Gefitinib (ZD1839)

For research use only.

Catalog No.S1025 Synonyms: Iressa

499 publications

Gefitinib (ZD1839) Chemical Structure

CAS No. 184475-35-2

Gefitinib (ZD-1839, Iressa) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.

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Selleck's Gefitinib (ZD1839) has been cited by 499 publications

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Choose Selective EGFR Inhibitors

Biological Activity

Description Gefitinib (ZD-1839, Iressa) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.
Features A potent EGFR tyrosine kinase inhibitor.
Targets
Tyr1173 (NR6W cells) [1] Tyr1173 (NR6wtEGFR cells) [1] Tyr992 (NR6wtEGFR cells) [1] Tyr992 (NR6W cells) [1]
26 nM 37 nM 37 nM 57 nM
In vitro

Gefitinib effectively inhibits all tyrosine phosphorylation sites on EGFR in both the high and low-EGFR-expressing cell lines including NR6, NR6M and NR6W cell lines. The phosphorylation sites Tyr1173 and Tyr992 are less sensitive requiring higher concentrations of Gefitinib for inhibition. Gefitinib effectively blocks the phosphorylation of PLC-γ, with IC50 of 27nM, in NR6W cells. The NR6wtEGFR and NR6M cell lines has low levels of PLC-γ phosphorylation but the level in the NR6M cell line is more resistant to inhibition by Gefitinib with IC50 of 43 nM and 369 nM, respectively. Gefitinib inhibits Akt phosphorylations, with IC50 of 220 and 263nM, in the low-EGFR- and -EGFRvIII-expressing cell lines, respectively. Gefitinib in the dose range from 0.1 to 0.5μM significantly facilitates, rather than abrogates, colony formation of NR6M cells. However, at a concentration of 2 μM Gefitinib completely blocks NR6M colony formation. Gefitinib rapidly and in a dose-dependent manner inhibits EGFR and ERK phosphorylation up to 72 hours after EGF stimulation in both the high- and low-EGFR-expressing cell lines. [1] Gefitinib is the monolayer growth of these EGF-driven untransformed MCF10A cells with an IC50 of 20 nM. [2] The combination of Gefitinib (0.2 μM and 0.5 μM) with irradiation lead to a significant growth inhibition in LoVo cells, compared with radiation alone.. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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HT NUXGbYU1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkjBTWM2OD1{MT60N|MyKM7:TR?= M4T2c|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
HUTU-80 NYi3N4ZqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV\JR|UxRTJzLkSzN|Yh|ryP MmTrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
PA-1 M{XPOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnwTWM2OD1{MT6yO|g4KM7:TR?= MnrPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
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SW872 Mnv4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2faPGlEPTB;NECuNlA{OSEQvF2= NHPJRnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[zNVM2QSd-MkS2N|E{PTl:L3G+
HT-1197 NEfFfolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTJTWM2OD12MD6yPFY6KM7:TR?= M1vWflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5M{S5N|MzLz5{N{O0PVM{OjxxYU6=
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SNU-387 MlK0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;F[GFDUUN3ME20NE45OjN6IN88US=> NWnUSlhLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUe0NVk3ODRpPkG3OFE6PjB2PD;hQi=>
T47D NWDxcoJtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTRzLkCxPVIh|ryP MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDF6Nk[wOEc,OThzOE[2NFQ9N2F-
G-402 NHnIe|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYiwNlZGUUN3ME20NU4xQDB7IN88US=> M3zXWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NEi5OlI3Lz5{M{S4PVYzPjxxYU6=
MZ1-PC MlLTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXz5TmRSUUN3ME20NU45OSEQvF2= M3zuXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5NkCyOFY1Lz5zN{[wNlQ3PDxxYU6=
SW1417 Ml23S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;6dZo4UUN3ME20Nk4{ODNizszN MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzZyMkS2OEc,OTd4MEK0OlQ9N2F-
RERF-LC-MS Ml2wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjPTWM2OD12Mj61NFg4KM7:TR?= M37BblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NUe2OlM{Lz5{OEW3OlY{OzxxYU6=
SF539 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkjuTWM2OD12Mj61OVI6KM7:TR?= MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR6OU[yOkc,OjN2OEm2NlY9N2F-
ESS-1 M4nhNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTR|LkW1OVgh|ryP Mkm5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh3N{[2N|MoRjJ6NUe2OlM{RC:jPh?=
RO82-W-1 MkP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX;JR|UxRTR|Lk[xOVMh|ryP NIPoOVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEW3OlY{Oyd-Mki1O|Y3OzN:L3G+
S-117 MnjCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2fPXmlEPTB;NEOuOlk2QCEQvF2= MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjVzMkmwPEc,OjJ3MUK5NFg9N2F-
SW756 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTR|LkiyOFIh|ryP MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly5N|kwLz6VQV7HSXI9N2F-
CP66-MEL NWLMWWs1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPpTWM2OD12NT63NVQ{KM7:TR?= M2q2d|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
H-EMC-SS Mo\lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzaN41YUUN3ME20OU44Pjl|IN88US=> NIDoO4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw6OzlxJ{7TRW5ITVJ:L3G+
NCI-H2052 NVrQSJpTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHGR3AxUUN3ME20OU46ODJ5IN88US=> MlvtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
SW684 NF2ycnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTR5LkCwPFEh|ryP MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly5N|kwLz6VQV7HSXI9N2F-
HCC1569 MkfSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{DLOGlEPTB;NEeuNVY2QCEQvF2= Mne4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
KGN NETJN|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvqTYRLUUN3ME20O{4{OzFzIN88US=> M{n0bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
LCLC-103H MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH\iNGlKSzVyPUS3MlQ1ODRizszN M{\JflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
SW780 NYTyfYxmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jS[2lEPTB;NEeuOlM2OSEQvF2= MkDsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
NCI-H1703 MlLRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrtTmdpUUN3ME20PE4{OzV{IN88US=> NFLGcFI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw6OzlxJ{7TRW5ITVJ:L3G+
HCC1395 MlO3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTR6Lke0N|Ih|ryP MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly5N|kwLz6VQV7HSXI9N2F-

