PYZD-4409, Ubiquitin-activating Enzyme (E1) Inhibitor

PYZD-4409 is a novel potent, selective and cell permeable inhibitor of ubiquitin-activating enzyme (E1). It induces cell death in hematologic malignant cell lines and primary patient samples preferentially over normal hematopoietic cells. PYZD-4409 blocks degradation of the short-lived proteins p53 and cyclin D3. It inhibits NF-κB activation and induces cell death associated with ER stress. It also displays antitumor effects in a mouse model of leukemia by intraperitoneal administration of the drug.

Product information

CAS Number: 423148-78-1

Molecular Weight: 351.67

Formula: C14H7ClFN3O5

Chemical Name: 1-(3-Chloro-4-fluorophenyl)-4-[(5-nitro-2-furanyl)methylene]-3,5-pyrazolidinedione

Smiles: [O-][N+](=O)C1=CC=C(C=C2C(=O)NN(C3=CC(Cl)=C(F)C=C3)C2=O)O1

InChiKey: MSYMKEYWUWVZQY-RMKNXTFCSA-N

InChi: InChI=1S/C14H7ClFN3O5/c15-10-5-7(1-3-11(10)16)18-14(21)9(13(20)17-18)6-8-2-4-12(24-8)19(22)23/h1-6H,(H,17,20)/b9-6+

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 100 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: ≥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:

PYZD-4409 was used at 10-30 µM final concentration in various in vitro assays.

In Vivo:

PYZD-4409 was dosed intraperitoneally to the mouse model of leukemia (MDAY-D2 murine leukemia cells) at 10 mg/kg once per day.

References:

1. Xu GW, et al. The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. (2010) Blood. 115(11):2251-9.

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