ULK-101

Protein target name:

ULK1, ULK2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 5 uM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

Autophagy Activating Kinases

HUGO ID:

HGNC:12558 HGNC:13480

Entrez gene ID:

8408 9706

UNIPROT ID:

O75385 Q8IYT8

Target alias:

ATG1; ATG1A; UNC51; hATG1; Unc51.1; ATG1B, Unc51.2

Probe Details

Chemical Probes Portal ID:

CPP1848

Probe alias:

ULK101

PubChem CID:

137628686

SMILES string:

FC1=CC=C(C(C=N2)=CN3C2=C(C4=CSC(C(N[C@@H](C5CC5)C(F)(F)F)=O)=C4)C=N3)C=C1

InChi Key:

PFZRXJIYAFANHP-IBGZPJMESA-N

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

8.3 (ULK1), 30 (ULK2) nM

Potency assay:

Kinase profiler (Eurofin)

Off target activity

Potency (off target):

IC50

Off target protein and potency:

DRAK1 14 nMMNK2 22 mM

Potency assay (off target):

Radiometric Assay

Probe Selectivity in Vitro:

Tested in vitro in a radiometric assay against 327 recombinant kinases. DRAK1 to be 14 nM and that of MNK2 to be 22 nM.

In cell validation

On target activity in cells

Potency in cells:

EC50

390 nM

Potency assay (cells):

Quantification OF pSer15-BECLIN 1

Target engagement assay (cells):

Tested at conc. between 0-5 uM, reduces BafA1 induced LC3B-II accumulation in U2OS cells in a concentration-dependent manner

Primary Reference

Reference (doi):

10.1016/j.isci.2018.09.012

Reference (PMID):

30292171

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

2 review(s)

Rating for use in Model Organisms

no rating

SAB Members

SAB Comments

ULK-101 looks to be an appropriate tool for in vitro/in cellulo studies. Kinase selectivity data is included within the supplementary data. Further confidence in use as probe would come from availability of wider selectivity data (i.e. targets other than kinases) and ideally a negative chemical probe. The molecule may be suitable for in vivo use but no data are available. Additionally these data at present come from a single publication.

Jul 11 2020 - 3:31pm

ULK-101 is a potentially valuable probe for studying ULK1 biology in cells, as it is potent against ULK-1 (8.3 nM) and quite selective against the kinome, with only 2 off-target kinases inhibited at similar potency levels (it was determined that the IC50 for DRAK1 is 14 nM and that of MNK2 to be 22 nM). Moreover, ULK-101 inhibits ULK2 at 30 nM, suggesting that at least at doses above 1 uM in cell tissue studies it has good coverage for this possibly redundant target as well. These features suggest that ULK-101 is a “best in class” probe against ULK1. It is slightly less potent than the structurally related analog ULK-100, but it is significantly more selective. There is no data disclosed against targets outside the kinase class, but the scaffold appears to have no features suggesting it should potently modify other protein classes (e.g ion channels, GPCRs). There is no disclosed in vivo efficacy or pharmacokinetic data, so use in the context of in vivo experiments should proceed with care until pharmacokinetic data or pharmacodynamic data is determined.

Aug 28 2020 - 7:55am

ULK-101

Probe Availability

Probe Information

Target Details

ATG1; ATG1A; UNC51; hATG1; Unc51.1; ATG1B, Unc51.2

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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ULK-101

Probe Availability

Probe Information

Target Details

ATG1; ATG1A; UNC51; hATG1; Unc51.1; ATG1B, Unc51.2

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?