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| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
SYR-127063 targets HER2 (human epidermal growth factor receptor 2), a member of the ErbB family of receptor tyrosine kinases. HER2 is a transmembrane protein that lacks a known ligand but can form heterodimers with other ErbB receptors (EGFR/HER1, HER3, HER4), leading to activation of downstream signaling pathways such as PI3K/AKT and MAPK/ERK that promote cell proliferation, survival, and differentiation. Overexpression or amplification of HER2 is observed in approximately 20-25% of breast cancers and is associated with aggressive disease and poor prognosis. SYR-127063 inhibits HER2 with high potency (IC50 = 11 nM) and shows selectivity over EGFR (IC50 = 429 nM) and HER4 (IC50 > 10000 nM). The compound binds to HER2 in an active-like conformation.
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| ln Vitro |
SYR-127063 demonstrates potent in vitro activity against HER2 with an IC50 of 11 nM. The compound shows significant selectivity for HER2 over EGFR (approximately 39-fold) and HER4 (>900-fold). This selectivity profile makes SYR-127063 a valuable tool for studying HER2-specific signaling pathways without significant off-target inhibition of other ErbB family members. The compound's ability to bind HER2 in an active-like conformation suggests that it may be a Type I inhibitor that binds to the ATP-binding site of the active kinase conformation. In cellular assays, SYR-127063 inhibits HER2 phosphorylation and downstream signaling in HER2-dependent cancer cell lines.
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| ln Vivo |
In vivo efficacy data for SYR-127063 are not extensively documented in publicly available sources. However, based on its potent and selective HER2 inhibitory activity, the compound is expected to have potential utility in HER2-driven cancer models. SYR-127063's selectivity for HER2 over EGFR and HER4 suggests that it may have an improved side effect profile compared to pan-ErbB inhibitors. The compound is a valuable tool for studying the role of HER2 in cancer and for evaluating HER2-targeted therapeutic strategies. Further in vivo studies in HER2-amplified tumor xenograft models would be needed to fully characterize the compound's antitumor efficacy and pharmacokinetic properties.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for SYR-127063 measures the inhibition of HER2 kinase activity. Recombinant human HER2 kinase domain is incubated with varying concentrations of SYR-127063 (typically ranging from nanomolar to micromolar) in the presence of ATP and a peptide substrate. The kinase reaction is allowed to proceed for a fixed period, and the extent of substrate phosphorylation is quantified using techniques such as fluorescence polarization, luminescence-based kinase assays, or radiometric measurement. IC50 values are determined by fitting dose-response curves to the inhibition data. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations, with DMSO concentration kept constant across all wells. Appropriate positive controls (known HER2 inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for SYR-127063 is performed using HER2-amplified cancer cell lines, such as BT-474 or SK-BR-3 breast cancer cells. Cells are cultured in appropriate medium and treated with varying concentrations of SYR-127063 (typically ranging from nanomolar to micromolar) or vehicle control (DMSO) for specified time points (e.g., 2-72 hours). The phosphorylation status of HER2 and downstream signaling proteins (e.g., AKT, ERK) is assessed by Western blotting using phospho-specific antibodies. Cell proliferation and viability are assessed using assays such as MTT, CellTiter-Glo, or by direct cell counting. Dose-response relationships are established by analyzing the inhibition of HER2 phosphorylation and cell viability across different compound concentrations.
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| Animal Protocol |
In vivo animal experiments with SYR-127063 are not extensively described in publicly available sources. Based on its in vitro activity against HER2, potential in vivo studies would likely use immunocompromised mice bearing HER2-amplified human breast cancer xenografts (e.g., BT-474 or SK-BR-3). Tumor-bearing mice would be randomized into treatment groups receiving SYR-127063 or vehicle control. SYR-127063 would be administered via oral gavage or intraperitoneal injection at various doses. Tumor volume would be measured twice weekly using calipers, and body weight monitored to assess tolerability. At study endpoint, tumors would be harvested for analysis of HER2 phosphorylation, downstream signaling, and markers of proliferation and apoptosis. The compound's antitumor efficacy would be evaluated by comparing tumor growth inhibition in treated versus control groups.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for SYR-127063 are not extensively documented in publicly available sources. As a small-molecule kinase inhibitor with a molecular weight of approximately 492.88, the compound is expected to have reasonable oral bioavailability. SYR-127063 has a chemical formula of C23H20ClF3N4O3. The compound is soluble in DMSO for formulation purposes. For in vivo administration, the compound would need to be formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored at -20°C for long-term stability. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are not available from the current search results and would require consultation of the primary literature.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for SYR-127063 are not extensively documented in publicly available sources. As a research-grade compound, SYR-127063 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References |
:J Biol Chem. 2011 May 27;286(21):18756-65.
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| Additional Infomation |
SYR-127063 is a research compound developed for studying the role of HER2 in cancer and for evaluating HER2-targeted therapeutic strategies. The compound is a potent and selective HER2 inhibitor with an IC50 of 11 nM, showing significant selectivity over EGFR (429 nM) and HER4 (>10000 nM). SYR-127063 binds to HER2 in an active-like conformation. The compound is also known as BDBM92454. SYR-127063 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical cancer research. The compound is available from various chemical suppliers for research purposes. Its utility lies in its ability to selectively inhibit HER2 with high potency, making it a valuable tool for dissecting HER2-driven signaling pathways.
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| Molecular Formula |
C23H20CLF3N4O3
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| Molecular Weight |
492.8781
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| Exact Mass |
492.117
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| CAS # |
871026-18-5
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| PubChem CID |
11684629
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
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| Complexity |
635
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)OC2=C(C=C(C=C2)NC3=NC=NC4=C3N(C=C4)CCOCCO)Cl)C(F)(F)F
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| InChi Key |
CMMUJJHJYMYOJR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H20ClF3N4O3/c24-18-13-16(4-5-20(18)34-17-3-1-2-15(12-17)23(25,26)27)30-22-21-19(28-14-29-22)6-7-31(21)8-10-33-11-9-32/h1-7,12-14,32H,8-11H2,(H,28,29,30)
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| Chemical Name |
2-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy)ethan-1-ol
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| Synonyms |
SYR127063; SYR-127063; SYR 127063; BDBM92454; BDBM-92454; BDBM 92454.
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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) |
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
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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 | 2.0289 mL | 10.1445 mL | 20.2889 mL | |
| 5 mM | 0.4058 mL | 2.0289 mL | 4.0578 mL | |
| 10 mM | 0.2029 mL | 1.0144 mL | 2.0289 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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