Canertinib (CI-1033)

Catalog No.S1019 Synonyms: PD183805

For research use only.

Canertinib (CI-1033, PD183805) is a pan-ErbB inhibitor for EGFR and ErbB2 with IC50 of 1.5 nM and 9.0 nM, no activity to PDGFR, FGFR, InsR, PKC, or CDK1/2/4. Phase 3.

Canertinib (CI-1033) Chemical Structure

CAS No. 267243-28-7

Selleck's Canertinib (CI-1033) has been cited by 43 publications

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Biological Activity

Description Canertinib (CI-1033, PD183805) is a pan-ErbB inhibitor for EGFR and ErbB2 with IC50 of 1.5 nM and 9.0 nM, no activity to PDGFR, FGFR, InsR, PKC, or CDK1/2/4. Phase 3.
Features First kinase inhibitor to show irreversible activity and to have entered clinical trials (serving as a template for further development).
Targets
EGFR [1]
(Cell-free assay)
ErbB2 [1]
(Cell-free assay)
1.5 nM 9.0 nM
In vitro

CI-1033 shows excellent potency for irreversible inhibition of erbB2 autophosphorylation in MDA-MB 453 cells. CI-1033 also shows high permeability in Caco-2 cells and inhibits secretory transport of vinblastine, which indicates that CI-1033 is a likely inhibitor of the P-gp. [1] CI-1033 alone, significantly suppresses constitutively activated Akt and MAP kinase. In combination with gemcitabine, CI-1033 inhibits Akt and prevents increased levels of MAPK phosphorylation. CI-1033 stimulates p27 expression and p38 phosphorylation in MDA-MB-453 cells. [2] CI-1033 is highly specific to the erbB receptor family and not sensitive to PGFR, FGFR or IR even at 50 μM. CI-1033 shows high levels of inhibition in A431 cells expressing EGFR with IC50 of 7.4 nM. CI-1033 suppresses heregulin-stimulated tyrosine phosphorylation of erbB2, erbB3 and erbB4 with IC50 of 5, 14 and 10 nM, respectively. CI-1033 also inhibits expression of pp62c-fos in response to heregulin. [3] CI-1033 is predicted to modify Cys773 covalently within the ATP binding site of the HER2 kinase and enhances destruction of both mature and immature ErbB-2 molecules. [4] CI-1033 induces a significant decrease in measurable phosphorylation of tyrosine residues 845 and 1068 of EGFR, which are responsible for Src and Ras/MAPK signaling respectively. The corresponding residues of Her-2, tyrosine residues 877 and 1248 are dephosphorylated significantly by CI-1033 at a concentration of 3 μM or higher. CI could block EGFR internalization and increase the rate of apoptosis in primary osteosarcoma cells in a titratable fashion. [5] In addition, CI-1033 inhibits the proliferation of TT, TE2, TE6 and TE10 cells significantly at 0.1 nM. [6]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human HCC827 cells NWDIOY1lWHKxbHnm[ZJifGmxbjDhd5NigQ>? MoTHO|IhcA>? M2WyUWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPDPFI4KGOnbHzzJIhiemKxcnnu[{BGT0[UIHTlcEBGPzR4LVG3OVAhdXW2YX70JIFnfGW{IEeyJIhzeyCkeTDNWHMh[XO|YYmsJGlEPTB;MD6wNFEh|ryP MlL3NlI{Ozl|NEK=
A431 cells NVLnUGlnTnWwY4Tpc44h[XO|YYm= MV;Jcohq[mm2aX;uJI9nKEWJRj3zeIlufWyjdHXkJIF2fG:yaH;zdIhwenmuYYTpc44hd2ZiRVfGVkBmdnq7bXWgbY4hSTR|MTDj[YxteyCmZYTlZ5Rm\CCkeTDpcY12dm:kbH;0eIlv\yxiSVO1NF0xNjByN{Sg{txO NH3wVHoyODd3M{S3OS=>
MDA-MB 453 cells MYfGeY5kfGmxbjDhd5NigQ>? Mn3RTY5pcWKrdHnvckBw\iCjdYTvdIhwe3Cqb4L5cIF1cW:wIH;mJGVTSkJ{IILlZ4VxfG:{IHvpcoF{\SCrbjDNSGEuVUJiNEWzJINmdGy|LDDJR|UxRTBwMEC5JO69VQ>? MV[xNFc2OzR5NR?=
