HLI373

HLI373 is an efficacious Hdm2 inhibitor. HLI373 inhibits the ubiquitin ligase activity of Hdm2. HLI373 is effective in inducing apoptosis of several tumor cells that are sensitive to DNA-damaging agents. Antimalarial activity.

Product information

CAS Number: 502137-98-6

Molecular Weight: 341.41

Formula: C18H23N5O2

Chemical Name: 5-{[3-(dimethylamino)propyl]amino}-3, 10-dimethyl-2H, 3H, 4H, 10H-pyrimido[4, 5-b]quinoline-2, 4-dione

Smiles: CN(C)CCCNC1=C2C(=NC(=O)N(C)C2=O)N(C)C2=CC=CC=C21

InChiKey: LNRUPMPQQGPSQT-UHFFFAOYSA-N

InChi: InChI=1S/C18H23N5O2/c1-21(2)11-7-10-19-15-12-8-5-6-9-13(12)22(3)16-14(15)17(24)23(4)18(25)20-16/h5-6,8-9,19H,7,10-11H2,1-4H3

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: ≥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:

HLI373 (3-15 μM; 15 hours) selectively kills tumor cells harboring wild type p53[1]. HLI373 (10-50 μM) stabilizes cellular Hdm2 in a dose-dependent manner. HLI373 (3 μM) activates p53 transcription. HLI373 selectively inhibits auto-ubiquitylation of Hdm2. Co-transfection with plasmids encoding p53 and Hdm2 results in degradation of p53. Incubation with HLI373 (5-10 μM; 8 hours) blocks p53 degradation. HLI373 increases p53 and Hdm2 protein levels in cells. HLI 373 also shows lower IC50 values (below 6 μM) against both chloroquine-sensitive P. falciparum D6 strain (PfD6) and chloroquine-resistant P. falciparum W2 strain (PfW2) and exhibits early growth inhibition. HLI-373 is a MDM2 inhibitor interrupting its ubiquitin E3 ligase activity, could abolish the ubiquitylation of its substrate protein p53. HLI-373 targets the C-terminus functioning as an E3 ubiquitin ligase.

References:

1. Jirouta Kitagaki, et al. Targeting Tumor Cells Expressing p53 With a Water-Soluble Inhibitor of Hdm2. Mol Cancer Ther. 2008 Aug;7(8):2445-54.
2. Jagrati Jain, et al. Inhibitors of Ubiquitin E3 Ligase as Potential New Antimalarial Drug Leads. BMC Pharmacol Toxicol. 2017 Jun 2;18(1):40.
3. Ying Chen, et al. MDM2 Promotes Epithelial-Mesenchymal Transition and Metastasis of Ovarian Cancer SKOV3 Cells. Br J Cancer. 2017 Oct 10;117(8):1192-1201.

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