Isofistularin-3

Isofistularin-3 is a direct, DNA-competitive DNMT1 inhibitor, with an IC50 of 13.5 μM. Isofistularin-3, as a DNA demethylating agent, induces cell cycle arrest and sensitization to TRAIL in cancer cells. Isofistularin-3 can be used as an ADC cytotoxin.

Product information

Molecular Weight: 1114.01

Formula: C31H30Br6N4O11

Chemical Name: (5S, 10R)-7, 9-dibromo-N-[(2S)-3-{2, 6-dibromo-4-[(1S)-2-{[(5R, 10S)-7, 9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2, 6, 8-trien-3-yl]formamido}-1-hydroxyethyl]phenoxy}-2-hydroxypropyl]-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2, 6, 8-triene-3-carboxamide

Smiles: COC1=C(Br)[C@H](O)[C@]2(CC(=NO2)C(=O)NC[C@H](O)COC2C(Br)=CC(=CC=2Br)[C@H](O)CNC(=O)C2C[C@]3(C=C(Br)C(OC)=C(Br)[C@H]3O)ON=2)C=C1Br

InChiKey: TURTULDFIIAPTC-GIGRZPOESA-N

InChi: InChI=1S/C31H30Br6N4O11/c1-48-24-16(34)5-30(26(44)21(24)36)7-18(40-51-30)28(46)38-9-13(42)11-50-23-14(32)3-12(4-15(23)33)20(43)10-39-29(47)19-8-31(52-41-19)6-17(35)25(49-2)22(37)27(31)45/h3-6,13,20,26-27,42-45H,7-11H2,1-2H3,(H,38,46)(H,39,47)/t13-,20+,26-,27+,30+,31-/m0/s1

Technical Data

Appearance: Solid Power

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

Solubility: Soluble in DMSO

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:

Isofistularin-3 (1-50 μM; 24-72 hours) shows a marked reduction of cell proliferation. Isofistularin-3 (5-50 μM; 24 hours) increases arrests cancer cells in G0/G1 cell cycle phase. Isofistularin-3 (25 μM; 72 hours) increases AHR expression. Isofistularin-3 induces AHR promoter demethylation. Isofistularin-3 (72 hours) inhibits a broader panel of cancer cell lines proliferation, with the GI50s ranging from 7.3-14.8 μM. Isofistularin-3 induces morphological changes and autophagy in RAJI cells. Isofistularin-3 induces caspase-dependent and -independent cell death. Isofistularin-3 sensitizes lymphoma cells to TRAIL-induced apoptosis.

References:

1. Florean C, et al. Discovery and characterization of Isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to TRAIL in cancer cells. Oncotarget. 2016 Apr 26;7(17):24027-49.

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