human BT474 cells NIqxcYtRem:uaX\ldoF1cW:wIHHzd4F6 MljsN{Bl[Xm| NE\6[oJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFLUOFc1KGOnbHzzJI93\XKneIDy[ZN{cW6pIFXSRoIzKGGodHXyJFMh\GG7czDifUBu\XSqeXzlcoUh[my3ZTDzeIFqdmmwZzygSWM2OD1yLkCxJO69VQ>? M{XmfFE6ODJ6NEK0
mouse BAF3 cells NUi1NpNDTnWwY4Tpc44h[XO|YYm= NGTuRoJKdmirYnn0bY9vKG:oIFLsb{BmgHC{ZYPz[YQhcW5ibX;1d4UhSkGIMzDj[YxteyCjc4Pld5Nm\CCjczDjfZRwfG:6aXPpeJktKEmFNUC9NE4xOjlizszN NGqweYcyQDZ4N{OxNi=>
human HN5 cells M1TOcnBzd2yrZnXyZZRqd25iYYPzZZk> Ml;FN{Bl[Xm| MX;BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiQNTDj[YxteyCxdnXy[ZhxemW|c3nu[{BGT0[UIHHmeIVzKDNiZHH5d{BjgSCvZYTofYxmdmViYnz1[UB{fGGrbnnu[{whTUN3ME2wMlA2KM7:TR?= M4jwclE6ODJ6NEK0
human NCI-H1975 cells NFTLW5ZRem:uaX\ldoF1cW:wIHHzd4F6 MmHxO|IhcA>? NEL1b|dCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JOTl5NTDj[YxteyCqYYLic5JqdmdiRVfGVkBNQDV6Uj;UO|kxVSCvdYThcpQh[W[2ZYKgO|IhcHK|IHL5JG1VWyCjc4PhfUwhUUN3ME2wMlA3PCEQvF2= NGXDU2wzOjN|OUO0Ni=>
human A431 cells M3uzVnBzd2yrZnXyZZRqd25iYYPzZZk> NUD5XGlQPzJiaB?= M3HNd2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQUSzNUBk\WyuczDveoVz\XiycnXzd4lv\yCHR1\SJIFnfGW{IEeyJIhzeyCkeTDNWHMh[XO|YYmsJGlEPTB;MD6xOUDPxE1? NGqzWmQzOjN|OUO0Ni=>
human A549 cells M4XmfXBzd2yrZnXyZZRqd25iYYPzZZk> M2\1SVczKGh? MVLBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF3NEmgZ4VtdHNiZYjwdoV{e2mwZzD3bYxlKHS7cHWgSWdHWiClb3X4dJJme3Orbnegb{1T[XNibYX0ZY51KGGodHXyJFczKGi{czDifUBOXFNiYYPzZZktKEmFNUC9NU42QSEQvF2= M1nvOFIzOzN7M{Sy
mouse BAF3 cells MmLTSpVv[3Srb36gZZN{[Xl? M13ifWlvcGmkaYTpc44hd2ZiSlHLN{BmgHC{ZYPz[YQhcW5ibX;1d4UhSkGIMzDj[YxteyCjc4Pld5Nm\CCjczDjfZRwfG:6aXPpeJnwxIxiSVO1NF0zKM7:TR?= MmnFNVg3Pjd|MUK=
human HL7702 cells NWT3UnM3WHKxbHnm[ZJifGmxbjDhd5NigQ>? MYK3NkBp M13KcGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFy3O|AzKGOnbHzzJIV5eHKnc4Ppcochf2mudDD0fZBmKEWJRmKgZYZ1\XJiN{KgbJJ{KGK7IF3UV{Bie3OjeTygTWM2OD1{LkOg{txO NX3IcFhUOjJ|M{mzOFI>
human A431 cells NFvBdldHfW6ldHnvckBie3OjeR?= M{PJfFEh|ryP NGPY[JMyKGh? MUXJdpJmfmW{c3nicIUhcW6qaXLpeIlwdiCxZjDFS2ZTKGG3dH;wbI9{eGixconsZZRqd25iaX6gbJVu[W5iQUSzNUBk\WyuczDheEAyKHWPIHnuZ5Vj[XSnZDDmc5IhOSCqcjDmc4xtd3enZDDifUBkd22yb4Xu[EB4[XOqIH;1eEBu\WG|dYLl[EA2KGi{czDwc5N1KEWJRjDh[IRqfGmxbjDifUBY\XO2ZYLuJIJtd3S2aX7nJIFv[Wy7c3nz NHLLeYwzPDlyMEW5OC=>
human LNCaP cells NXXnenZUTnWwY4Tpc44h[XO|YYm= M1\ySlExKM7:TR?= NX\3W4d2OiCq M3LLVmlvcGmkaYTpc44hd2ZiYYX0c5Bpd3OyaH;yfYxifGmxbjDv[kBqdW23bn;wdoVkcXCrdHH0[YQh\myjZz30ZYdo\WRiQn34JIV5eHKnc4Pl[EBqdiCqdX3hckBNVkOjUDDj[YxteyCjc4Pld5Nm\CCjczDpcoNwenCxcnH0bY9vKG:oIGuzNnBeSVSSIHH0JFExKHWPIIDy[ZRz\WG2ZXSg[o9zKDJiaILzJIJm\m:{ZTD0doFve2[nY4Tpc44h[nliaX3teY5w[myxdDDhcoFtgXOrcx?= MWSxPFY3PzNzMh?=
NCI-H1975 cells MXjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MXS0PEBp M{nLb2lvcGmkaYTpc44hd2ZiRVfGVkBNQDV6Uj;UO|kxVSCvdYThcpQhcW5iaIXtZY4hVkOLLVixPVc2KGOnbHzzJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vKGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZk> MUKyOFkxODV7NB?=
Assay
Methods Test Index PMID
Growth inhibition assay Cell viability 28638122
Western blot p-FAK / FAK / p-AKT / AKT ; pEGFR / EGFR / p-HER2 / HER2 / p-HER3 / HER3 / MUC4 25686822
In vivo CI-1033 shows impressive activity against A431 xenografts in nude mice at 5 mg/kg of body weight. [1] CI-1033 (20 to 80 mg/kg/d) achieves a high degree of tumor regressions in H125 xenograft models. [3] Oral administration of CI-1033 causes a marked inhibition of growth in TT, TE6 and TE10 xenografts in nude mice, without animal death and <10% weight loss. [6]

