UNC1215 --- L3MBTL3 Domain Inhibitor

UNC1215 is a highly potent and selective small molecule inhibitor for the methyl-lysine (Kme) reading function of L3MBTL3, a member of the malignant brain tumor (MBT) family of chromatin-interacting transcriptional repressors. UNC1215 binds to L3MBTL3 with a Kd of 120 nM (IC50 ~ 20 nM), competitively displacing mono- or dimethyl-lysine-containing peptides, and is greater than 50-fold more potent toward L3MBTL3 than other members of the MBT family. It also displays >100-fold selectivity over a panel of more than 200 histone methyltransferases, kinases, ion channels and 7-TM receptors. In cells, UNC1215 is nontoxic and directly binds to L3MBTL3 via the Kme-binding pocket of the MBT domains. It increases the cellular mobility of GFP-L3MBTL3 fusion proteins, and point mutants that disrupt the Kme-binding function of GFP-L3MBTL3 phenocopy the effects of UNC1215 on localization. UNC1215 was used to reveal a new Kme-dependent interaction of L3MBTL3 with BCLAF1, a protein implicated in DNA damage repair and apoptosis. UNC1215 can serve as a useful chemical tool to interrogate the functions of MBT proteins and probe methyl-lysine reader proteins as a target class.

Product information

CAS Number: 1415800-43-9

Molecular Weight: 529.72

Formula: C32H43N5O2

Chemical Name: (2-(phenylamino)-1,4-phenylene)bis((4-(pyrrolidin-1-yl)piperidin-1-yl)methanone)

Smiles: O=C(C1=CC=C(C=C1NC1C=CC=CC=1)C(=O)N1CCC(CC1)N1CCCC1)N1CCC(CC1)N1CCCC1

InChiKey: PQOOIERVZAXHBP-UHFFFAOYSA-N

InChi: InChI=1S/C32H43N5O2/c38-31(36-20-12-27(13-21-36)34-16-4-5-17-34)25-10-11-29(30(24-25)33-26-8-2-1-3-9-26)32(39)37-22-14-28(15-23-37)35-18-6-7-19-35/h1-3,8-11,24,27-28,33H,4-7,12-23H2

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 50 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: ≥12 months 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:

UNC1215 was used at 1-5 µM final concentration in vitro and in cellular assays.

References:

1. James Li, et al. Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain. (2013) Nat Chem Biol. 9(3):184-91.

Products are for research use only. Not for human use.

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