LLY-284 (LLY284) is a negative control and tool compound for LLY-283. It is a diastereomer of LLY-283 but was much less active. LLY-283 (LLY283) is the first-in-class and selective SAM-competitive inhibitor of PRMT5 (protein arginine methyltransferase 5) with antitumor activity. LLY-283 inhibited PRMT5 enzymatic activity in vitro and in cells with IC₅₀ values of 22 ± 3 and 25 ± 1 nM, respectively. LLY-283 also showed antitumor activity in mouse xenografts when dosed orally and can serve as an excellent probe molecule for understanding the biological function of PRMT5 in normal and cancer cells. PRMT5 is ubiquitously expressed in most tissues and its expression has been shown to be elevated in several cancers including breast cancer, gastric cancer, glioblastoma, and lymphoma. PRMTs binds to the lysine or arginine residues of substrate proteins via the substrate binding groove and SAM via the cofactor binding site.

Physicochemical Properties

Molecular Formula	C17H18N4O4
Molecular Weight	342.36
Exact Mass	342.132
CAS #	2226515-75-7
Related CAS #	LLY-283;2040291-27-6
PubChem CID	136213035
Appearance	White to off-white solid powder
LogP	0.2
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	25
Complexity	464
Defined Atom Stereocenter Count	5
SMILES	C1=CC=C(C=C1)[C@@H]([C@@H]2[C@H]([C@H]([C@@H](O2)N3C=CC4=C(N=CN=C43)N)O)O)O
InChi Key	WWOOWAHTEXIWBO-CNUKPYSBSA-N
InChi Code	InChI=1S/C17H18N4O4/c18-15-10-6-7-21(16(10)20-8-19-15)17-13(24)12(23)14(25-17)11(22)9-4-2-1-3-5-9/h1-8,11-14,17,22-24H,(H2,18,19,20)/t11-,12-,13+,14+,17+/m0/s1
Chemical Name	(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(S)-hydroxy(phenyl)methyl]oxolane-3,4-diol
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

ACS Med. Chem. Lett. (2018)DOI:10.1021/acsmedchemlett.8b00014

Solubility Data

Solubility (In Vitro)	DMSO: > 50 mg/mL Water:N/A Ethanol:N/A
Solubility (In Vivo)	N/A  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9209 mL	14.6045 mL	29.2090 mL
	5 mM	0.5842 mL	2.9209 mL	5.8418 mL
	10 mM	0.2921 mL	1.4605 mL	2.9209 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.