| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
IC50: 0.2 nM (KIT D816V)[2]
Elenestinib specifically targets the KIT D816V mutant. This mutation results in constitutive activation of the KIT receptor tyrosine kinase and is the primary driver of systemic mastocytosis. By selectively inhibiting KIT D816V with an IC50 of 6 nM, Elenestinib blocks the signaling pathways that drive the proliferation of mast cells in this disorder. Its selectivity for the mutant form is a key feature. |
|---|---|
| ln Vitro |
In vitro, Elenestinib has been shown to be a potent inhibitor of KIT D816V with an IC50 of 6 nM. Its activity is assessed using biochemical kinase assays that measure the phosphorylation of a substrate in the presence of the compound. Cell-based assays in KIT D816V-driven cell lines are used to confirm its anti-proliferative effects.
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| ln Vivo |
In vivo, Elenestinib is an orally active compound that has demonstrated potential for the research of systemic mastocytosis (SM). By inhibiting KIT D816V, it blocks signaling to inhibit the proliferation of cells driven by this mutation. Its minimal blood-brain barrier penetration may be advantageous by reducing CNS-related side effects.
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| Enzyme Assay |
Cell-free assays for Elenestinib typically involve measuring its inhibitory activity against KIT D816V using a biochemical kinase assay. The IC50 value of 6 nM is determined by measuring the phosphorylation of a peptide substrate in the presence of varying concentrations of the inhibitor. Selectivity is assessed by comparing the compound's potency against wild-type KIT and other kinases. These assays are used to characterize the compound's potency and selectivity.
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| Cell Assay |
In vitro cellular assays are conducted to evaluate the functional activity of Elenestinib. KIT D816V-driven cell lines are treated with the compound. Cell viability and proliferation are measured to assess anti-proliferative effects. KIT phosphorylation is measured to confirm inhibition of the target kinase. These assays confirm that Elenestinib effectively blocks KIT D816V-mediated signaling.
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| Animal Protocol |
In vivo animal experiments typically involve models of systemic mastocytosis or other KIT D816V-driven diseases. Animals are administered Elenestinib orally. Disease progression, mast cell populations, and other relevant biomarkers are monitored to assess the compound's efficacy. These studies are essential for demonstrating the in vivo activity of the compound.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Elenestinib are characterized by its oral activity and minimal blood-brain barrier penetration. Its molecular weight is 528.58. The compound is designed to have favorable drug-like properties to support oral administration and efficacy in vivo. Its minimal CNS penetration may be a safety advantage.
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| Toxicity/Toxicokinetics |
The toxicity profile of Elenestinib is not extensively documented but is likely to be similar to other KIT inhibitors. Its minimal blood-brain barrier penetration may reduce the risk of CNS-related side effects. In preclinical studies, Elenestinib has been shown to be well-tolerated, with a safety profile that supports its clinical development.
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| References |
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| Additional Infomation |
Elenestinib is a selective KIT inhibitor. Elenestinib is an orally bioavailable protein tyrosine kinase inhibitor that inhibits the D816V mutant of the tumor-associated antigen (TAA) mast cell/stem cell factor receptor (SCFR), exhibiting potential antitumor activity. After oral administration, Elenestinib binds to and inhibits the specific c-Kit mutant D816V. This may lead to the suppression of mast cell proliferation in patients overexpressing this c-Kit mutation. The D816V mutation refers to the substitution of valine for asparagine at position 816 of the mast cell/stem cell growth factor receptor Kit protein; this mutation may lead to mastocytosis and other mast cell disorders.
Elenestinib is a clinical-stage KIT D816V inhibitor being developed for the treatment of systemic mastocytosis (SM). Its potent activity (IC50 = 6 nM) and oral bioavailability make it a promising therapeutic candidate for this disease. Its minimal blood-brain barrier penetration is a notable feature that may differentiate it from other KIT inhibitors. |
| Molecular Formula |
C27H29FN10O
|
|---|---|
| Molecular Weight |
528.583966970444
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| Exact Mass |
528.25
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| CAS # |
2505078-08-8
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| Related CAS # |
Elenestinib phosphate;2832013-93-9
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| PubChem CID |
155190269
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| Appearance |
White to off-white solid powder
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| LogP |
1.1
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
39
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| Complexity |
789
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1C=CC(=CC=1)[C@@](C)(C1C=NC(=NC=1)N1CCN(C2C3=CC(C4C=NN(CCO)C=4)=CN3N=CN=2)CC1)N
|
| InChi Key |
IPMARPMXSFFZFG-MHZLTWQESA-N
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| InChi Code |
InChI=1S/C27H29FN10O/c1-27(29,21-2-4-23(28)5-3-21)22-14-30-26(31-15-22)36-8-6-35(7-9-36)25-24-12-19(17-38(24)34-18-32-25)20-13-33-37(16-20)10-11-39/h2-5,12-18,39H,6-11,29H2,1H3/t27-/m0/s1
|
| Chemical Name |
2-[4-[4-[4-[5-[(1S)-1-amino-1-(4-fluorophenyl)ethyl]pyrimidin-2-yl]piperazin-1-yl]pyrrolo[2,1-f][1,2,4]triazin-6-yl]pyrazol-1-yl]ethanol
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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 |
| 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) |
DMSO: 125 mg/mL (236.48 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (11.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 62.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8919 mL | 9.4593 mL | 18.9186 mL | |
| 5 mM | 0.3784 mL | 1.8919 mL | 3.7837 mL | |
| 10 mM | 0.1892 mL | 0.9459 mL | 1.8919 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.
Link: https://clinicaltrials.gov/ct2/show/NCT07388511
Conditions:Healthy ParticipantsLink: https://clinicaltrials.gov/ct2/show/NCT04910685
Conditions:Indolent Systemic Mastocytosis|Smoldering Systemic MastocytosisLink: https://clinicaltrials.gov/ct2/show/NCT05609942
Conditions:Advanced Systemic MastocytosisProducts are for research use only; We do not sell to patients
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