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Assay Detail

CHEMBL5732230

Review assay metadata, readout intent, target linkage, and publication context from the same page.

Binding
ROCK1 and ROCK2 Compound Selectivity: Dose response curves for Rho-kinase inhibition were derived from a Millipore immuno-based 96 well plate assay (Millipore catalog number CSA001). Purified active ROCK1 and ROCK2 were obtained from Invitrogen (catalog numbers ROCK1, PV3691 and ROCK2, PV3759). The kit components include assay plates, which are pre-coated with recombinant MYPT1, which contains a specifically phosphorylatable Thr696. The inhibitory activities of compounds are measured according to the manufactures protocol. Briefly, decreasing concentrations of test compounds or the known ROCK inhibitor Y-27963, are added, from 50 uM to 0.003 uM to reaction buffer containing 5 mM MgCl2, and 10 mUnits of ROCK1 or ROCK2 in assay dilution buffer. This mixture is overlayed into the 96 well plate and the reaction is initiated with the addition of 2.5 uM ATP. The assay proceeds at 30° Celsius for 30 minutes with gentle shaking at 120 rpm. The assay is terminated by washing of the plate 3 times with Tris-buffered saline and tween wash buffer. Anti-phospho-MYPT1 (Thr696) antibody is added to each well to detect the phosphorylated substrate and incubated for 1 hour at room temperature after which HRP conjugated anti-rabbit IgG secondary is added for 1 hour at room temperature. After washing the assay is developed using a substrate reagent and the absorbance is read at 450 nm on a Tecan Infinite M1000 reflecting the relative remaining ROCK phosphorylation activity.
141
Total Activities
36
Compounds Tested
4
Activity Types
0
Assay Parameters

Assay Information

Assay Type Binding
Organism Homo sapiens
Confidence 9 — Direct single protein target
Curated By Autocuration

Target

Rho-associated protein kinase 2 (CHEMBL2973)
Type SINGLE PROTEIN
Organism Homo sapiens

Publication

Rho kinase inhibitors
(2019)

Activity Statistics

Type Count Avg pChEMBL Best pChEMBL
kon 47 - -
k_off 47 - -
IC50 39 6.65 7.89
Ki 8 7.27 7.70

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL5992096 3 7.89
CHEMBL5858473 6 7.70
CHEMBL5819970 3 7.70
CHEMBL5768727 9 7.70
CHEMBL5749663 3 7.52
CHEMBL5815614 3 7.52
CHEMBL5936293 3 7.52
CHEMBL5850835 9 7.52
CHEMBL5898334 3 7.40
CHEMBL2005186 BELUMOSUDIL 4.0 6 7.40
CHEMBL5882290 3 7.40
CHEMBL5763746 3 7.30
CHEMBL6021969 3 7.22
CHEMBL559147 Y-27632 6 7.22
CHEMBL5896038 3 7.22
CHEMBL5751696 3 7.16
CHEMBL5790296 3 7.16
CHEMBL6016872 9 7.16
CHEMBL5819432 3 7.10
CHEMBL5744109 3 7.10
CHEMBL5828705 3 6.92
CHEMBL5986438 6 6.77
CHEMBL5841511 6 6.75
CHEMBL5817799 3 6.72
CHEMBL5794019 3 6.70
CHEMBL6003524 3 6.51
CHEMBL5989311 3 6.47
CHEMBL5898268 3 6.42
CHEMBL5958076 3 6.40
CHEMBL5953458 3 6.30

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL5992096 IC50 = 13.0 nM 7.89
CHEMBL5858473 Ki = 20.0 nM 7.70
CHEMBL5768727 Ki = 20.0 nM 7.70
CHEMBL5819970 IC50 = 20.0 nM 7.70
CHEMBL5936293 IC50 = 30.0 nM 7.52
CHEMBL5850835 Ki = 30.0 nM 7.52
CHEMBL5815614 IC50 = 30.0 nM 7.52
CHEMBL5749663 IC50 = 30.0 nM 7.52
CHEMBL5850835 IC50 = 30.0 nM 7.52
CHEMBL2005186 BELUMOSUDIL Ki = 40.0 nM 7.40
CHEMBL5898334 IC50 = 40.0 nM 7.40
CHEMBL5882290 IC50 = 40.0 nM 7.40
CHEMBL5763746 IC50 = 50.0 nM 7.30
CHEMBL6021969 IC50 = 60.0 nM 7.22
CHEMBL559147 Y-27632 Ki = 60.0 nM 7.22
CHEMBL5896038 IC50 = 60.0 nM 7.22
CHEMBL5790296 IC50 = 70.0 nM 7.16
CHEMBL6016872 IC50 = 70.0 nM 7.16
CHEMBL5751696 IC50 = 70.0 nM 7.16
CHEMBL5819432 IC50 = 80.0 nM 7.10
CHEMBL6016872 Ki = 80.0 nM 7.10
CHEMBL5744109 IC50 = 80.0 nM 7.10
CHEMBL5828705 IC50 = 120.0 nM 6.92
CHEMBL5986438 Ki = 170.0 nM 6.77
CHEMBL5841511 Ki = 180.0 nM 6.75
CHEMBL5817799 IC50 = 191.0 nM 6.72
CHEMBL5794019 IC50 = 200.0 nM 6.70
CHEMBL6003524 IC50 = 310.0 nM 6.51
CHEMBL5989311 IC50 = 340.0 nM 6.47
CHEMBL5898268 IC50 = 380.0 nM 6.42
CHEMBL5958076 IC50 = 400.0 nM 6.40
CHEMBL5768727 IC50 = 470.0 nM 6.33
CHEMBL5953458 IC50 = 500.0 nM 6.30
CHEMBL5858473 IC50 = 540.0 nM 6.27
CHEMBL6056601 IC50 = 700.0 nM 6.16
CHEMBL5850835 IC50 = 720.0 nM 6.14
CHEMBL5899291 IC50 = 1000.0 nM 6.00
CHEMBL5768727 IC50 = 1000.0 nM 6.00
CHEMBL2005186 BELUMOSUDIL IC50 = 1020.0 nM 5.99
CHEMBL559147 Y-27632 IC50 = 1630.0 nM 5.79
CHEMBL6016872 IC50 = 1960.0 nM 5.71
CHEMBL5991297 IC50 = 3200.0 nM 5.50
CHEMBL5986438 IC50 = 4250.0 nM 5.37
CHEMBL5841511 IC50 = 4640.0 nM 5.33
CHEMBL5967940 IC50 = 4900.0 nM 5.31
CHEMBL5794019 k_off = - s-1 -
CHEMBL5815614 kon = - -
CHEMBL5828705 k_off = - s-1 -
CHEMBL5898268 kon = - -
CHEMBL5828705 kon = - -