6-氯-5-[[(2R,5S)-4-[(4-氟苯基)甲基]-2,5-二甲基-1-哌嗪基]甲酰基]-N,N,1-三甲基-A

中文名称:

6-氯-5-[[(2R,5S)-4-[(4-氟苯基)甲基]-2,5-二甲基-1-哌嗪基]甲酰基]-N,N,1-三甲基-ALPHA-氧代-1H-吲哚-3-乙酰胺

中文同义词:

6-氯-5-[[(2R,5S)-4-[(4-氟苯基)甲基]-2,5-二甲基-1-哌嗪基]甲酰基]-N,N,1-三甲基-ALPHA-氧代-1H-吲哚-3-乙酰胺;他匹莫德;P38抑制剂(SCIO-469)

英文名称:

talmapimod

英文同义词:

TALMAPIMOD;SCIO469;SCIO 469;SCIO 469 - Talmapimod;talmapimod;6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-alpha-oxo-1H-indole-3-acetamide;Unii-B1E00kq6nt;6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-Indole-3-acetamidehydrochloride;SCIO 469 hydrochloride;6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)Methyl]-2,5-diMethyl-1-piperazinyl]carbonyl]-N,N,1-triMethyl-α-oxo-1H-indole-3-acetaMide

CAS号:

309913-83-5

分子式:

C27H30ClFN4O3

分子量:

513

EINECS号:

相关类别:

细胞生物学试剂

Mol文件:

309913-83-5.mol

沸点 

658.0±65.0 °C(Predicted)

密度 

1.29

储存条件 

Desiccate at +4°C

酸度系数(pKa)

6.52±0.70(Predicted)

生物活性

Talmapimod (SCIO-469) 是 p38α 选择性的，具有口服活性的，ATP 竞争性的抑制剂，IC50 值是 9 nM，约为 p38β 的10倍，在 20 个其他激酶 (包括其他 MAPKs) 上显示出至少 2000 倍的选择性。

靶点

p38α 9 nM (IC 50 ) p38β 90 nM (IC 50 )

p38α 9 nM (IC 50 )

p38β 90 nM (IC 50 )

体外研究

Talmapimod (SCIO-469) (100-200 nM; 1 hour) inhibits phosphorylation of p38 MAPK in MM cells. Talmapimod inhibits LPS-induced TNF-a production in human whole blood. Talmapimod decreases constitutive p38alpha MAPK phosphorylation of both 5T2MM and 5T33MM cells. Western Blot Analysis Cell Line: MM.1S, U266, RPMI8226, MM.1R, and RPMI-Dox40 cell lines Concentration: 100, 200 nM Incubation Time: 1 hour Result: Strongly inhibits phosphorylation of p38 MAPK.

Cell Line:

MM.1S, U266, RPMI8226, MM.1R, and RPMI-Dox40 cell lines

Concentration:

100, 200 nM

Incubation Time:

1 hour

Result:

Strongly inhibits phosphorylation of p38 MAPK.

体内研究

Targeting p38α MAPK with Talmapimod (SCIO-469) decreases myeloma burden in addition to preventing the development of myeloma bone disease. Talmapimod inhibits multiple myeloma growth and prevents bone disease in the 5T2MM and 5T33MM models. Talmapimod (10-90 mg/kg; p.o.; twice daily orally for 14 days) dose-dependently reduced tumor growth and also dose-dependently reduced weight of the palpable tumors at termination. Animal Model: Six-week-old male triple immune-deficient BNX mice (RPMI-8226 MM palpable tumors) Dosage: P.o.; twice daily orally for 14 days Administration: 10, 30, 90 mg/kg Result: Dose-dependently reduced tumor growth.

Animal Model:

Six-week-old male triple immune-deficient BNX mice (RPMI-8226 MM palpable tumors)

Dosage:

P.o.; twice daily orally for 14 days

Administration:

10, 30, 90 mg/kg

Result:

Dose-dependently reduced tumor growth.