TAK-733
Description In vitro In vivo- Product Name
- TAK-733
- CAS No.
- 1035555-63-5
- Chemical Name
- TAK-733
- Synonyms
- CS-547;TAK-733;TAK-733 ，S2617;TAK-733/TAK733;TAK-733 USP/EP/BP;TAK-733, 10 mM in DMSO;(R)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrim;3-[(2r)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione;(R)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione;Pyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione, 3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-8-methyl-
- CBNumber
- CB42561497
- Molecular Formula
- C17H15F2IN4O4
- Formula Weight
- 504.23
- MOL File
- 1035555-63-5.mol
TAK-733 Property
- Boiling point:
- 530.5±60.0 °C(Predicted)
- Density
- 1.91±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- ≥25.2 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
- form
- solid
- pka
- 13.72±0.20(Predicted)
- color
- White to light yellow
Safety
- HS Code
- 2933399990
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P280Wear protective gloves/protective clothing/eye protection/face protection.
P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P302+P352IF ON SKIN: wash with plenty of soap and water.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- 16998
- Product name
- TAK-733
- Purity
- ≥98%
- Packaging
- 500μg
- Price
- $33
- Updated
- 2024/03/01
- Product number
- 16998
- Product name
- TAK-733
- Purity
- ≥98%
- Packaging
- 1mg
- Price
- $60
- Updated
- 2024/03/01
- Product number
- 16998
- Product name
- TAK-733
- Purity
- ≥98%
- Packaging
- 5mg
- Price
- $208
- Updated
- 2024/03/01
- Product number
- 16998
- Product name
- TAK-733
- Purity
- ≥98%
- Packaging
- 10mg
- Price
- $380
- Updated
- 2024/03/01
- Product number
- BISN0162
- Product name
- TAK-733
- Packaging
- 2mg
- Price
- $102
- Updated
- 2021/12/16
TAK-733 Chemical Properties,Usage,Production
Description
TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc. Phase 1.
In vitro
TAK-733 is highly potent and selective MEK allosteric site inhibitor with IC50 of 3.2 nM. TAK-733 shows potent enzymatic and cell activity with an EC50 of 1.9 nM against ERK phosphorylation in cells.
In vivo
TAK-733 demonstrates broad antitumor activity in mouse xenograft models of human cancer including models of melanoma, colorectal, NSCLC, pancreatic and breast cancer. TAK-733 is well tolerated with pharmacokinetics and pharmacodynamics that support once-daily oral dosing in humans. TAK-733 shows maximally efficacious doses at once daily orally doses of 10 mg/kg.
Uses
TAK-733 is a potent and selective MEK allosteric site inhibitor with an IC50 of 3.2 nM.
Biological Activity
tak-733 is a potent, atp-noncompetitive and selective inhibitor of mek allosteric site with the ic50 value of 3.2nm [1].tak-733 has been shown potent enzymatic and cell activity with an ic50 value of 3.2nm against constitutively active mek enzyme and an ec50 of 1.9nm against erk phosphorylation in cells. in addition, tak-733 has also shown the low clearance and high oral bioavailability based on the pharmacokinetics of tak-733 in all species (mouse, rat, dog and monkey). furthermore, tak-733 has been reported to broad inhibit tumor activity in mouse xenograft models of human cancer (melanoma, colorectal, nsclc, pancreatic and breast cancer) [1].
Synthesis
1035555-51-1
1035555-63-5
Example 18: (i) To a solution of 3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidin-4,7(3H,8H)-dione (Example 6) (1 g, 2.06 mmol, 1 eq.) in DMF (19 mL) was added dropwise under nitrogen protection at ambient temperature a solution of Selectfluor (801 mg, 2.26 mmol, 1.1 eq.) in a mixture of acetonitrile (9 mL) and DMF (5 mL). The reaction mixture was stirred at ambient temperature for 10 minutes and then filtered. The filtrate was purified by preparative LC/MS (30-55% CH3CN/H2O) to afford (R)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (Example 18) as an off-white solid. The recovered feedstock was reacted under the same reaction conditions to give a second batch of product. The total yield was 347 mg (33%).1H NMR (400 MHz, DMSO-J6) δ ppm 3.36-3.40 (m, 1H), 3.43-3.50 (m, 1H), 3.58 (s, 3H), 3.61-3.72 (m, 1H), 3.72-3.82 (m, 1H), 4.27-4.37 (m, 1H) , 4.78-4.87 (m, 1H), 5.14 (d, J = 5.81 Hz, 1H), 6.93-7.03 (m, 1H), 7.53 (d, J = 8.84 Hz, 1H), 7.65-7.74 (m, 1H), 8.52 (s, 1H), 10.25 (d, J = 10.1 Hz, 1H). The calculated value for [M + H] C17H15F2IN4O4 is 505; the measured value is 505.
in vivo
The pharmacokinetics of TAK-733 is evaluated in nude mouse, rat, dog and monkey. Low clearance and high oral bioavailability are observed in all species. TAK-733 demonstrates broad antitumor activity in mouse xenograft models of human cancer including models of melanoma, colorectal, NSCLC, pancreatic and breast cancer[1]. Daily oral administration of 1, 3, 10, and 30 mg/kg of TAK-733 for 14 days (Days 10 to 23) results in tumor growth delay in the A375 cell-implanted mice (5/group). TAK-733 (35, 70, 100, and 160 mg/kg) also significantly inhibits tumor growth on an intermittent dosing schedule of 3 days per week for 2 weeks (Days 10, 13, 15, 17, 20, and 22). Three partial regressions (PR), a 60% response rate, are observed in mice administered with 30 mg/kg of TAK-733 daily and in mice administered with 160 mg/kg of TAK-733 intermittently. Responses, CR (complete regression) and partial regressions (PR) are also observed in mice administered with 70, 100, and 160 mg/kg of TAK-733 intermittently. The tumor regression rate is more pronounced with the intermittent administration regimen; the greatest reduction in tumor volume is observed at 160 mg/kg (57.29%), versus a maximum reduction of 46.97% at 30 mg/kg once daily. By the last day of administration, tumor growth is significantly (p<0.05 for %T/C, Student's t-test) inhibited in mice administered 3, 10, and 30 mg/kg once daily or 35, 70, 100, and 160 mg/kg intermittently[2].
target
MEK1
IC 50
MEK: 3.2 nM (IC50)
References
[1] dong q1, dougan dr, gong x, halkowycz p, jin b, kanouni t, o'connell sm, scorah n, shi l, wallace mb, zhou f. discovery of tak-733, a potent and selective mek allosteric site inhibitor for the treatment of cancer. bioorg med chem lett. 2011 mar 1;21(5):1315-9. doi: 10.1016/j.bmcl.2011.01.071. epub 2011 jan 22.
TAK-733 Preparation Products And Raw materials
Raw materials
Preparation Products
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View Lastest Price from TAK-733 manufacturers
- Product
- TAK-733 1035555-63-5
- Price
- US $3.00/KG
- Min. Order
- 1KG
- Purity
- 99%
- Supply Ability
- 100kg
- Release date
- 2019-08-06