ALX 40-4C is a novel and potent peptide inhibitor of CXCR4 which inhibits the binding of SDF-1 to CXCR4 with a Ki of 1 μM.
Physicochemical Properties
| Molecular Formula | C₅₆H₁₁₃N₃₇O₁₀ |
| Molecular Weight | 1464.74 |
| Exact Mass | 1469.621 |
| CAS # | 143413-49-4 |
| Related CAS # | ALX 40-4C Trifluoroacetate |
| PubChem CID | 168009823 |
| Sequence | Ac-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-NH2 |
| SequenceShortening | Ac-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-NH2 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 0 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 34 |
| Rotatable Bond Count | 49 |
| Heavy Atom Count | 103 |
| Complexity | 2190 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(N)(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(C)=O |
| InChi Key | RUWHAENIXFIHPU-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H29NO7.C17H24N2O7.C17H22O9.C16H24O9/c1-18(2,13-26-15(21)8-7-14(20)24-3)16(22)17(23)25-12-11-19-9-5-4-6-10-19;1-17(2,11-26-14(21)6-5-13(20)24-3)15(22)16(23)25-10-4-8-19-9-7-18-12-19;1-10-12(26-11(2)25-10)8-23-16(21)15(20)17(3,4)9-24-14(19)7-6-13(18)22-5;1-10(2)14(20)24-9-25-15(21)13(19)16(3,4)8-23-12(18)7-6-11(17)22-5/h7-8,16,22H,4-6,9-13H2,1-3H3;5-7,9,12,15,22H,4,8,10-11H2,1-3H3;6-7,15,20H,2,8-9H2,1,3-5H3;6-7,10,13,19H,8-9H2,1-5H3 |
| Chemical Name | 4-O-[3-hydroxy-2,2-dimethyl-4-[(5-methyl-2-methylidene-1,3-dioxol-4-yl)methoxy]-4-oxobutyl] 1-O-methyl but-2-enedioate;4-O-[3-hydroxy-2,2-dimethyl-4-(2-methylpropanoyloxymethoxy)-4-oxobutyl] 1-O-methyl but-2-enedioate;4-O-[3-hydroxy-2,2-dimethyl-4-oxo-4-(2-piperidin-1-ylethoxy)butyl] 1-O-methyl but-2-enedioate;4-O-[3-hydroxy-4-(3-imidazol-1-ylpropoxy)-2,2-dimethyl-4-oxobutyl] 1-O-methyl but-2-enedioate |
| Synonyms | ALX 40-4C ALX-40-4C ALX40-4C |
| 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
| ln Vitro | ALX 40-4C is a little peptide that interacts with the second extracellular loop of the chemokine receptor CXCR4 to selectively suppress infection by preventing viruses from directly interacting with CXCR4 [1]. With EC50 values of 0.34 ± 0.04 μg/mL and 0.37 ± 0.01 μg/mL for HIV-1 NL4-3 and NC10, respectively, ALX 40-4C demonstrates a strong anti-HIV-1 action. For HIV-1 HXB2 and HC43, the EC50 is 0.34 ± 0.04 μg/mL and 0.06 ± 0.02 μg/mL, respectively, while the CC50 (50 percent cytotoxic threshold) is 21 μg/mL. In addition, ALX 40-4C demonstrated strong efficacy against env recombinant HIV, with EC50s for HIV-1 NL4-3 env and NC10 of 0.38 ± 0.01 μg/mL and 0.40 ± 0.0 μg/mL, respectively. For HIV-1 HXB2 env, the EC50 is 1.02 μg/mL, HC43 is ± 0.29 μg/mL, and the CC50 is 21 μg/mL[2]. ALX 40-4C exhibits an IC50 of 2.9 μM for binding to APJ. HIV-1 gp120/APJ-mediated cell membrane fusion is inhibited by ALX 40-4C, with IC50 values for the IIIB isolate being 3.41 μM and the 89.6 isolate being 3.1 μM, respectively [3]. |
| References |
[1]. Safe use of the CXCR4 inhibitor ALX40-4C in humans. AIDS Res Hum Retroviruses. 2001 Apr 10;17(6):475-86. [2]. HIV-1 resistance to the gp41-dependent fusion inhibitor C-34. Antiviral Res. 2003 Jul;59(2):137-42. [3]. Binding of ALX40-4C to APJ, a CNS-based receptor, inhibits its utilization as a co-receptor by HIV-1. Virology. 2003 Jul 20;312(1):196-203. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6827 mL | 3.4136 mL | 6.8272 mL | |
| 5 mM | 0.1365 mL | 0.6827 mL | 1.3654 mL | |
| 10 mM | 0.0683 mL | 0.3414 mL | 0.6827 mL |