| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
CXCR4
USL311 targets CXCR4 (C-X-C chemokine receptor type 4), a G protein-coupled receptor that binds its natural ligand, stromal cell-derived factor-1 (SDF-1, also known as CXCL12). The SDF-1/CXCR4 axis plays a critical role in tumor progression, angiogenesis, metastasis, and immune cell trafficking. CXCR4 is overexpressed in many cancers and is associated with poor prognosis and resistance to therapy. By antagonizing CXCR4, USL311 prevents SDF-1 from binding to the receptor, thereby inhibiting downstream signaling pathways that promote tumor cell migration, invasion, and survival. USL311 is a selective CXCR4 antagonist. |
|---|---|
| ln Vitro |
In vitro, USL311 is a potent and selective CXCR4 antagonist. The compound prevents the binding of SDF-1/CXCL12 to CXCR4. Its antagonistic activity has been characterized in cell-based assays measuring CXCR4-mediated signaling, including calcium mobilization, cell migration, and chemotaxis. The compound's selectivity for CXCR4 over other chemokine receptors has been confirmed.
|
| ln Vivo |
In vivo, USL311 has anti-tumor activity. By blocking the SDF-1/CXCR4 axis, the compound inhibits tumor progression, angiogenesis, and metastasis. USL311 has been evaluated in preclinical models of cancer. Its ability to inhibit tumor growth and metastasis has been demonstrated in xenograft models. The compound has also been studied in clinical trials for various cancers.
|
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for USL311 involve measuring its binding affinity to CXCR4. Radioligand binding assays using membrane preparations from cells expressing CXCR4 are performed with a radiolabeled CXCR4 ligand (e.g., [¹²⁵I]-SDF-1 or a small molecule CXCR4 antagonist) and varying concentrations of USL311. Binding affinity (IC50 or Ki) is determined by competitive displacement.
|
| Cell Assay |
In vitro cell-based experiments for USL311 are conducted using cancer cell lines that express CXCR4. Cells are treated with USL311 at varying concentrations, and cell migration and invasion are assessed using Boyden chamber or transwell assays. Calcium mobilization is measured using fluorescent calcium indicators to assess CXCR4 signaling inhibition. Cell proliferation and survival are assessed using standard viability assays.
|
| Animal Protocol |
In vivo animal experiments for USL311 are performed in xenograft mouse models of cancer. USL311 is administered, and tumor growth, metastasis, and angiogenesis are assessed. The compound's ability to inhibit tumor progression and improve survival is evaluated. Clinical trials in humans have also been conducted for various cancers.
|
| ADME/Pharmacokinetics |
USL311 is a small molecule (MW 422.57, formula C24H34N6O) with suitable physicochemical properties for oral administration. Detailed pharmacokinetic parameters, including bioavailability, half-life, and clearance, are available from preclinical and clinical studies. Its favorable PK properties support its use in in vivo efficacy studies.
|
| Toxicity/Toxicokinetics |
Preclinical and clinical toxicology studies have been conducted to evaluate the safety profile of USL311. The compound is generally well-tolerated at therapeutic doses. Clinical trials have evaluated the safety and efficacy of USL311 in cancer patients. The safety profile supports its continued development as an anticancer agent.
|
| References | |
| Additional Infomation |
USL-311 is currently undergoing clinical trial NCT02765165 (a phase I/II study of USL-311 as monotherapy and in combination with lomustine in patients with advanced solid tumors and recurrent/recurrent glioblastoma (GBM)). The CXCR4 antagonist USL-311 is an orally bioavailable CXC chemokine receptor 4 (CXCR4) inhibitor with potential antitumor activity. After administration, USL-311 binds to CXCR4, thereby preventing the binding of stromal cell-derived factor-1 (SDF-1 or CXCL12) to CXCR4 and inhibiting CXCR4 activation, which may lead to reduced proliferation and migration of CXCR4-expressing tumor cells. CXCR4 is a chemokine receptor belonging to the G protein-coupled receptor (GPCR) family, playing an important role in chemotaxis and angiogenesis, and is upregulated in various tumor cell types.
USL311 is also known as USL-311. It is a potent and selective CXCR4 antagonist with anti-tumor activity. The compound has been investigated in preclinical and clinical studies for the treatment of various cancers. Its ability to block the SDF-1/CXCR4 axis and inhibit tumor progression makes it a promising therapeutic agent. The compound is not approved for clinical use. |
| Molecular Formula |
C24H34N6O
|
|---|---|
| Molecular Weight |
422.566364765167
|
| Exact Mass |
422.28
|
| Elemental Analysis |
C, 68.22; H, 8.11; N, 19.89; O, 3.79
|
| CAS # |
1373268-67-7
|
| PubChem CID |
56961879
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
31
|
| Complexity |
558
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
XNUNVQKARNSSEO-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H34N6O/c1-19(2)28-15-9-21(10-16-28)29-13-4-14-30(18-17-29)23-6-3-5-22(27-23)24(31)26-20-7-11-25-12-8-20/h3,5-8,11-12,19,21H,4,9-10,13-18H2,1-2H3,(H,25,26,31)
|
| Chemical Name |
6-[4-(1-propan-2-ylpiperidin-4-yl)-1,4-diazepan-1-yl]-N-pyridin-4-ylpyridine-2-carboxamide
|
| Synonyms |
USL 311; USL-311; USL311
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ~18.6 mg/mL (~44.0 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3665 mL | 11.8324 mL | 23.6647 mL | |
| 5 mM | 0.4733 mL | 2.3665 mL | 4.7329 mL | |
| 10 mM | 0.2366 mL | 1.1832 mL | 2.3665 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02765165 | Terminated | Drug: USL311 Drug: Lomustine |
Solid Tumors (Phase 1) Relapsed/Recurrent GBM (Phase 2) |
Proximagen, LLC | April 2016 | Phase 1 Phase 2 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
