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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
PKI166 targets the epidermal growth factor receptor (EGFR) family, specifically HER1 (EGFR) and HER2 (ErbB2) tyrosine kinases. It acts as a reversible, ATP-competitive inhibitor. The compound has a reported IC₅₀ of 0.7 nM against the EGFR kinase domain. By inhibiting EGFR and HER2 tyrosine kinase activity, PKI166 blocks downstream signaling pathways involved in tumor cell proliferation and survival.
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| ln Vitro |
In human pancreatic cancer cells, pretreatment with PKI-166 (0-0.5 μM; 1 hour) suppresses EGFR autophosphorylation [1]. PKI-166 (0.03 μM; 6 days) amplifies the cytotoxicity of gemcitabine [1].
In vitro, PKI166 (PKI-166) is a potent inhibitor of EGFR tyrosine kinase with an IC₅₀ of 0.7 nM against the EGFR kinase domain. It reversibly inhibits HER1 and HER2 tyrosine kinases. The compound exhibits anti-tumor activity in various cancer cell lines. Detailed in vitro activity data is available in the primary literature. |
| ln Vivo |
Pancreatic cancer growth is inhibited by PKI-166 (100 mg/kg; oral; daily; days 7 to 35 following xenotransplantation) [1].
In vivo, PKI166 has anti-tumor activity and inhibits tumor growth and metastasis. The compound is orally bioavailable. It has been studied in preclinical tumor models. Specific efficacy data and dosing regimens are described in the primary literature. |
| Enzyme Assay |
Non-cellular enzyme assays for PKI166 involve measuring EGFR tyrosine kinase inhibition. The kinase is incubated with ATP, substrate, and varying concentrations of PKI166. Phosphorylation of the substrate is measured using radioactive or luminescent methods. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: L3.6pl Cell Tested Concentrations: 0.01 μM, 0.05 μM, 0.5 μM Incubation Duration: 1 hour Experimental Results: Inhibition of EGFR autophosphorylation in a dose-dependent manner. Cytotoxicity assay[1] Cell Types: L3.6pl Cell Tested Concentrations: 0.03 μM Incubation Duration: 6 days Experimental Results: Enhanced gemcitabine-mediated cytotoxicity. In vitro cellular experiments involve treating cancer cell lines expressing EGFR or HER2 with PKI166 at various concentrations. Cell proliferation is measured using standard assays. EGFR and HER2 phosphorylation is assessed by Western blot to confirm target inhibition. Downstream signaling pathways such as MAPK and PI3K/AKT are also analyzed. |
| Animal Protocol |
Animal/Disease Models: L3.6pl cell xenograft male athymic nude mice (8-12 weeks) [1]
Doses: 100 mg/kg Route of Administration: Oral; Route of Administration: Oral. Routine; Results from days 7 to 35 after xenografting: Median tumor volume diminished Dramatically. In vivo animal studies involve tumor xenograft models in mice. PKI166 is administered orally. Tumor volume is measured over time to assess antitumor efficacy. Pharmacodynamic markers such as EGFR phosphorylation in tumor tissues are measured to confirm target engagement. |
| ADME/Pharmacokinetics |
PKI166 is orally bioavailable. It has a molecular weight of 330.38 g/mol and a molecular formula of C₂₀H₁₈N₄O. The compound is soluble in DMSO. Storage: powder at -20°C.
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| Toxicity/Toxicokinetics |
Specific toxicity data for PKI166 is limited. As an EGFR tyrosine kinase inhibitor, it would be expected to have on-target effects related to EGFR inhibition. The compound is for research purposes only and should be handled with appropriate safety precautions.
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| References | |
| Additional Infomation |
PKI-166, an EGFR/HER1/HER2 inhibitor, is a pyrrolopyrimidine epidermal growth factor receptor (EGFR) protein kinase inhibitor with anti-tumor activity. PKI-166 reversibly inhibits HER1 and HER2 tyrosine kinases (belonging to the epidermal growth factor receptor family), thereby inhibiting tumor growth and metastasis.
PKI166 (PKI-166, CGP-75166) is a potent, orally bioavailable, ATP-competitive inhibitor of EGFR tyrosine kinase with an IC₅₀ of 0.7 nM. It reversibly inhibits HER1 and HER2 tyrosine kinases and exhibits anti-tumor activity. This product is for research purposes only and is not for human therapeutic use. |
| Molecular Formula |
C20H18N4O
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|---|---|
| Molecular Weight |
330.39
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| Exact Mass |
330.148
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| CAS # |
187724-61-4
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| Related CAS # |
PKI-166 hydrochloride;2230253-82-2
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| PubChem CID |
6918403
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.576
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
420
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](C1=CC=CC=C1)NC2=NC=NC3=C2C=C(N3)C4=CC=C(C=C4)O
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| InChi Key |
XRYJULCDUUATMC-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C20H18N4O/c1-13(14-5-3-2-4-6-14)23-19-17-11-18(24-20(17)22-12-21-19)15-7-9-16(25)10-8-15/h2-13,25H,1H3,(H2,21,22,23,24)/t13-/m1/s1
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| Chemical Name |
4-[4-[[(1R)-1-phenylethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenol
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| Synonyms |
PKI-166; PKI 166; PKI166
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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 : ≥ 125 mg/mL (~378.35 mM)
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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 | 3.0267 mL | 15.1336 mL | 30.2673 mL | |
| 5 mM | 0.6053 mL | 3.0267 mL | 6.0535 mL | |
| 10 mM | 0.3027 mL | 1.5134 mL | 3.0267 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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