Protocol (from reference)

Kinase Assay:[1]
  • Tyrosine Kinase Assays:

    Enzyme assays for determination of IC50 are performed in 96-well filter plates in a total volume of 0.1 mL, containing 20 mM Hepes, pH 7.4, 50 mM sodium vanadate, 40 mM magnesium chloride, 10 μM adenosine triphosphate (ATP) containing 0.5 mCi of [32P]ATP, 20 mg of polyglutamic acid/tyrosine, 10 ng of EGFR tyrosine kinase, and appropriate dilutions of CI-1033. All components except the ATP are added to the well and the plate is incubated with shaking for 10 min at 25 °C. The reaction is started by adding [32P]ATP, and the plate is incubated at 25 °C for another 10 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid (TCA). The plate is kept at 4 °C for at least 15 min to allow the substrate to precipitate. The wells are then washed five times with 0.2 mL of 10% TCA and 32P incorporation determined with a Wallac β plate counter.

Cell Research:[6]
  • Cell lines: TT, TE2, TE6 and TE10 cells
  • Concentrations: 0.1-5.0 nM
  • Incubation Time: 1, 3, 5 and 7 days
  • Method: Cells (1 × 104) are seeded in each well of a 24-well plastic culture plate and left overnight in DMEM or RPMI-1640 supplemented with 10% FBS. The next morning, the cells are treated with the indicated concentrations of CI-1033 (0.1-5.0 nM) for varying periods (1, 3, 5 and 7 days). After treatment, the cells are counted using a Coulter counter. The percent of cell proliferation is calculated by this formula: treatment cell number/control cell number × 100 for each time period.
Animal Research:[1]
  • Animal Models: A431 xenografts established in nude mice
  • Dosages: ~18 mg/kg
  • Administration: Administered orally

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% propylene glycol, 5% Tween 80, 65% D5W
For best results, use promptly after mixing.

10 mg/mL

Chemical Information

Molecular Weight 485.94
Formula

C24H25ClFN5O3

CAS No. 267243-28-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00050830 Completed Drug: CI 1033 Lung Neoplasms Pfizer January 2003 Phase 2
NCT00174356 Completed Drug: CI 1033|Drug: PACLITAXEL|Drug: CARBOPLATIN Carcinoma Non-Small Cell Lung Pfizer December 2002 Phase 1
NCT00051051 Completed Drug: CI-1033 Breast Neoplasms Pfizer December 2002 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
I would like to know which is the best option/solvent to dilute CI-1033 (Catalog No.S1019) for in vivo experiments. (I am treating mice at 30mg/mL of CI-1033.)

Answer:
The compound in the formulation recommended (30% Propylene glycol, 5% Tween 80, 65% D5W) on our product page at 30mg/ml is suspension. It’s fine for oral gavage.

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