMBL235
IC50 5.19 5.19 6500.0 3
Muscarinic acetylcholine receptor M2
CHEMBL211
IC50 5.19 5.19 6400.0 3
Sodium/nucleoside cotransporter 2
CHEMBL5780
IC50 5.01 5.01 9700.0 1
Unchecked
CHEMBL612545
IC50 5.01 5.01 9700.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 493.3 ng.hr.mL-1 Rattus norvegicus
AUC 250.44 ng.hr.mL-1 Rattus norvegicus
AUC 251.96 ng.hr.mL-1 Mus musculus
AUC 569.19 ng.hr.mL-1 Mus musculus
CL 153.0 mL.min-1.kg-1 Rattus norvegicus
CL 153.0 mL.min-1.kg-1 Rattus norvegicus
CL 12700.0 mL.min-1.kg-1 Rattus norvegicus
CL 37.0 mL.min-1.kg-1 Canis lupus familiaris
CL 3200.0 mL.min-1.kg-1 Canis lupus familiaris
CL 16.0 mL.min-1.kg-1 Macaca mulatta
CL 3400.0 mL.min-1.kg-1 Macaca mulatta
Cmax 716.0 nM Mus musculus
Cmax 298.0 nM Mus musculus
F 39.0 % Rattus norvegicus
F 38.0 % Rattus norvegicus
F 100.0 % Canis lupus familiaris
F 45.0 % Mus musculus
Fu 0.012 - Rattus norvegicus
Fu 0.008 - Mus musculus
Fu 0.009 - Mus musculus
MRT 4.0 hr Rattus norvegicus
MRT 1.7 hr Rattus norvegicus
MRT 2.0 hr Rattus norvegicus
MRT 7.0 hr Canis lupus familiaris
MRT 1.5 hr Macaca mulatta
MRT 2.7 hr Mus musculus
MRT 11.0 hr Mus musculus
T1/2 1.8 hr Rattus norvegicus
Tmax 1.3 hr Rattus norvegicus
Tmax 0.75 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.4 nM 9.4 Inhibition of full-length LRRK2 G2019S mutant (unknown origin) using LRRKtide as... 35707141
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.4 nM 9.4 Inhibition of full length LRRK2 G2019S mutant (unknown origin) by LRRKtide Adapt... 34992038
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.4 nM 9.4 Inhibition of LRRK2 G2019S mutant (unknown origin) 36049274
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.4 nM 9.4 Inhibition of LRRK2 G2019S mutant (unknown origin) using LRRKtide as substrate p... 37734423
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.5 nM 9.3 Inhibition of LRRK2 (unknown origin) 34864194
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.5 nM 9.3 Inhibition of GST20-tagged human LRRK2 G2019S mutant using LRRKtide peptide prei... 36475697
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.76 nM 9.12 Inhibition of GST-tagged truncated human LRRK2 G2019S mutant in presence of ATP 37201428
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.76 nM 9.12 Affinity Biochemical interaction (LanthaScreen) EUB0000715a LRRK2 -
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.76 nM 9.12 Inhibition of GST tagged human LRRK2 G2019S mutant using LRRKtide as substrate i... 26407721
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.76 nM 9.12 Inhibition of recombinant human GST-tagged LRRK2 (970 to 2527 residues) G2019S m... 28245354
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.8 nM 9.1 In vivo inhibition of LRRK2 in C57Bl/6 mouse brain assessed as reduction in pSer... 26407721
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.8 nM 9.1 Inhibition of recombinant human GST-tagged LRRK2 G2019S mutant catalytic domain ... 32352776
Mus musculus IC50 = 0.8 nM 9.1 In vivo inhibition of LRRK2 Ser935 phosphorylation in mouse brain assessed as un... 28245354
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.9 nM 9.05 Inhibition of phosphorylated human LRRK2 G2019S mutant at S93 in human HEK293 ce... 37734423
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 0.9 nM 9.05 Inhibition of human LRRK2 G2019S mutant phosphorylation at S1292 in human HEK293... 37734423
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 1.0 nM 9.0 Inhibition of full-length wild type LRRK2 (unknown origin) using LRRKtide as sub... 35707141
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 1.0 nM 9.0 Km ATP LanthaScreen Assay: a) 400 nl of a 1:2.15 serial dilution of test compoun... -
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 1.0 nM 9.0 Inhibition of full length wild type LRRK2 (unknown origin) by LRRKtide Adapta as... 34992038
Leucine-rich repeat serine/threonine-protein kinase 2 IC50 = 1.0 nM 9.0 Inhibition of wildtype full length LRRK2 (unknown origin) 36049274
Mus musculus IC50 = 1.1 nM 8.96 In vivo inhibition of LRRK2 Ser935 phosphorylation in mouse brain assessed as un... 28245354

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4507291 Unchecked 31
26407721 10.1124/jpet.115.227587 Leucine-rich repeat serine/threonine-protein kinase 2 29
26407721 10.1124/jpet.115.227587 ADMET 23
- 10.6019/CHEMBL4507291 Tyrosine-protein kinase ABL1 20
26407721 10.1124/jpet.115.227587 Mus musculus 20
- 10.6019/CHEMBL4507291 Epidermal growth factor receptor 18
36475697 10.1021/acs.jmedchem.2c01605 ADMET 15
28245354 10.1021/acs.jmedchem.7b00045 Rattus norvegicus 14
- 10.6019/CHEMBL4507291 Receptor-type tyrosine-protein kinase FLT3 13
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL4507291 Mast/stem cell growth factor receptor Kit 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL4507291 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 10
- 10.6019/CHEMBL4689842 HEK-293T 9
- 10.6019/CHEMBL4689842 Fibroblast 9
- 10.6019/CHEMBL5724696 U2OS 8
- 10.6019/CHEMBL4507291 Leucine-rich repeat serine/threonine-protein kinase 2 8
34992038 10.1016/j.ejmech.2021.114080 Leucine-rich repeat serine/threonine-protein kinase 2 8
- 10.6019/CHEMBL4507291 Proto-oncogene tyrosine-protein kinase receptor Ret 7
- 10.6019/CHEMBL4507291 Sodium-dependent noradrenaline transporter 7

Data from ChEMBL 36 via Core Engine