| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
TAK-285 (TAK285), currently being investigated by Takeda company, is a dual HER2/EGFR(HER1) inhibitor with potential antitumor activity. Its IC50 values for HER2/1 inhibition are 17 nM and 23 nM. More than ten times more selective for HER1/2 than HER4, it is less effective against MEK1/5, Aurora B, Lck, c-Met, CSK, and other substances.
| Targets |
HER2 (IC50 = 17 nM); EGFR/HER1 (IC50 = 23 nM); HER4 (IC50 = 260 nM); MEK1 (IC50 = 1.1 μM); Aurora B (IC50 = 1.7 μM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
The cytoplasmic domains of human HER2 (amino acids 676–1255) and human EGFR (amino acids 669–1210) are expressed via a baculovirus expression system as N-terminal peptide (DYKDDDD)-tagged protein. Anti-FLAG M2 affinity gel is used to separate the expressed EGFR and HER2 kinases. Radiolabeled [γ-32P]ATP is used in 96-well plates for the EGFR and HER2 kinase assays. Each purified cytoplasmic domain (0.25 μg/mL EGFR or HER2) in a total volume of 50 μL, 50 μM ATP, 5 ug/mL poly(Glu)-Tyr (4:1), and 0.9 uCi of [γ-32P]ATP per reaction are added to the 50 μL of Tris-HCl (pH 7.5), 0.01% Tween 20, and 2 mM DTT. The enzyme is incubated with increasing concentrations of TAK-285 for five minutes at room temperature before the reaction is measured to determine the IC50 value for enzyme inhibition. ATP is added to start the kinase reactions. The reactions are halted by adding 10% (final concentration) trichloroacetic acid after 10 minutes at room temperature. After using a cell harvester to filter the γ-32P phosphorylated proteins in a harvest plate, 3% phosphoric acid is used to remove any remaining [γ-32P]ATP. MicroScint0 (25 μL) is added to the plates after they have dried. A TopCount scintillation counter measures radioactivity. The nonlinear regression analysis of the percent inhibitions is used to compute the IC50 values.
|
|
| Cell Assay |
For five days, the cells are continuously treated with TAK-285 at different concentrations. A particle analyzer is used to count the number of live cells.
|
|
| Animal Protocol |
Female BALB/c nu/nu mice bearing BT-474 or 4-1ST xenografts, and female nude rats (F344/N Jcl-rnu) bearing 4-1ST xenografts
~100 mg/kg/day Orally twice daily |
|
| References | ||
| Additional Infomation |
EGFR/HER2 Kinase Inhibitor TAK-285 is an orally bioavailable, small molecule and dual kinase inhibitor of human epidermal growth factor receptors 1 (EGFR/ErbB1) and 2 (HER2/ErbB2), with potential antineoplastic activity. EGFR/HER2 kinase inhibitor TAK-285 binds to and inhibits EGFR and HER2, which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. This agent may be active against EGFR/HER2-expressing tumor cells that are resistant to trastuzumab. EGFR and HER2, receptor tyrosine kinases overexpressed in a variety of tumor cell types, play major roles in tumor cell proliferation and tumor vascularization. In addition, TAK-285 appears to pass the blood brain barrier (BBB) and does not appear to be a substrate for efflux pumps.
|
| Molecular Formula |
C26H25CLF3N5O3
|
|
|---|---|---|
| Molecular Weight |
547.96
|
|
| Exact Mass |
547.159
|
|
| Elemental Analysis |
C, 56.99; H, 4.60; Cl, 6.47; F, 10.40; N, 12.78; O, 8.76
|
|
| CAS # |
871026-44-7
|
|
| Related CAS # |
|
|
| PubChem CID |
11620908
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Boiling Point |
705.5±60.0 °C at 760 mmHg
|
|
| Melting Point |
167-169℃
|
|
| Flash Point |
380.4±32.9 °C
|
|
| Vapour Pressure |
0.0±2.4 mmHg at 25°C
|
|
| Index of Refraction |
1.608
|
|
| LogP |
3.56
|
|
| Hydrogen Bond Donor Count |
3
|
|
| Hydrogen Bond Acceptor Count |
9
|
|
| Rotatable Bond Count |
9
|
|
| Heavy Atom Count |
38
|
|
| Complexity |
792
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
O=C(CC(C)(C)O)NCCN1C2C(=NC=NC=2NC2C=C(Cl)C(OC3C=C(C(F)(F)F)C=CC=3)=CC=2)C=C1
|
|
| InChi Key |
ZYQXEVJIFYIBHZ-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C26H25ClF3N5O3/c1-25(2,37)14-22(36)31-9-11-35-10-8-20-23(35)24(33-15-32-20)34-17-6-7-21(19(27)13-17)38-18-5-3-4-16(12-18)26(28,29)30/h3-8,10,12-13,15,37H,9,11,14H2,1-2H3,(H,31,36)(H,32,33,34)
|
|
| Chemical Name |
N-[2-[4-[3-chloro-4-[3-(trifluoromethyl)phenoxy]anilino]pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-3-hydroxy-3-methylbutanamide
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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 (4.56 mM) (saturation unknown) 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. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8250 mL | 9.1248 mL | 18.2495 mL | |
| 5 mM | 0.3650 mL | 1.8250 mL | 3.6499 mL | |
| 10 mM | 0.1825 mL | 0.9125 mL | 1.8250 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00535522 | Completed | Drug: TAK-285 Dose Escalation Cohorts Drug: TAK-285 Recommended Phase 2 Dosing Cohort |
Cancer | Millennium Pharmaceuticals, Inc. | August 2007 | Phase 1 |
Overall structure of HER2·SYR127063 and EGFR·TAK-285.J Biol Chem.2011 May 27;286(21):18756-65. |
Origins of α-helix C conformational flexibility in HER2.J Biol Chem.2011 May 27;286(21):18756-65. |
HER2 and EGFR mechanism of inhibition.J Biol Chem.2011 May 27;286(21):18756-65. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
