| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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Purity: ≥98%
AMD3465 hexahydrobromide (AMD-3465; GENZ-644494 6-HBr) is a novel monomacrocyclic antagonist of CXCR4 that has potential anticancer and anti-HIV activity. It effectively prevents CXCL12 from binding to SupT1 cells, with an IC50 of 18 nM. With an IC50 of 17 nM, AMD3465 blocks both MAPK phosphorylation and CXCL12-induced calcium signaling in SupT1 cells. However, in U87.CD4.CCR5 cells, AMD3465 was unable to inhibit the intracellular calcium fluxes induced by the CCR5 ligands RANTES, LD78β, and MIP-1β. AMD3465 inhibits the chemotaxis that human T-lymphoid SupT1 cells experience when exposed to CXCL12 and stops U87.CD4 cells from internalizing CXCR4 due to chemokines. Furthermore, AMD3465 exhibits activity against the X4 HIV-1 strains IIIB, NL4.3, RF, and HE, with an IC50 ranging from 6 to 12 nM. With an IC50 of 12.3 nM, AMD3465 inhibits the HIV-2 strains ROD and EHO.
| Targets |
12G5 mAb-CXCR4 ( IC50 = 1.1 nM ); CXCL12AF647-CXCR4 ( IC50 = 1.7 nM ); X4 HIV-1 (NL4.3) ( IC50 = 121 nM );
X4 HIV-1 (RF) ( IC50 = 1.1 nM ); X4 HIV-1 (HE) ( IC50 = 1.7 nM ); X4 HIV-1 (IIIB) ( IC50 = 121 nM ); X4 HIV-1 (NL4.3AMD3100) ( IC50 = 1.1 nM ); HIV-2 (ROD) ( IC50 = 1.7 nM ); HIV-2 (EHO) ( IC50 = 121 nM ) |
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
In order to conduct competition binding studies against CXCR4, a concentration range of AMD3465 is incubated for three hours at 4°C in binding buffer (PBS containing pH 7.4, 0.25% BSA, 1 mM CaCl2, and 5 ×105 CCRF-CEM cells) in Millipore DuraporeTM filter plates. Washing with cold 50 mM HEPES and 0.5 M NaCl pH 7.4 removes unbound 125I-SDF-1α. Membranes from CHO-S cells that express recombinant BLT1 are used for the competition binding assay against that protein. The membranes are prepared using mechanical cell lysis, high-speed centrifugation, resuspension in a buffer containing 50 mM HEPES and 5 mM MgCl2, and flash freezing. The assay mixture comprising 50 mM Tris, pH 7.4, 10 mM MgCl2, 10 mM CaCl2, 4 nM LTB4 combined with 1 nM 3H-LTB4, and 8 μg membrane is incubated with AMD3465 for 1 hour at room temperature. Filtration is used to separate the unbound 3H-LTB4 on Millipore Type GF-C filter plates. A Liquid Scintillation Counter (LKB Rackbeta 1209), is used to count the bound radioactivity. MCE has not independently verified these techniques' accuracy. They are merely meant to be used as references.
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| Cell Assay |
After a 24-hour serum starvation period, 1 μg/mL CXCL12, 2.5 ng/mL AMD 3465, 200 μM rolipram, or 10 μM forskolin are administered to astrocytes, granule cells, U87 cells, and Daoy cells. After 24 and 48 hours of treatment, respectively, trypan blue exclusion is used to measure the growth of Daoy and U87 cells in culture[2].
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| Animal Protocol |
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| References |
| Molecular Formula |
C24H44BR6N6
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| Molecular Weight |
896.07
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| Exact Mass |
410.32
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| Elemental Analysis |
C, 32.17; H, 4.95; Br, 53.50; N, 9.38
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| CAS # |
185991-07-5
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| Related CAS # |
AMD 3465; 185991-24-6
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| Appearance |
Solid powder
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| SMILES |
C1CNCCNCCCN(CCNC1)CC2=CC=C(C=C2)CNCC3=CC=CC=N3.Br.Br.Br.Br.Br.Br
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| InChi Key |
ARHBIBDGWDRBJH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H38N6.6BrH/c1-2-13-29-24(5-1)20-28-19-22-6-8-23(9-7-22)21-30-17-4-12-26-15-14-25-10-3-11-27-16-18-30;;;;;;/h1-2,5-9,13,25-28H,3-4,10-12,14-21H2;6*1H
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| Chemical Name |
N-(pyridin-2-ylmethyl)-1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methanamine;hexahydrobromide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.79 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 25.0 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: ≥ 2.5 mg/mL (2.79 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 100 mg/mL (111.60 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1160 mL | 5.5799 mL | 11.1598 mL | |
| 5 mM | 0.2232 mL | 1.1160 mL | 2.2320 mL | |
| 10 mM | 0.1116 mL | 0.5580 mL | 1.1160 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.
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