MRT67307 HCl

• CAT Number: I008197
• CAS Number: 2080306-21-2
• Molecular Formula: C27H38Cl2N4O
• Molecular Weight: 505.528
• Purity: ≥95%
• Target: SIK inhibitor
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• Related CAS: 1190379-70-4 (HCl)
• InChI: InChI=1S/C27H36N4O.2ClH/c1-31-15-12-21-16-23(9-8-22(21)18-31)30-24-10-11-25(19-6-7-19)26(17-24)28-13-3-14-29-27(32)20-4-2-5-20;;/h8-11,16-17,19-20,28,30H,2-7,12-15,18H2,1H3,(H,29,32);2*1H
• InChIKey: AVTUJIVDDXSHKB-UHFFFAOYSA-N
• SMILES: O=C(C1CCC1)NCCCNC2=CC(NC3=CC4=C(CN(C)CC4)C=C3)=CC=C2C5CC5.[H]Cl.[H]Cl

MRT67307 HCl(CAT: I008197) is a potent ULK inhibitor and SIK inhibitor. MRT67307 potently inhibits ULK1 and ULK2 in vitro and blocks autophagy in cells. ULK1 inhibition results in the accumulation of stalled early autophagosomal structures, indicating a role for ULK1 in the maturation of autophagosomes as well as initiation.

Reference

1. J Biol Chem. 2015 May 1;290(18):11376-83. doi: 10.1074/jbc.C114.627778. Epub 2015
Apr 1.

Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin
(mTOR)-dependent autophagy.

Petherick KJ(1), Conway OJ(1), Mpamhanga C(2), Osborne SA(2), Kamal A(2), Saxty
B(2), Ganley IG(3).

Author information:
(1)From the Medical Research Council (MRC) Protein Phosphorylation and
Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1
5EH, Scotland and.
(2)the MRC Technology Centre for Therapeutics Discovery, 1-3 Burtonhole Lane,
Mill Hill, London NW7 1AD, United Kingdom.
(3)From the Medical Research Council (MRC) Protein Phosphorylation and
Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1
5EH, Scotland and .

Erratum in
J Biol Chem. 2015 Nov 27;290(48):28726.

Autophagy is a cell-protective and degradative process that recycles damaged and
long-lived cellular components. Cancer cells are thought to take advantage of
autophagy to help them to cope with the stress of tumorigenesis; thus targeting
autophagy is an attractive therapeutic approach. However, there are currently no
specific inhibitors of autophagy. ULK1, a serine/threonine protein kinase, is
essential for the initial stages of autophagy, and here we report that two
compounds, MRT67307 and MRT68921, potently inhibit ULK1 and ULK2 in vitro and
block autophagy in cells. Using a drug-resistant ULK1 mutant, we show that the
autophagy-inhibiting capacity of the compounds is specifically through ULK1. ULK1
inhibition results in accumulation of stalled early autophagosomal structures,
indicating a role for ULK1 in the maturation of autophagosomes as well as
initiation.