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DS-437

Names

[ CAS No. ]:
1674364-87-4

[ Name ]:
DS-437

[Synonym ]:
9-[(2ξ)-5-S-{2-[(Ethylcarbamoyl)amino]ethyl}-5-thio-β-D-threo-pentofuranosyl]-9H-purin-6-amine
DS-437
5'-S-[2-[[(Ethylamino)carbonyl]amino]ethyl]-5'-thio-adenosine
9H-Purin-6-amine, 9-[(2ξ)-5-S-[2-[[(ethylamino)carbonyl]amino]ethyl]-5-thio-β-D-threo-pentofuranosyl]-

Biological Activity

[Description]:

DS-437 is a potent, selective, dual inhibitor of PRMT5 and PRMT7 with IC50 of 6.0 uM for both, DS-437 is inactive against 29 other human protein-, DNA-, and RNA-methyltransferases; inhibits methylation of full-length histone 4 by PRMT5-MEP50 with an IC50 of 37 ± 1.2 μM in a biochemical assay; inhibits symmetrical dimethylation of PRMT5 substrates in cells.

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Epigenetics >> Histone Methyltransferase
Research Areas >> Inflammation/Immunology

[In Vitro]

DS-437 was able to inhibit methylation of an H4[1–24] peptide by the PRMT5–MEP50 complex under balanced conditions (cofactor and substrate concentrations set at their respective Km values) in a dose-dependent manner with an IC50 of 5.9 ± 1.4 μM[1]. DS-437 increased total CD8+ and CD8+ PD-1+ T cells[2].

[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.

[References]

[1]. Smil D, et al. Discovery of a Dual PRMT5-PRMT7 Inhibitor.ACS Med Chem Lett. 2015 Mar 2;6(4):408-12.

[2]. Nagai Y, et al. PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targetedp185erbB2/neu Tumor Immunotherapy.Front Immunol. 2019 Feb 8;10:174.

Chemical & Physical Properties

[ Density]:
1.7±0.1 g/cm3

[ Molecular Formula ]:
C15H23N7O4S

[ Molecular Weight ]:
397.453

[ Exact Mass ]:
397.153229

[ LogP ]:
0.16

[ Index of Refraction ]:
1.776

[ Storage condition ]:
2-8°C

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
Missing Phrase - N15.00950417

[ RIDADR ]:
UN 2811 6.1 / PGIII

Related Compounds