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
phospho-EGFR / phospho-ERK / phospho-SRC / phospho-AKT; 

PubMed: 22586683     


Effect of overexpressing CRKL on phosphorylation levels of EGFR, ERK, AKT and SRC in response to gefitinib. HCC827 cells expressing a control vector or CRKL were exposed to gefitinib at indicated concentrations for 6 h and cell lysates were collected for immunoblotting with indicated specific antibodies.

Cyclin D1/ p16 / p27 / pRb; 

PubMed: 18559346     


levels of phosphorylated and total EGFR, IGF-1R, Akt, ERK1/2, and Rb and levels of cyclin D1, p27, p16, and actin following 6- or 16-h treatment of A431 cells with combinations of 1 or 3 μm gefitinib and 3 μm NVP-ADW742. Data are representative of two independent experiments.

uc-caspase-9 / c-caspase-9 / uc-caspase-3 / c-caspase-3 / uc-PARP / PARP; 

PubMed: 23102728     


Apoptosis resulting from combined treatment with gefitinib and an MEK inhibitor. (A) apoptosis relating protein induced by gefitinib and/or AZD6244 in PC‐9/wt and PC‐9/gef B4 cells. (B) Apoptosis relating protein induced by gefitinib and/or CI‐1040 in PC‐9/wt and PC‐9/gef B4 cells. (C) apoptosis relating protein induced by gefitinib and/or AZD6244 in PC‐9/gefE3 and PC‐9/gefE7 cells. (D) apoptosis relating protein induced by gefitinib and/or CI‐1040 in PC‐9/gefE3 and PC‐9/gefE7 cells.

PPAR-γ; 

PubMed: 23409107     


Fold increase relative to control was determined after normalization with β-actin as external loading control. 

22586683 18559346 23102728 23409107
Immunofluorescence
EGFR / LC3; 

PubMed: 31196210     


H157 and H1299 cells were treated with gefitinib, or curcumin alone, or gefitinib plus curcumin at indicated concentration for 48 h and then were fixed with methanol, immunostained with anti-EGFR (green), anti-LC3 (red), and DAPI (blue), and analyzed by confocal microscopy to determine the intracellular locations of EGFR and LC3.

