ANI-7 is an activator of aryl hydrocarbon receptor (AhR) pathway. ANI-7 inhibits the growth of multiple cancer cells, and potently and selectively inhibits the growth of MCF-7 breast cancer cells with a GI50 of 0.56 μM. ANI-7 induces CYP1-metabolizing mono-oxygenases by activating AhR pathway, and also induces DNA damage, checkpoint Kinase 2 (Chk2) activation, S-phase cell cycle arrest, and cell death in sensitive breast cancer cell lines.

Product information

CAS Number: 931417-26-4

Molecular Weight: 263.12

Formula: C13H8Cl2N2

Chemical Name: (2Z)-2-(3,4-dichlorophenyl)-3-(1H-pyrrol-2-yl)prop-2-enenitrile

Smiles: N#C/C(=C\C1=CC=CN1)/C1C=C(Cl)C(Cl)=CC=1

InChiKey: IJJHHDLGGYDXGD-UXBLZVDNSA-N

InChi: InChI=1S/C13H8Cl2N2/c14-12-4-3-9(7-13(12)15)10(8-16)6-11-2-1-5-17-11/h1-7,17H/b10-6+

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 20.83 mg/mL (79.17 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: ≥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:

ANI-7 (2.5 μM; 24 hours; MCF10A and MDA-MB-468 cells) treatment induces significant S-phase and G2 + M-phase cell cycle arrest within 24 hours of treatment in MDA-MB-468 cells, and negligible effect in normal breast MCF10A cells. ANI-7 (2 μM; 12-24 hours; MDA-MB-468 cells) treatment results in a significant increase in the content and phosphorylation of CHK2, and induces a significant increase in H2AXɣ in MDA-MB-468 cells, indicative of DNA double-strand damage. Inhibition of the AhR pathway ameliorates the effects of ANI-7. ANI-7 activates XRE activity and expression of the AhR and CYP1 members. Comparisons of the GI50 values show that ANI-7 produces a GI50 value of 0.38 μM in MCF-7 cells, whereas values of 3.0-42 μM are observed in cell lines from lung, colon, ovary, neuronal, glial, prostate, and pancreas. The only other tumor type that shows appreciable growth inhibition by ANI-7 is the A431 vulva cell line (GI50 of 0.51μM). ANI-7 potently inhibits the growth of T47D, ZR-75-1, MCF-7, SKBR3, and MDA-MB-468 breast cancer cells (GI50 range of 0.16-0.38 μM), moderately inhibits the growth of BT20 and BT474 cells (GI50 range of 1-2 μM), and essentially fails to inhibit the growth of MDA-MB-231 and MCF10A cells (GI50 range of 17-26 μM). Moreover, ANI-7 maintained its ability to inhibit the growth of drug-resistant cells (MCF-7/VP16: GI50 of 0.21 μM).

References:

1. ilbert J, et al. (Z)-2-(3,4-Dichlorophenyl)-3-(1H-Pyrrol-2-yl)Acrylonitrile Exhibits Selective Antitumor Activity in Breast Cancer Cell Lines via the Aryl Hydrocarbon Receptor Pathway. Mol Pharmacol. 2018 Feb;93(2):168-177.
2. Baker JR, et al. Dichlorophenylacrylonitriles as AhR Ligands That Display Selective Breast Cancer Cytotoxicity in vitro. ChemMedChem. 2018 Jul 18;13(14):1447-1458.
3. Mark Tarleton, et al. Library synthesis and cytotoxicity of a family of 2-phenylacrylonitriles and discovery of an estrogen dependent breast cancer lead compound.  Medicinal Chemistry Communication. January 20112. (1):31-37.

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