Chemical Probes logo
M4K2234 | M4K2234 : Inhibitor of ACVRL1, ACVR1
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
Download

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
ACVRL1
  • IC50:7 nM
  • IC50:83 nM
  • INH:100 nM
ACVR1
  • IC50:14 nM
  • IC50:13 nM
  • INH:100 nM
Inhibitor
Use 100–500 nM as the highest concentration to prioritize targeting ALK1, TNIK, and ALK2.
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
TNIK

Gene ID: Q9UKE5

Organism: Homo sapiens

Family: STE Ser/Thr protein kinase family

Potency: IC50 - 41 nM

Selectivity Assessment Description:
The selectivity profile of M4K2234 was determined by kinome-wide screening against 375 protein kinas ...
In Cell Selectivity Assessment
Selectivity Assessment Description:
M4K2234 exhibited only very weak potency against ALK4/5.

Potency
Cellular
In Vitro

ACVRL1

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.0c00395

ACVR1

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.0c00395

In Vivo Validations

Mouse
Dose: 10 mg/Kg
Route of delivery: Oral
Plasma half life: 1.3 h
Systemic clearance: 31 ml/min/Kg
Cmax: 3000 nM
Bioavailability: 71%
Volume of Distribution at Steady-State: 3 L/Kg

DOI Reference: 10.1021/acs.jmedchem.0c00395

Negative Control Compounds

M4K2234-NC
SMILES: O=C(C1=C(C=C(C=C1F)C2=C(C(C3=CC=C(C=C3)N4CCN(CC4)C(C)C)=CN=C2)C)OC)N5CCCC5

Chemical Information

Molecular Formula C27H31FN4O2
SMILEs COc1cc(-c2cncc(-c3ccc(N4CCN(C(C)C)CC4)cc3)c2C)cc(F)c1C(N)=O
InChI InChI=1S/C27H31FN4O2/c1-17(2)31-9-11-32(12-10-31)21-7-5-19(6-8-21)22-15-30-16-23(18(22)3)20-13-24(28)26(27(29)33)25(14-20)34-4/h5-8,13-17H,9-12H2,1-4H3,(H2,29,33)
Molecular weight 462.24 Da
AlogP 4.501020000000003
HBond acceptors 6
HBond donors 2
Atoms 65

Vendors

Note: This is not an exhaustive list and does not indicate endorsement by the portal.

Expert Reviews

by SERP
(on 26 Jun 2022 )
Cellular Use Rating
In Model Organisms
M4K2234 is a reasonable cellular probe to interrogate ALK1/2 biology in cells. The data reported for this compound in the JMC 2020 publication confirms good on-target dual selectivity, however, there...
by SERP
(on 30 Jun 2022 )
Cellular Use Rating
In Model Organisms
Cellular off-target data against ALK3, ALK6 and TNIK is a desirable addition to the data package, since these kinases have in vitro IC50s in the double digit nM range. The cut-off range for off-target...
by SERP
(on 6 Jul 2022 )
Cellular Use Rating
In Model Organisms
M4K2234 is a relatively selective ALK1, TINK, and ALK2 inhibitor. The compound's utility is improved when paired with M4K2234NC, a non-active control compound. M4K2234 can be used to selectively modulate...
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria