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