| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
c-Kit <1 μM (IC50) c-kit D816V <1 μM (IC50)
Bezuclastinib targets the KIT (c-Kit) receptor tyrosine kinase, specifically mutant forms such as KIT D816V. This mutant is commonly found in systemic mastocytosis and other cancers. By binding to and inhibiting these specific c-Kit mutants, it blocks the signaling pathways that promote the proliferation of cells driven by these mutations. Its high selectivity is designed to target imatinib-resistant KIT mutations. |
|---|---|
| ln Vitro |
In vitro, Bezuclastinib has been shown to be a potent and highly selective inhibitor of KIT, particularly the D816V mutant. 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, Bezuclastinib has demonstrated potential in treating KIT-driven cancers. Upon oral administration, it binds to and inhibits specific c-Kit mutants, leading to an inhibition of tumor cell proliferation. It has been studied in clinical trials for advanced mastocytosis. Its development highlights its potential for treating imatinib-resistant KIT mutant cancers.
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| Enzyme Assay |
Cell-free assays for Bezuclastinib typically involve measuring its inhibitory activity against KIT kinases, including wild-type and mutant forms like D816V, using biochemical kinase assays. The compound's IC50 values are determined by measuring the phosphorylation of a peptide substrate in the presence of varying concentrations of the inhibitor. 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 Bezuclastinib. 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 Bezuclastinib effectively blocks KIT D816V-mediated signaling.
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| Animal Protocol |
In vivo animal experiments typically involve xenograft models of KIT-driven cancers, particularly those with the D816V mutation. Mice bearing these tumors are administered Bezuclastinib orally. Tumor growth is monitored over time to assess the compound's efficacy. These studies are essential for demonstrating the in vivo anti-tumor activity of the compound.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Bezuclastinib are characteristic of an orally bioavailable small molecule inhibitor. The compound is designed to have favorable drug-like properties to support oral administration and efficacy in vivo. While detailed PK parameters are not widely published, its oral bioavailability is a key feature for its clinical development.
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| Toxicity/Toxicokinetics |
The toxicity profile of Bezuclastinib is not extensively documented but is likely to be similar to other KIT inhibitors. Common adverse effects may include fatigue, edema, and gastrointestinal disturbances. In preclinical studies, Bezuclastinib has been shown to be well-tolerated, with a safety profile that supports its clinical development.
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| References |
[1]. Guoxian Wu, et al. Preparation of phenylpyrrolopyridinylheteroarylcarboxamide derivatives and analogs for use as c-kit protein kinases or mutant c-kit protein kinases modulators. Patent WO2014100620 A2.
[2]. WHO Drug Information, Vol. 35, No. 4, 2021. Geneva: World Health Organization; 2022. |
| Additional Infomation |
Bezuclastinib is an orally bioavailable protein tyrosine kinase inhibitor that inhibits mutated forms of the tumor-associated antigen mast cell/stem cell factor receptor c-Kit (SCFR), exhibiting potential antitumor activity. After oral administration, Bezuclastinib binds to specific c-Kit mutants and inhibits their activity. This may lead to suppression of tumor cell proliferation in cancer cell types that overexpress these c-Kit mutations. c-Kit is a transmembrane protein and receptor tyrosine kinase that is overexpressed in solid tumors and hematologic malignancies; it plays a crucial role in the regulation of cell differentiation and proliferation.
Drug Indications Treatment of gastrointestinal stromal tumors Bezuclastinib is a clinical-stage KIT inhibitor being developed for the treatment of advanced systemic mastocytosis and other KIT-driven cancers. Its high selectivity for the KIT D816V mutant and its ability to overcome imatinib resistance are key features. It represents a promising therapeutic strategy for patients with KIT mutant-driven diseases. |
| Molecular Formula |
C19H17N5O
|
|---|---|
| Molecular Weight |
331.371183156967
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| Exact Mass |
331.143
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| CAS # |
1616385-51-3
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| PubChem CID |
75593308
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| Appearance |
White to off-white solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
|
| Heavy Atom Count |
25
|
| Complexity |
480
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C(C)=C(C)NN=1)NC1=CN=C2C(=C1)C=C(C1C=CC=CC=1)N2
|
| InChi Key |
NVSHVYGIYPBTEZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17N5O/c1-11-12(2)23-24-17(11)19(25)21-15-8-14-9-16(22-18(14)20-10-15)13-6-4-3-5-7-13/h3-10H,1-2H3,(H,20,22)(H,21,25)(H,23,24)
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| Chemical Name |
4,5-dimethyl-N-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazole-3-carboxamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 80 mg/mL (241.42 mM)
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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 | 3.0178 mL | 15.0889 mL | 30.1777 mL | |
| 5 mM | 0.6036 mL | 3.0178 mL | 6.0355 mL | |
| 10 mM | 0.3018 mL | 1.5089 mL | 3.0178 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/NCT06915766
Conditions:Systemic Mastocytoses, Indolent|Systemic Mastocytoses, AggressiveLink: https://clinicaltrials.gov/ct2/show/NCT06948955
Conditions:Gastrointestinal Neoplasms, Gastrointestinal Stromal TumorsLink: https://clinicaltrials.gov/ct2/show/NCT04996875
Conditions:Advanced Systemic Mastocytosis (AdvSM)|SM With an Associated Hematologic Neoplasm (SM-AHN)|Mast Cell Leukemia (MCL)|Aggressive Systemic Mastocytosis (ASM)
Title:(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis
Status:Active, not recruiting
updateDate:2026-03-04
Ctid:NCT05186753
Link: https://clinicaltrials.gov/ct2/show/NCT05186753
Conditions:SSM|Mastocytosis, Indolent|Mastocytosis, Systemic|Mastocytosis|ISM|BMM|Smoldering Systemic Mastocytosis|Bone Marrow MastocytosisLink: https://clinicaltrials.gov/ct2/show/NCT05208047
Conditions:Advanced Gastrointestinal Stromal Tumors|Metastatic CancerLink: https://clinicaltrials.gov/ct2/show/NCT02401815
Conditions:Gastrointestinal Stromal TumorsProducts are for research use only; We do not sell to patients
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