Chemical Probes logo
URMC-099 | Inhibitor of MAP3K9, MAP3K10, MAP3K11
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
MAP3K9
  • IC 50:19 nM
  • IC50:0.51 uM
MAP3K10
  • IC 50:42 nM
  • IC 50:0.51 uM
MAP3K11
  • IC 50:14 nM
  • IC 50:0.51 uM
Inhibitor
--

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - LRRK2 11 nM, DLK 150 nM, ABL T315I 3 nM, FLT3 4 nM

Potency Assay Off-Target:
In ScanMax Assay (DiscoveRx), URMC-099 inhibited 111 of 442 kinases >90% at 1 uM. In radiometric as ...
Selectivity Assessment Description:
In ScanMax Assay (DiscoveRx), URMC-099 inhibited 111 of 442 kinases >90% at 1 uM. In radiometric ass ...
In Cell Selectivity Assessment
Selectivity Assessment Description:
Negligible activity against hERG in automated CEREP whole-cell patch clamp assays, IC50 = 21 uM.

Potency
Cellular
In Vitro

MAP3K9

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/jm401094t

MAP3K10

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/jm401094t

MAP3K11

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/jm401094t

In Vivo Validations

Mouse
Dose: 10 mg/kg
Route of delivery: Intravenous
Plasma half life: 2.72 hr
Systemic clearance: 2.9 L/h/kg
Organ of interest (O): Brain
Target engagement assay: Indirect: inhibition of substrate phosphorylation in the brain

DOI Reference: 10.1021/jm401094t

Chemical Information

Molecular Formula C27H27N5
SMILEs CN1CCN(Cc2ccc(-c3cnc4[nH]cc(-c5ccc6[nH]ccc6c5)c4c3)cc2)CC1
InChI InChI=1S/C27H27N5/c1-31-10-12-32(13-11-31)18-19-2-4-20(5-3-19)23-15-24-25(17-30-27(24)29-16-23)21-6-7-26-22(14-21)8-9-28-26/h2-9,14-17,28H,10-13,18H2,1H3,(H,29,30)
Molecular weight 421.23 Da
AlogP 0.0
HBond acceptors 5
HBond donors 2
Atoms 59
PAINS * Yes

* This is an automated alert only, and may not necessarily indicate an issue with this probe. ( Learn more about PAINS )

References

Publications

Cross References

canSARChEMBLBindingDB

Vendors

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

Expert Reviews

by SERP
(on 20 Jun 2016 )
Cellular Use Rating
In Model Organisms
This is a promiscuous kinase inhibitor with significant off-target activity.
by SERP
(on 24 Jun 2016 )
Cellular Use Rating
In Model Organisms
This compound is an orally bioavailable, brain-penetrant inhibitor of MLK, but it show poor selectivity against many other protein kinases.
by SERP
(on 1 Jul 2016 )
Cellular Use Rating
In Model Organisms
This compound is rather promiscuous and targets several kinases other than the MLK family with equal or even greater potency.

Portal Comments

In a 2023 study, Hu et al. evaluated URMC-099 in live-cell assays for Phospholipidosis induction, cautioning about adverse effects at concentrations near 1 uM. (DOI:10.1016/j.chembiol.2023.09.003)

(last updated: 7 Nov 2023)

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