| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| Other Sizes |
| Targets |
SHP2 (Src homology region 2 domain-containing phosphatase 2). It binds to wild-type SHP2 and the constitutively activating SHP2E76K mutant with Kd values of 49 and 211 nM, respectively. It is more selective for SHP2 than other phosphatases including SHP1.
|
|---|---|
| ln Vitro |
IACS-13909 (10 nM-10 μM; 14 days) treatment can successfully stop wild-type SHP2 and KYSE-520 cells from proliferating [1]. The growth of wild-type SHP2 and KYSE-520 cells is efficiently inhibited by IACS-13909 (1-5 μM; 2 hours) treatment [1]. In a dose-dependent manner, IACS-13909 similarly and efficaciously (GI50 ~1 μM) reduces the proliferation of parental cells and NCI-H1975 CS cells. KYSE-520 cells' pERK and pMEK values [1].
IACS-13909 has an IC50 of 15.7 nM and a Kd of 32 nM for SHP2. It decreases the levels of phosphorylated ERK in KYSE-520 esophageal squamous cell carcinoma cells with an IC50 of 47 nM. It inhibits human-ether-a-go-go (hERG) channels with an IC50 of 180 nM in whole-cell patch-clamp assays. |
| ln Vivo |
IACS-13909 (70 mg/kg; sidewall; daily; for 21 days tumor) administration revealed strong tumor growth suppression, with 100% tumor growth inhibition (TGI) reported after 21 days in the scaffold [1].
In an EGFR-overexpressing KYSE-520 mouse xenograft model, IACS-13909 decreases tumor volume without affecting body weight when administered at a dose of 70 mg/kg per day. This demonstrates its in vivo antitumor efficacy and a manageable safety profile. |
| Enzyme Assay |
In vitro enzyme assays typically use recombinant SHP2 protein and a surrogate substrate such as DiFMUP (6,8-difluoro-4-methylumbelliferyl phosphate). The compound is incubated with the enzyme and substrate, and the fluorescence signal is measured to calculate IC50 values. Binding affinity (Kd) is determined using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC).
|
| Cell Assay |
Cell Proliferation Assay [1]
Cell Types: Wild-type SHP2 and KYSE-520 Cell Tested Concentrations: 10 nM, 100 nM, 1. 0.041-3.3 μM) inhibits pERK in NCI-H1975 CS cells in a dose-coupled manner [1]. μM, 10 μM Incubation Duration: 14 days Experimental Results: Effectively inhibited cell proliferation. Western Blot Analysis[1] Cell Types: wild-type SHP2 and KYSE-520 Cell Tested Concentrations: 1 μM, 5 μM Incubation Duration: 2 hrs (hours) Experimental Results: Effectively inhibited pERK and pMEK levels. Cells (e.g., KYSE-520) are treated with various concentrations of IACS-13909 for a specified time. Cell viability is measured using CellTiter-Glo or MTT assays. Phosphorylated ERK levels are quantified by Western blotting or ELISA to assess pathway inhibition. In vivo studies are conducted in mouse xenograft models. IACS-13909 is formulated in a suitable vehicle and administered orally (e.g., 70 mg/kg per day). Tumor volume is measured using calipers, and body weight is monitored. Tumor tissues are collected for histopathological and biochemical analysis. |
| Animal Protocol |
Animal/Disease Models: NSG mice (20-28 g) were injected with KYSE-520 cells [1].
Doses: 70 mg/kg. Route of Administration: oral; daily; lasting for 21 days. Experimental Results: Effectively inhibited tumor growth in mice. IACS-13909 is orally active. It has a molecular weight of 377.27 and is sparingly soluble in DMSO and ethanol (1-10 mg/ml). Detailed pharmacokinetic parameters such as oral bioavailability, half-life, and clearance are available from specialized databases. It is recommended to store the compound at -20°C. |
| ADME/Pharmacokinetics |
In vivo studies in mouse xenograft models report no significant effect on body weight at the efficacious dose of 70 mg/kg per day. However, IACS-13909 inhibits hERG channels (IC50 = 180 nM), suggesting a potential risk for cardiac toxicity that requires further evaluation.
|
| Toxicity/Toxicokinetics |
IACS-13909 is a research-grade SHP2 allosteric inhibitor. It suppresses MAPK pathway signaling in RTK-dependent cancers. It is not approved for clinical use and is available for research purposes only. Its molecular formula is C17H18Cl2N6 and its molecular weight is 377.27.
|
| References |
| Molecular Formula |
C17H18CL2N6
|
|---|---|
| Molecular Weight |
377.271020412445
|
| Exact Mass |
376.1
|
| Elemental Analysis |
C, 54.12; H, 4.81; Cl, 18.79; N, 22.28
|
| CAS # |
2160546-07-4
|
| PubChem CID |
132166923
|
| Appearance |
White to yellow solid powder
|
| LogP |
3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
25
|
| Complexity |
472
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1(CCN(CC1)C2=NC3=NNC(=C3N=C2)C4=C(C(=CC=C4)Cl)Cl)N
|
| InChi Key |
AMADCPJVPLUGQO-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H18Cl2N6/c1-17(20)5-7-25(8-6-17)12-9-21-15-14(23-24-16(15)22-12)10-3-2-4-11(18)13(10)19/h2-4,9H,5-8,20H2,1H3,(H,22,23,24)
|
| Chemical Name |
1-[3-(2,3-dichlorophenyl)-2H-pyrazolo[3,4-b]pyrazin-6-yl]-4-methylpiperidin-4-amine
|
| Synonyms |
IACS-13909; IACS 13909; IACS13909; BBP-398; BBP 398; BBP398;
|
| 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 : ~10 mg/mL (~26.51 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.65 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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 | 2.6506 mL | 13.2531 mL | 26.5062 mL | |
| 5 mM | 0.5301 mL | 2.6506 mL | 5.3012 mL | |
| 10 mM | 0.2651 mL | 1.3253 mL | 2.6506 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
