Identification | Back 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 Properties | Back 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 Information | Back 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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