| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
HG-7-86-01 targets mutant FLT3 (FMS-like tyrosine kinase 3) and Bcr-Abl tyrosine kinases, including the imatinib-resistant T315I gatekeeper mutant. As a type II tyrosine kinase inhibitor, HG-7-86-01 binds to the inactive DFG-out conformation of the kinase, stabilizing it in an inactive state. FLT3 is frequently mutated in acute myeloid leukemia (AML), while Bcr-Abl is the driver of chronic myeloid leukemia (CML).
|
|---|---|
| ln Vitro |
HG-7-86-01 shows potent in vitro activity as a type II tyrosine kinase inhibitor with validated intermediate potency (FLT3-ITD IC50 125-250 nM), enabling partial pathway inhibition and DFG-out conformational studies. The compound demonstrates defined potency across FLT3 mutants (ITD, Y572C, N841I, D835Y) and T315I Bcr-Abl. HG-7-86-01 shows synergy with PKC412 in ITD/Y572C models (CI < 0.7) and antagonism with N676D.
|
| ln Vivo |
In vivo activity of HG-7-86-01 has been demonstrated in preclinical models of drug-resistant leukemia. The compound's activity against both wild-type and the imatinib-resistant T315I gatekeeper mutant of Bcr-Abl positions it as a research-tool compound for interrogating type II kinase inhibition in drug-resistant leukemia models. However, detailed in vivo efficacy data have not been extensively reported in the available literature.
|
| Enzyme Assay |
Non-cell-based kinase assays for HG-7-86-01 typically involve measuring the inhibition of recombinant FLT3 or Bcr-Abl kinase activity using a radioactive or fluorescence-based assay. A standard protocol includes: incubating purified kinase with a peptide substrate and ATP in kinase buffer. HG-7-86-01 is added at various concentrations (0.001–100 μM), and the phosphorylation of the substrate is measured. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
Cellular assays for HG-7-86-01 typically involve leukemia cell lines driven by mutant FLT3 or Bcr-Abl, such as Ba/F3 cells expressing FLT3-ITD or T315I Bcr-Abl. A representative protocol includes: culturing cells in appropriate medium, treating with HG-7-86-01 at various concentrations (0.001–100 μM) for 48–72 hours, and assessing cell viability using MTT or CellTiter-Glo assays. To confirm on-target activity, phosphorylation of downstream substrates is measured by Western blot.
|
| Animal Protocol |
In vivo animal studies with HG-7-86-01 are conducted in xenograft mouse models of drug-resistant leukemia, such as Ba/F3-FLT3-ITD or Ba/F3-T315I Bcr-Abl xenografts. A typical protocol involves subcutaneous implantation of tumor cells in immunodeficient mice, allowing tumors to reach a certain size, administering HG-7-86-01 via oral gavage or intraperitoneal injection at doses determined from pharmacokinetic studies, monitoring tumor growth and body weight, and harvesting tumors for analysis of kinase inhibition and downstream signaling by Western blot.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of HG-7-86-01 have not been extensively reported in the available literature. The compound has a molecular weight of 562.6 g/mol and a molecular formula of C28H21F3N6O2S. HG-7-86-01 is soluble in DMSO and is typically stored as a powder at -20°C. Further PK studies are needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
|
| Toxicity/Toxicokinetics |
As a research compound, HG-7-86-01 is not intended for human therapeutic use, and comprehensive toxicological data are limited to preclinical studies. Standard safety assessments would include cytotoxicity screening, hERG channel inhibition testing, and preliminary toxicology studies in animal models to determine maximum tolerated dose and identify potential target organs of toxicity. The compound is for research use only.
|
| References | |
| Additional Infomation |
HG-7-86-01 (Compound 26, CAS 1258391-14-8) is a thiazolo[5,4-b]pyridine-based, ATP-competitive type II tyrosine kinase inhibitor developed through a hybrid-design strategy merging structural features of dasatinib and nilotinib. The compound potently inhibits the proliferation of cells driven by mutant FLT3 and displays cellular activity against both wild-type and the imatinib-resistant T315I gatekeeper mutant of Bcr-Abl. HG-7-86-01 is referenced in the primary literature (Molecular Cancer Therapeutics, 2010; Bioorganic & Medicinal Chemistry Letters, 2012).
|
| CAS # |
1258391-14-8
|
|---|---|
| Appearance |
White to off-white solid powder
|
| 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)
|
| Solubility (In Vitro) |
DMSO :~5 mg/mL (~8.89 mM; with sonication (<60°C))
|
|---|---|
| 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.) |
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
