ZZW-115 is a potent NUPR1 inhibitor, with a Kd of 2.1 μM. ZZW-115 induces tumor cell death by necroptosis and apoptosis. Anticancer activity.

Product information

CAS Number: 801991-87-7

Molecular Weight: 464.59

Formula: C24H31F3N4S

Chemical Name: dimethyl[2-(4-{3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl}piperazin-1-yl)ethyl]amine

Smiles: CN(C)CCN1CCN(CCCN2C3=CC=CC=C3SC3=CC=C(C=C23)C(F)(F)F)CC1

InChiKey: HUDONDPCYIGAMQ-UHFFFAOYSA-N

InChi: InChI=1S/C24H31F3N4S/c1-28(2)12-13-30-16-14-29(15-17-30)10-5-11-31-20-6-3-4-7-22(20)32-23-9-8-19(18-21(23)31)24(25,26)27/h3-4,6-9,18H,5,10-17H2,1-2H3

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:

ZZW-115 (0.1-33 μM; 72 hours) is efficient in killing cancer cells, with an IC50 in the range of 0.84 μM (ANOR) to 4.93 μM (HN14). ZZW-115 (0-100 μM; 24-72 hours) is efficient to kill these tumor cells with an IC50 in the range of 0.42 μM (Hep2G cells) to 7.75 μM (SaOS-2 cells). ZZW-115 induces pancreatic cell death by necrosis and apoptosis. ZZW-115 treatment induces a decrease in ATP production and induces a ROS overproduction. LDH release is significantly higher in ZZW-115-treated cells (MiaPaCa-2, 02-063, LIPC, Foie8b, and HN14 cells) than in control cells in a concentration-dependent manner. Similarly, caspase 3/7 activity is also greater in ZZW-115-treated cells. These experiments demonstrated that ZZW-115 exerted both pronecrotic and proapoptotic effects.

In Vivo:

ZZW-115 (0.5-5 mg/kg; injection; daily for 30 days) inhibits the growth of pancreatic xenografted tumors. ZZW-115 (5 mg/kg for 30 days; immunocompetent C57BL/6 mice were orthotopically implanted with Panc02 cells) treatment shows the tumor size is almost unmeasurable in some cases.

References:

1. Santofimia-Castaño P, et al. Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis. J Clin Invest. 2019;129(6):2500-2513. Published 2019 Mar 28.
2. Santofimia-Castaño P, et al. Targeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma. Cells. 2019;8(11):1453. Published 2019 Nov 17.

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