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Purity: ≥98%
AMD3465 (AMD-3465) is a novel monomacrocyclic antagonist of CXCR4 with 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 = 0.75 nM ); CXCL12AF647-CXCR4 ( IC50 = 18 nM ); X4 HIV-1 (IIIB) ( IC50 = 12.3 nM ); X4 HIV-1 (NL4.3) ( IC50 = 6.1 nM ); X4 HIV-1 (NL4.3AMD3100) ( IC50 = 2822 nM ); X4 HIV-1 (RF) ( IC50 = 7.4 nM ); X4 HIV-1 (HE) ( IC50 = 9.8 nM ); HIV-2 (ROD) ( IC50 = 12.3 nM ); HIV-2 (EHO) ( IC50 = 12.3 nM )
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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 |
C24H38N6
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| Molecular Weight |
410.10
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| Exact Mass |
410.32
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| Elemental Analysis |
C, 70.20; H, 9.33; N, 20.47
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| CAS # |
185991-24-6
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| Related CAS # |
AMD 3465 hexahydrobromide; 185991-07-5
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| Appearance |
Solid powder
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| SMILES |
C1CNCCNCCCN(CCNC1)CC2=CC=C(C=C2)CNCC3=CC=CC=N3
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| InChi Key |
CWJJHESJXJQCJA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H38N6/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
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| Chemical Name |
N-(pyridin-2-ylmethyl)-1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methanamine
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| Synonyms |
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| HS Tariff Code |
2934.99.03.00
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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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4384 mL | 12.1921 mL | 24.3843 mL | |
| 5 mM | 0.4877 mL | 2.4384 mL | 4.8769 mL | |
| 10 mM | 0.2438 mL | 1.2192 mL | 2.4384 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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