| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SHP2 (PTPN11). IACS-15414 is an allosteric SHP2 inhibitor that binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, stabilizing the autoinhibited conformation and preventing SHP2 activation, thereby blocking downstream RAS-MAPK signaling.
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| ln Vitro |
IACS-15414 is a potent SHP2 inhibitor with an IC50 of 122 nM. It is orally bioavailable and demonstrates significant biological activity by modulating signaling pathways associated with cancer cell proliferation and survival. In cellular assays, IACS-15414 reduces pERK levels and inhibits proliferation of cancer cell lines that are dependent on SHP2 signaling, including those with KRAS mutations, RTK alterations, and NF1 loss.
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| ln Vivo |
No specific in vivo efficacy data are reported. As a potent and orally bioavailable SHP2 inhibitor, IACS-15414 is expected to demonstrate antitumor activity in mouse xenograft models of SHP2-dependent cancers. It likely represents a clinical candidate or lead compound, but detailed efficacy studies have not been published. The compound is used in cancer research.
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| Enzyme Assay |
Cell-free SHP2 phosphatase activity assays are performed using recombinant SHP2 enzyme and a bis-phosphorylated IRS-1 peptide substrate. The enzyme is incubated with increasing concentrations of IACS-15414 (0.01-10,000 nM) in assay buffer (50 mM HEPES, pH 7.2, 100 mM NaCl, 5 mM DTT, 2 mM EDTA) for 30-60 min at 25degC. The reaction is quenched, and IC50 (122 nM) is determined by measuring released phosphate using a malachite green phosphate detection kit or by using a fluorescent substrate. Selectivity is assessed against other phosphatases (e.g., SHP1, PTP1B).
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| Cell Assay |
Human cancer cell lines with SHP2-dependent signaling (e.g., KYSE520 esophageal cancer, NCI-H441 lung cancer, or KRAS-mutant cell lines) are seeded and treated with IACS-15414 at various concentrations (0.1-10 uM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. pERK levels (downstream of RAS-MAPK) are measured by Western blot or phospho-flow cytometry. Apoptosis is measured by Annexin V/PI staining and flow cytometry. Colony formation assays are performed over 7-14 days. IC50 values for growth inhibition are determined.
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| Animal Protocol |
No specific in vivo animal protocols are published for IACS-15414. For potential in vivo studies, IACS-15414 would be administered orally to mice bearing tumor xenografts of SHP2-dependent cancer cell lines. Dosing regimens would likely include once or twice daily administration at doses ranging from 10-100 mg/kg. Tumor volumes would be measured with calipers. At study termination, tumors would be excised for pERK measurement by Western blot or immunohistochemistry to confirm target engagement. No such studies are reported.
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| ADME/Pharmacokinetics |
No specific PK data are reported for IACS-15414. The molecular weight is 423.34 (C20H24Cl2N4O2). CAS 2411321-29-2. Formula: C20H24Cl2N4O2. IUPAC name: 6-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(2,3-dichlorophenyl)-2-methylpyrimidin-4(3H)-one. The compound is described as orally bioavailable. Solubility: DMSO (10-50 mg/mL). Storage: -20degC. PK parameters (t1/2, Cmax, AUC) have not been characterized.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for IACS-15414. As an allosteric SHP2 inhibitor, its safety profile is expected to be manageable, but comprehensive toxicological assessments have not been published. No clinical trials have been conducted. The compound is not FDA-approved. For research use only.
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| References | |
| Additional Infomation |
Other information: IACS-15414 (CAS 2411321-29-2) is a research compound, not FDA-approved. It is a potent and orally bioavailable allosteric SHP2 inhibitor with an IC50 of 122 nM. It is used in cancer research to study SHP2-dependent signaling pathways, particularly in KRAS-mutant and RTK-driven cancers. Purity ≥98%. For research use only. Synonyms: IACS15414, IACS 15414.
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| Molecular Formula |
C20H24CL2N4O2
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|---|---|
| Molecular Weight |
423.336162567139
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| Exact Mass |
422.127
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| CAS # |
2411321-29-2
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| PubChem CID |
146364381
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| Appearance |
White to light yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
28
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| Complexity |
690
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1(C)=NC(N2CCC3(CO[C@@H](C)[C@H]3N)CC2)=CC(=O)N1C1=CC=CC(Cl)=C1Cl
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| InChi Key |
WYUIJDCKOPRFJO-HXPMCKFVSA-N
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| InChi Code |
InChI=1S/C20H24Cl2N4O2/c1-12-19(23)20(11-28-12)6-8-25(9-7-20)16-10-17(27)26(13(2)24-16)15-5-3-4-14(21)18(15)22/h3-5,10,12,19H,6-9,11,23H2,1-2H3/t12-,19+/m0/s1
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| Chemical Name |
6-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methylpyrimidin-4-one
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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: ~100 mg/mL (~236.2 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.91 mM) 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; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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. Solubility in Formulation 2: 2.5 mg/mL (5.91 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 2.3622 mL | 11.8108 mL | 23.6217 mL | |
| 5 mM | 0.4724 mL | 2.3622 mL | 4.7243 mL | |
| 10 mM | 0.2362 mL | 1.1811 mL | 2.3622 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.
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