CMLD-2

CMLD-2, an inhibitor of HuR-ARE interaction, competitively binds HuR protein disrupting its interaction with adenine-uridine rich elements (ARE)-containing mRNAs (Ki=350 nM). CMLD-2 induces apoptosis exhibits antitumor activity in different cancer cells as colon, pancreatic, thyroid and lung cancer cell lines. Hu antigen R (HuR) is an RNA binding protein, can regulate target mRNAs stability and translation.

Product information

CAS Number: 958843-91-9

Molecular Weight: 513.58

Formula: C31H31NO6

Chemical Name: 5, 7-dimethoxy-8-[1-(4-methoxyphenyl)-3-oxo-3-(pyrrolidin-1-yl)propyl]-4-phenyl-2H-chromen-2-one

Smiles: COC1C=C(OC)C(C(CC(=O)N2CCCC2)C2C=CC(=CC=2)OC)=C2OC(=O)C=C(C=12)C1C=CC=CC=1

InChiKey: PROGRNRRJJYCNX-UHFFFAOYSA-N

InChi: InChI=1S/C31H31NO6/c1-35-22-13-11-21(12-14-22)23(17-27(33)32-15-7-8-16-32)29-25(36-2)19-26(37-3)30-24(18-28(34)38-31(29)30)20-9-5-4-6-10-20/h4-6,9-14,18-19,23H,7-8,15-17H2,1-3H3

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 50 mg/mL (97.36 mM; Need ultrasonic)

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:

CMLD-2 (1-75 μM; 24-72 h) inhibits thyroid cancer cell viability. CMLD-2 (20-30 μM; 24-48 h) activates caspases and induces apoptotic cell death in H1299 and A549 cells. CMLD-2 (30 μM; 24-48 h) induces G1 cell cycle arrest and mitochondrial perturbation in H1299 and A549 cell. CMLD-2 (30 μM; 24-48 h) reduces expression of HuR and HuR-regulated mRNAs and proteins in H1299 cells. CMLD-2 (35 μM; 72 h) decreases directional migration capability in SW1736, 8505C, BCPAP and K1 cells. CMLD-2 induces a strong decrease of MAD2 mRNA levels in SW1736, 8505C, BCPAP and K1 cells.

References:

1. Wu X, et, al. Identification and validation of novel small molecule disruptors of HuR-mRNA interaction. ACS Chem Biol. 2015 Jun 19;10(6):1476-84.
2. Allegri , et, al. The HuR CMLD-2 inhibitor exhibits antitumor effects via MAD2 downregulation in thyroid cancer cells. Sci Rep. 2019 May 14;9(1):7374.
3. Muralidharan R, et, al. HuR-targeted small molecule inhibitor exhibits cytotoxicity towards human lung cancer cells. Sci Rep. 2017 Aug 30;7(1):9694.

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