| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Kd: 65 pM (HGF)[1]
Dihexa targets the hepatocyte growth factor (HGF)/c-Met system. It binds to HGF with high affinity (Kd = 65 pM) and potentiates its activity at the c-Met receptor. By activating the HGF/c-Met pathway, dihexa promotes synaptogenesis and has neurotrophic activity. It is seven orders of magnitude more potent than brain-derived neurotrophic factor (BDNF) in neurotrophic activity assays. |
|---|---|
| ln Vitro |
Dihexa (PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a novel, potent, oral, brain-permeable oligopeptide drug derived from angiotensin IV that binds with high affinity (Kd = 65 pM) to hepatocyte growth factor (HGF) and potentiates its activity at its receptor, c-Met. Both dihexa and its
parent compound Norleucine 1-AngIV induce c-Met phosphorylation in the
presence of subthreshold concentrations of HGF and augment HGF-dependent
cell scattering. Further, dihexa and Nle1-AngIV induce hippocampal
spinogenesis and synaptogenesis similar to HGF itself. Dihexa
effectively inhibits HGF dimerization at 1 μM. While dihexa at 1 nM and
10 pM alone does not activate c-Met, it markedly augments the capacity
of HGF at 1.25 and 2.5 ng/mL to activate c-Met[1].
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| ln Vivo |
Dihexa has a long circulating half-life. Dihexa exhibits
procognitive activity. Dihexa reverses scopolamine-dependent spatial
learning deficits. It improves spatial learning in aged rats. Dihexa
induces spinogenesis in cultured hippocampal neurons[2].
|
| Enzyme Assay |
In vitro receptor binding assays for dihexa measure its binding affinity to HGF using surface plasmon resonance or other biophysical methods. A Kd of 65 pM is determined. Functional assays measure HGF/c-Met pathway activation by assessing c-Met phosphorylation or downstream signaling in cells treated with the compound.
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| Cell Assay |
In vitro cell-based assays for dihexa assess its neurotrophic and synaptogenic activity. Neuronal cultures are treated with serial dilutions of the compound, and synaptogenesis is assessed by measuring synaptic marker expression, dendritic spine density, or neuronal connectivity. Neurotrophic activity is compared to BDNF.
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| Animal Protocol |
Rats: Serial dilutions of dihexa in 50% DMSO or water (for
dilutions of 50 μg/mL or less) are prepared from the stock used to dose
the animals to be used for preparation of a standard curve. 10 μL of
each serial dilution is then added to 90 μL of blank plasma for final
concentrations of 0.01, 0.02, 0.05, 0.1, 0.2, 1, 10, 20, 50, and 100
μg/mL. 80 μL of each plasma sample is transferred to previously prepared
tubes containing 240 μL of ice-cold acetonitrile and vortexed
vigorously. 10 μL of isotonic saline containing 100 μg/mL Nle-YI-(6)
aminohexanoic amide as an internal standard is added to each sample on
ice. The standard-curve plasma samples are then stored at 20°C and
further processed alongside the pharmacokinetic study samples[2].
|
| ADME/Pharmacokinetics |
Dihexa has a molecular formula of C27H44N4O5 and a molecular weight of 504.67 g/mol. It is an oligopeptide drug and is also known as PNB-0408, Hexanoyl-Tyr-Ile-Ahx-NH2, and 6-[(2S,3S)-2-[(2S)-2-hexanamido-3-(4-hydroxyphenyl)propanamido]-3-methylpentanamido]hexanamide. It is stored at -20°C and has a purity of ≥98%.
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| Toxicity/Toxicokinetics |
The toxicity profile of dihexa is characterized in preclinical safety studies. As an HGF/c-Met pathway activator, the compound may affect cell growth and survival. The compound is for research use only and is not approved for clinical use. Appropriate safety precautions should be taken during handling.
|
| References |
[3]. Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells. Curr Protoc Stem Cell Biol. 2016 Aug 17;38:1G.6.1-1G.6.18. |
| Additional Infomation |
Dihexa (PNB-0408) is an orally active, blood-brain barrier-permeable analog of angiotensin IV that activates the hepatocyte growth factor (HGF)/c-Met system. It binds to HGF with a Kd of 65 pM and potentiates its activity at c-Met. Dihexa promotes synaptogenesis and is seven orders of magnitude more potent than BDNF in neurotrophic activity assays. It has potential for the study and treatment of neurodegenerative diseases.
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| Molecular Formula |
C27H44N4O5
|
|---|---|
| Molecular Weight |
504.662
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| Exact Mass |
504.331
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| CAS # |
1401708-83-5
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| PubChem CID |
129010512
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| Appearance |
Solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
866.2±65.0 °C at 760 mmHg
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| Flash Point |
477.6±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
|
| Index of Refraction |
1.529
|
| LogP |
2.78
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
36
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| Complexity |
679
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
CCCCCC(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCCCCCC(=O)N
|
| InChi Key |
XEUVNVNAVKZSPT-JTJYXVOQSA-N
|
| InChi Code |
InChI=1S/C27H44N4O5/c1-4-6-8-12-24(34)30-22(18-20-13-15-21(32)16-14-20)26(35)31-25(19(3)5-2)27(36)29-17-10-7-9-11-23(28)33/h13-16,19,22,25,32H,4-12,17-18H2,1-3H3,(H2,28,33)(H,29,36)(H,30,34)(H,31,35)/t19-,22-,25-/m0/s1
|
| Chemical Name |
(2S,3S)-N-(6-amino-6-oxohexyl)-2-[[(2S)-2-(hexanoylamino)-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanamide
|
| 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 |
| 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) |
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
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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 | 1.9815 mL | 9.9077 mL | 19.8153 mL | |
| 5 mM | 0.3963 mL | 1.9815 mL | 3.9631 mL | |
| 10 mM | 0.1982 mL | 0.9908 mL | 1.9815 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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