详情描述
SGC0946 is a highly potent and selective inhibitor of DOT1L methyltransferase. It selectively blocks binding of the cofactor, S-adenosylmethionine, to DOT1L, and inhibits the enzyme with an IC50 of 0.3 nM in a radioactive enzyme assay and is over 100-fold selective for other histone methyltransferases/HMTs. SGC0946 potently reduces H3K79 dimethylation with cellular IC50 of 2.6 nM in A431 cells, and 8.8 nM in MCF10A cells, which potently and selectively kills cells containing an MLL translocation. SGC0946 is much more potent than its close analog EPZ004777, and serves as an excellent chemical probe for investigating DOT1L and further development of DOT1L inhibitors for cancer therapy.
Product information
CAS Number: 1561178-17-3
Molecular Weight: 618.57
Formula: C28H40BrN7O4
Chemical Name: 1-(3-((((2R,3S,4R,5R)-5-(4-amino-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea
Smiles: CC(C)N(C[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=C(Br)C2=C1N=CN=C2N)CCCNC(=O)NC1C=CC(=CC=1)C(C)(C)C
InChiKey: IQCKJUKAQJINMK-HUBRGWSESA-N
InChi: InChI=1S/C28H40BrN7O4/c1-16(2)35(12-6-11-31-27(39)34-18-9-7-17(8-10-18)28(3,4)5)14-20-22(37)23(38)26(40-20)36-13-19(29)21-24(30)32-15-33-25(21)36/h7-10,13,15-16,20,22-23,26,37-38H,6,11-12,14H2,1-5H3,(H2,30,32,33)(H2,31,34,39)/t20-,22-,23-,26-/m1/s1
Technical Data
Appearance: Solid Power.
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO up to 100 mM
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥360 days if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
In Vitro:
SGC0946 was used at 1-5 µM final concentration in vitro and in cellular assays.
In Vivo:
SGC0946 was delivered via subcutaneously implanted mini-osmotic pumps capable of continuous infusion (drug load is ~50 mg/ml solution) for a period of 7 days in animal models.
References:
- Yu W, et al. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. (2012) Nat Commun. 3:1288.
- Yu W, et al. Bromo-deaza-SAH: A potent and selective DOT1L inhibitor. (2013) Bioorg Med Chem. 21(7):1787-94.
Products are for research use only. Not for human use.