PPAR-γ; 

PubMed: 23409107     


Upregulation and nuclear accumulation of PPARγ following treatment with gefitinib (24 hs).

p-EGFR / β-catenin; 

PubMed: 23461856     


In untreated CNE2 cells, β-catenin was located in cytoplasmic membranes and cytoplasm. Treatment with EGF (50 ng/mL) resulted in increased β-catenin nuclear staining, which was reversed by either gefitinib (1 μM) or LY294002 (15 μM). 

31196210 23409107 23461856
Growth inhibition assay
GI50; 

PubMed: 23409107     


Dose-response of bladder cancer cell lines to EGFR inhibitor (gefitinib). The GI50 value was defined as the mean concentration of drug that generates 50% of growth inhibition as compared to controls.

23409107
In vivo

Gefitinib (100 mg/kg) improves the anti-tumor effect of radiotherapy in LoVo tumor xenografts. [3] Gefitinib treatment of nude mice bearing established human GEO colon cancer xenografts reveals a reversible dose-dependent inhibition of tumor growth because GEO tumors resumes the growth rate of controls at the end of the treatment. [4]

Protocol

Cell Research:

[1]

- Collapse
  • Cell lines: NR6, NR6M and NR6W cells
  • Concentrations: 0-2 μM
  • Incubation Time: 72 hours
  • Method:

    Exponentially growing cells including NR6, NR6M, NR6M and NR6W cells are seeded in sextuple in 96-well plates at a concentration of 2000 cells/well, allowed to adhere and subsequently washed in PBS and incubated overnight in medium containing 0.5% FCS. Cells are then treated with varying concentrations (0-2 μM) of Gefitinib or the solute control DMSO and EGF. The optimal EGF concentration for inducing proliferation of NR6wtEGFR and NR6W cells has previously been determined and hence NR6wtEGFR and NR6W cells are supplemented with 10 nM and 0.1 nM EGF, respectively. EGF is not added to NR6 and NR6M cells. After 72 hours the amount of cells are measured by performing a MTT proliferation assay.


    (Only for Reference)
Animal Research:

[3]

- Collapse
  • Animal Models: Female nude mice (cba nu/nu) aged 8–10 weeks are intra-dermal injected with LoVo cells.
  • Dosages: 100 mg/kg
  • Administration: Once daily by oral administration (0.1 mL/10 g body weight) for 14 days
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 89 mg/mL (199.14 mM)
Ethanol 4 mg/mL (8.95 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
1% CMC Na
For best results, use promptly after mixing.
30mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 446.90
Formula

C22H24ClFN4O3

CAS No. 184475-35-2
Storage powder
in solvent
Synonyms Iressa
Smiles COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03292133 Recruiting Drug: EGF816|Drug: Gefitinib Lung Cancer Massachusetts General Hospital|Novartis October 31 2017 Phase 2
NCT03122717 Active not recruiting Drug: Gefitinib|Drug: Osimertinib Non-Small Cell Lung Cancer Dana-Farber Cancer Institute|AstraZeneca May 9 2017 Phase 1|Phase 2
NCT02932345 Completed -- EGFR Mutation Positive Advanced Non-small-cell Lung Cancer AstraZeneca October 31 2016 --
NCT02824458 Recruiting Drug: Apatinib|Drug: Gefitinib|Drug: Placebo EGFR Tyrosine Kinase Inhibitors Plus VEGFR Inhibitors Sun Yat-sen University June 2016 Phase 3
NCT02804100 Unknown status -- Carcinoma Non-Small-Cell Lung|Bronchial Neoplasms|Carcinoma Bronchogenic|Lung Diseases|Lung Neoplasms Wenzhou Medical University May 2016 --

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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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Frequently Asked Questions

  • Question 1:

    I try to dissolve Gefitinib (ZD1839) in 0.5% methylcellulose+0.2% Tween 80 for in vivo experiments. However, when I prepare the mixture, it forms precipitates. Exists another way to dissolve completely the compound?

  • Answer:

    S1025 can be dissovled in both 5% DMSO+corn oil and 5% DMSO+30% PEG 300+5% Tween 80+ddH2O at 2.5 mg/ml clearly. It dissolves in DMSO not readily, please sonicate and warm it in water bath at about 45 degree, and dissolve it clearly first. Then add other solvent.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID