LQZ-7I (LQZ7I) is a novel survivin inhibitor and a malarial protease PfSUB1 inhibitor. The focus of this work is LQZ-7I, which demonstrated noticeably increased activity. When taken orally, LQZ-7 effectively slows the growth of xenograft tumors and causes tumors to lose survivin. The data obtained using LQZ-7I in both in vitro and in vivo studies highlight its potential as a lead for further development, which may result in a potential cancer therapeutic by directly targeting the survivin protein.
Physicochemical Properties
| Molecular Formula | C20H14F2N4 |
| Molecular Weight | 348.3488 |
| Exact Mass | 348.118 |
| Elemental Analysis | C, 68.96; H, 4.05; F, 10.91; N, 16.08 |
| CAS # | 195822-23-2 |
| Related CAS # | 195822-23-2 |
| PubChem CID | 468690 |
| Appearance | Light yellow to green yellow solid powder |
| LogP | 5.2 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 26 |
| Complexity | 396 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | DKPCKOKYSVPFEB-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H14F2N4/c21-13-5-9-15(10-6-13)23-19-20(24-16-11-7-14(22)8-12-16)26-18-4-2-1-3-17(18)25-19/h1-12H,(H,23,25)(H,24,26) |
| Chemical Name | 2-N,3-N-bis(4-fluorophenyl)quinoxaline-2,3-diamine |
| Synonyms | LQZ-7I; LQZ 7I; LQZ7I |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | survivin (IC50 = 4.8 µM); survivin (IC50 =3.1 µM) |
| ln Vitro | LQZ-7I exhibited enhanced cytotoxicity in comparison to its parent drug LQZ-7, as evidenced by its IC50 values of 3.1 μM on C4-2 cells and 4.8 μM on PC-3 cells [1]. Survivin expression is decreased with LQZ-7I (10 μM; 0–6 hours) treatment. LQZ-7I, however, did not lessen XIAP, CIAP1, or CIAP2 expression. LQZ-7I has a vocabulary and might be the intended target survivin [1]. |
| ln Vivo | LQZ-7I (100 mg/kg; gavaged every other day for ten tumor treatments) dramatically reduced growth in mice without causing any evident side effects in the mice[1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: PC-3 or C4-2 Cell Tested Concentrations: 10 µM Incubation Duration: 0-6 hrs (hours) Experimental Results: diminished survivin expression. |
| Animal Protocol |
Animal/Disease Models: 6weeks old male NSG mice[1]: 100 mg/kg; 200 µL vehicle (90% corn oil/10% DMSO) Route of Administration: po (oral gavage) once every other day, a total of 10 times Treatment Experimental Results: significant It Dramatically inhibited tumor growth without any significant side effects on the mice, and there was no change in body weight and physical strength. Wet weights of major organs at the end of the study. |
| References |
[1]. Synthesis and Identification of a Novel Lead Targeting Survivin Dimerization for Proteasome-Dependent Degradation. J Med Chem. 2020 Jun 9. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 70~125 mg/mL (201.0~358.8 mM) Ethanol: 70 mg/mL (~201.0 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8707 mL | 14.3534 mL | 28.7068 mL | |
| 5 mM | 0.5741 mL | 2.8707 mL | 5.7414 mL | |
| 10 mM | 0.2871 mL | 1.4353 mL | 2.8707 mL |