| Identification | Back Directory | [Name]
DS-437 | [CAS]
1674364-87-4 | [Synonyms]
DS-437
DS-437
(DS437
DS-437 >=98% (HPLC)
Adenosine, 5'-S-[2-[[(ethylamino)carbonyl]amino]ethyl]-5'-thio- | [Molecular Formula]
C15H23N7O4S | [MDL Number]
MFCD32661891 | [MOL File]
1674364-87-4.mol | [Molecular Weight]
397.45 |
| Chemical Properties | Back Directory | [density ]
1.71±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO:125.0(Max Conc. mg/mL);314.5(Max Conc. mM) | [form ]
powder | [pka]
13.13±0.70(Predicted) | [color ]
white to beige | [InChIKey]
CACMCLIHCDTJHL-XNZUMOJTSA-N | [SMILES]
NC1=NC=NC2=C1N=CN2[C@H]3[C@H](O)[C@H](O)[C@@H](CSCCNC(NCC)=O)O3 |
| Safety Data | Back Directory | [Symbol(GHS) ]
GHS06 | [Signal word ]
Danger | [Hazard statements ]
H301 | [Precautionary statements ]
P301+P330+P331+P310 | [RIDADR ]
UN 2811 6.1 / PGIII | [WGK Germany ]
WGK 3 | [Storage Class]
6.1C - Combustible acute toxic Cat.3
toxic compounds or compounds which causing chronic effects | [Hazard Classifications]
Acute Tox. 3 Oral |
| Hazard Information | Back Directory | [Description]
DS-437 is a dual inhibitor of protein arginine methyltransferase 5 (PRMT5) and PRMT7 (IC50s = 5.9 and 6 μM, respectively). It is selective for PRMT5 and PRMT7 over a panel of 29 additional protein, DNA, and RNA methyltransferases at 50 μM, but also inhibits DNMT3A and DNMT3B (IC50s = 52 and 62 μM, respectively). DS-437 (2.5 and 10 μM) inhibits symmetrical arginine dimethylation of FOXP3 in HEK293T cells, as well as symmetrical arginine dimethylation of p60 and the ribonucleoproteins SmD1/D3 and SmB/B’ in MDA-MB-231 cells in a concentration-dependent manner. It inhibits the ability of regulatory T cells (Tregs) to suppress effector T cell (Teff) proliferation in vitro in human and murine Treg suppression assays. DS-437 (10 mg/kg five times per week) reduces tumor growth in a CT26Her2 murine colon cancer model when administered in combination with the anti-p185erbB2/neu antibody 4D5. | [Uses]
DS-437 has been used as an inhibitor of protein arginine methyltransferase 5 (PRMT5) to study its effect on forkhead box P3 (FOXP3) methylation and regulatory T cells (Tregs) function in 293T cells. | [Biochem/physiol Actions]
DS-437 is an analog of S-adenosyl methionine (SAM ), which inhibits protein arginine methyltransferases PRMT5 and PRMT7 (IC50 5.9 and 6 μM) with little interaction against a panel of 30 other human methyltransferases. | [in vivo]
DS-437 (10 mg/kg; i.p.; 5 times a week) has some beneficial effects on inhibiting tumor growth. The combination of DS-437 and the anti-p185erbB2/neu?antibody 4D5 had even more dramatic effects[1]. | Animal Model: | Six to Ten weeks old female Balb/c mice (bearing ?CT26Her2 tumor cells)[1] | | Dosage: | 10 mg/kg | | Administration: | i.p.; 5 times a week | | Result: | Had some beneficial effects on inhibiting tumor growth. |
| [IC 50]
PRMT5; PRMT7 | [References]
[1] DAVID SMIL. Discovery of a Dual PRMT5–PRMT7 Inhibitor[J]. ACS Medicinal Chemistry Letters, 2015, 6 4: 408-412. DOI: 10.1021/ml500467h
[2] YASUHIRO NAGAI. PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targeted p185erbB2/neu Tumor Immunotherapy.[J]. Frontiers in Immunology, 2019: 174. DOI: 10.3389/fimmu.2019.00174 |
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Sigma-Aldrich
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Energy Chemical
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InvivoChem
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Merck KGaA
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www.sigmaaldrich.cn |
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