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ChemicalBook--->CAS DataBase List--->1456858-57-3

1456858-57-3

1456858-57-3 Structure

1456858-57-3 Structure
IdentificationBack Directory
[Name]

MRT 199665
[CAS]

1456858-57-3
[Synonyms]

MRT 199665
MRT199665,MRT-199665
6H-Pyrrolo[2,3-d]pyrimidin-6-one, 7-[(1S)-2,3-dihydro-4-hydroxy-1H-inden-1-yl]-5,7-dihydro-5,5-dimethyl-2-[[3-(1-pyrrolidinylmethyl)phenyl]amino]-
[Molecular Formula]

C28H31N5O2
[MDL Number]

MFCD32878230
[MOL File]

1456858-57-3.mol
[Molecular Weight]

469.58
Chemical PropertiesBack Directory
[Boiling point ]

707.6±70.0 °C(Predicted)
[density ]

1.318±0.06 g/cm3(Predicted)
[form ]

Solid
[pka]

10.14±0.40(Predicted)
[color ]

Off-white to light yellow
Hazard InformationBack Directory
[Uses]

MRT199665 is a potent and ATP-competitive, selective MARK/SIK/AMPK inhibitor with IC50s of 2/2/3/2 nM, 10/10 nM, and 110/12/43 nM for MARK1/MARK2/MARK3/MARK14, AMPKα1/AMPKα2, and SIK1/SIK2/SIK3, respectively[1]. MRT199665 causes apoptosis in MEF2C-activated human acute myeloid leukemias (AML) cells[2]. MRT199665 inhibits the phosphorylation of SIK substrate CRTC3 at S370[3].
[IC 50]

MARK1: 2 nM (IC50); MARK2: 2 nM (IC50); MARK3: 3 nM (IC50); MARK4: 2 nM (IC50); SIK1: 110 nM (IC50); SIK2: 12 nM (IC50); SIK3: 43 nM (IC50); NUAK1: 3 nM (IC50); NUAK2: 120 nM (IC50); AMPKα1: 10 nM (IC50); AMPKα2: 10 nM (IC50); MELK: 29 nM (IC50); TBK1: 5400 nM (IC50); IKKε: 7700 nM (IC50); BRSK2: 10000 nM (IC50)
[References]

[1] Clark K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91. DOI:10.1073/pnas.1215450109
[2] Brown FC, et al. MEF2C Phosphorylation Is Required for Chemotherapy Resistance in Acute Myeloid Leukemia. Cancer Discov. 2018 Apr;8(4):478-497. DOI:10.1158/2159-8290.CD-17-1271
[3] Hutchinson LD, et al. Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses.Cell Death Dis. 2020 Jan 22;11(1):49. DOI:10.1038/s41419-020-2241-6
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