| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
PPY-A targets both the wild-type and the T315I mutant form of the Abelson tyrosine kinase (Abl). The T315I mutation, where threonine is replaced by isoleucine at the gatekeeper position, is a common cause of resistance to imatinib, dasatinib, and nilotinib. PPY-A overcomes this resistance through a unique binding mode; unlike other inhibitors, it does not occupy the hydrophobic pocket behind the gatekeeper residue. Instead, its binding relies on augmented contacts with the glycine-rich loop, which is critical for its ability to inhibit the T315I mutant.
|
|---|---|
| ln Vitro |
PPY-A is a potent inhibitor of both wild-type and T315I mutant Abl kinases in cell-free biochemical assays. It demonstrates IC50 values of 9 nM against the wild-type Abl and 20 nM against the T315I mutant. This high potency is a key feature of its activity profile. The compound's efficacy is measured by its ability to inhibit kinase activity, which is typically assessed using homogeneous time-resolved fluorescence resonance energy transfer (TR-FRET) assays.
|
| ln Vivo |
PPY-A exhibits potent anti-proliferative activity against Ba/F3 cells that are transformed with either wild-type Bcr-Abl or the T315I mutant Bcr-Abl gene. It inhibits the growth of these cells with IC50 values of 390 nM for the wild-type and 180 nM for the T315I mutant, respectively. This demonstrates its efficacy in a cellular context relevant to CML, a disease driven by the Bcr-Abl fusion protein.
|
| Enzyme Assay |
The primary non-cellular assay used to characterize PPY-A's activity is a homogeneous time-resolved fluorescence resonance energy transfer (TR-FRET) assay. In this assay, the inhibition of wild-type and T315I mutant Abl kinase activity is measured. The assay involves incubating the kinase enzyme with a substrate and varying concentrations of PPY-A. The TR-FRET signal, which is proportional to the phosphorylation of the substrate, is then measured to determine the compound's IC50 value.
|
| Cell Assay |
In vitro cellular activity is assessed using Ba/F3 cells, a murine pro-B cell line, that are genetically transformed to express either wild-type Bcr-Abl or the T315I mutant Bcr-Abl. These cells are treated with a range of PPY-A concentrations, and cell viability or proliferation is measured after a defined period, typically using an assay like MTT or CellTiter-Glo. The IC50, the concentration required to inhibit cell growth by 50%, is then calculated to determine the compound's cellular potency.
|
| Animal Protocol |
In vivo animal studies for PPY-A are not extensively detailed in standard product descriptions. However, based on its mechanism as a Bcr-Abl inhibitor, in vivo efficacy would typically be evaluated in mouse xenograft models using Ba/F3 cells transformed with Bcr-Abl (wild-type or T315I mutant). Tumor-bearing mice would be administered PPY-A via an appropriate route (e.g., oral or intraperitoneal), and tumor growth inhibition would be monitored as the primary efficacy endpoint.
|
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of PPY-A are not extensively characterized in the available literature. As a small molecule with a molecular weight of 372.42 and a LogP of 4.002, it is expected to have moderate to high lipophilicity. It is soluble in DMSO. For in vivo administration, it may be formulated in a vehicle like 10% DMSO, 5% Tween 80, and 85% saline. Specific parameters such as half-life, bioavailability, and volume of distribution are not documented.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for PPY-A are not available in the provided literature. As a research compound, it is not intended for human use and comprehensive toxicity studies are not typically conducted or published. Standard laboratory safety precautions should be observed when handling this compound. Its safety profile is only known within the context of its use in controlled in vitro and in vivo research settings.
|
| References | |
| Additional Infomation |
PPY-A is a research-grade compound for laboratory use only and is not approved for clinical use. Its primary application is in chronic myeloid leukemia (CML) research, particularly for studying the mechanisms of resistance to Abl kinase inhibitors and for developing strategies to overcome the T315I mutation. A key piece of information is the crystal structure of the T315I mutant of Abl kinase bound to PPY-A (PDB ID: 2Z60), which provides detailed insight into its unique binding mode.
|
| Molecular Formula |
C22H20N4O2
|
|---|---|
| Molecular Weight |
372.4198
|
| Exact Mass |
372.159
|
| CAS # |
875634-01-8
|
| PubChem CID |
16750094
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.002
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
28
|
| Complexity |
543
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(N(C)C)C1C=C(C2C=C3C(NC=C3C3C(OC)=CC=CC=3)=NC=2)C=NC=1
|
| InChi Key |
GYQRHHQPEMOLKH-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H20N4O2/c1-26(2)22(27)16-8-14(10-23-11-16)15-9-18-19(13-25-21(18)24-12-15)17-6-4-5-7-20(17)28-3/h4-13H,1-3H3,(H,24,25)
|
| Chemical Name |
5-[3-(2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethylpyridine-3-carboxamide
|
| 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) |
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
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 | 2.6851 mL | 13.4257 mL | 26.8514 mL | |
| 5 mM | 0.5370 mL | 2.6851 mL | 5.3703 mL | |
| 10 mM | 0.2685 mL | 1.3426 mL | 2.6851 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
