UNBS-5162

UNBS5162 is a novel naphthalimide that binds to DNA by intercalation and suppresses CXCL chemokine elaboration. In vivo UNBS5162 after repeat administration significantly increased survival in orthotopic human prostate cancer models. Results obtained by the National Cancer Institute (NCI) using UNBS3157 and UNBS5162 against the NCI 60 cell line panel did not show a correlation with any other compound present in the NCI database, including amonafide, thereby suggesting a unique mechanism of action for these two novel naphthalimides.

Product information

CAS Number: 956590-23-1

Molecular Weight: 326.35

Formula: C17H18N4O3

Chemical Name: 1-(2-(2-(dimethylamino)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)urea

Smiles: CN(C)CCN1C(=O)C2C=C(C=C3C=CC=C(C3=2)C1=O)NC(N)=O

InChiKey: WCKZRLOUKYFJDY-UHFFFAOYSA-N

InChi: InChI=1S/C17H18N4O3/c1-20(2)6-7-21-15(22)12-5-3-4-10-8-11(19-17(18)24)9-13(14(10)12)16(21)23/h3-5,8-9H,6-7H2,1-2H3,(H3,18,19,24)

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO: 21.5 mg/mL

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: Powder -20^oC 3 years 4^oC 2 years In solvent -80^oC 6 months -20^oC 1 month

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

The mean antiproliferative activity IC50 values determined against nine human cancer cell lines investigated (using the MTT colorimetric assay) were 19.8 and 17.9 μM for UNBS3157 and UNBS5162, respectively.

In Vivo:

In the PC-3 model, UNBS3157 displayed appreciable activity against PC-3 prostate carcinoma when administered orally at 160 mg/kg (%T/C: 151%, P = .03) but not at the lower dose of 40 mg/kg (%T/C: 100%). Repeat i.v. administration of the compound at 10 mg/kg (three times a week for 6 consecutive weeks) contributed therapeutic benefits that were similar to repeat i.v. administration (once a week for 6 consecutive weeks) of 20-mg/kg taxol in the PC-3 orthotopic model. UNBS5162 was administered in a 3 + 3 dose escalation scheme by intravenous infusion over 1 h weekly for 3 weeks of a 4-week cycle. Safety, serial serum PK and tolerability were captured throughout the study. Response Evaluation Criteria in Solid Tumors was utilized every 2 cycles to assess for anti-tumor response.

References:

1. Mijatovic T, et al. UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers. Neoplasia. 2008 Jun;10(6):573-86.
2. Mahadevan D, et al. Phase I trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma. Int J Clin Oncol. 2013 Oct;18(5):934-41.

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