BenzaMide, N-[[(3S)-3-aMino-1-(5-ethyl-7H-pyrrolo[2,3-d]pyriMidin-4-yl)-3-pyrrolidinyl]Methyl]-2,4-difluoro-
(S)-N-[[3-Amino-1-(5-ethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]methyl]-2,4-difluorobenza
CAS: 1004990-28-6
Molecular Formula: C20H22F2N6O
BenzaMide, N-[[(3S)-3-aMino-1-(5-ethyl-7H-pyrrolo[2,3-d]pyriMidin-4-yl)-3-pyrrolidinyl]Methyl]-2,4-difluoro- - Names and Identifiers
BenzaMide, N-[[(3S)-3-aMino-1-(5-ethyl-7H-pyrrolo[2,3-d]pyriMidin-4-yl)-3-pyrrolidinyl]Methyl]-2,4-difluoro- - Physico-chemical Properties
| Molecular Formula | C20H22F2N6O |
| Molar Mass | 400.43 |
| Density | 1.353 |
| Storage Condition | 2-8℃ |
| In vitro study | PF-AKT400 (Compound 42) provides significantly enhanced selectivity for Akt relative to earlier leads such as spiroindoline 2. Free IC 50 and EC 50 values are estimated for phospho-S6 reduction (110 nM) and Akt hyperphosphorylation (216 nM), respectively. These values corresponded well to the cellular IC 50 for PF-AKT400 in U87 cells measuring p-GSK-3α (310 nM). |
| In vivo study | PF-AKT400 is subsequently evaluated for modulation of Akt in tumors and in multiple in vivo mouse models of antitumor efficacy. It is active in a PC3 prostate carcinoma xenograft experiment, with 75% TGI observed at 100 mg/kg b.i.d. dosing for 10 days. In a colorectal carcinoma (Colo205) xenograft study, PF-AKT400 produces 60% TGI at 150 mg/kg b.i.d. after 10 days. Most intriguingly, in combination with Rapamycin (10 mg/kg, ip), 75 mg/kg b.i.d. (10 days) of PF-AKT400 results in 98% TGI in an additional PC3 prostate carcinoma xenograft study compared to 56% TGI and 66% TGI with PF-AKT400 and Rapamycin as single agents. To define the in vivo potency of PF-AKT400 (Compound 42) in the PC3 xenograft model, oral administration of 25, 75, and 100 mg/kg PF-AKT400 is performed with blood and tumor sampling over time. Immunoblot analysis of detergent-soluble extracts derived from PC3 tumors shows a significant reduction of S6 phosphorylation, and hyperphosphorylation of Akt upon treatment at doses that produced significant tumor growth inhibition. Plasma drug concentrations peak rapidly after oral administration of doses between 25-100 mg/kg (T max =0.5 h). Peak PD responses of phospho-S6 and phospho-Akt are observed at approximately 2-4h and 1h post-administration of PF-AKT400, respectively. The time-course of PD marker response is well described by a PK/PD model at doses that ranged from no efficacy (25 mg/kg) to maximal efficacy (100 mg/kg). |
BenzaMide, N-[[(3S)-3-aMino-1-(5-ethyl-7H-pyrrolo[2,3-d]pyriMidin-4-yl)-3-pyrrolidinyl]Methyl]-2,4-difluoro- - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.497 ml | 12.487 ml | 24.973 ml |
| 5 mM | 0.499 ml | 2.497 ml | 4.995 ml |
| 10 mM | 0.25 ml | 1.249 ml | 2.497 ml |
| 5 mM | 0.05 ml | 0.25 ml | 0.499 ml |
Last Update：2024-01-02 23:10:35
BenzaMide, N-[[(3S)-3-aMino-1-(5-ethyl-7H-pyrrolo[2,3-d]pyriMidin-4-yl)-3-pyrrolidinyl]Methyl]-2,4-difluoro- - Reference Information
| biological activity | PF-AKT400 is an effective, ATP-competitive selective Akt inhibitor, and its selectivity for PKB α (IC50=0.5 nM) is 900 times higher than PKA (IC50=450 nM). |
| target | PKB α 0.5 nM (IC 50 ) PKA 450 nM (IC 50 ) |
| in vitro study | PF-AKT400 (Compound 42) provides significantly enhanced selectivity for Akt relative to earlier lead such as spiroindoline 2. Free IC 50 and EC 50 values are estimated for phospho-S6 reduction (110 nM) and Akt hyperphosphorylation (216 nM), respectively. These values corresponded well to the cellular IC 50 for PF-AKT400 in U87 cells measuring p-GSK-3 α (310 nM). |
| in vivo research | PF-AKT400 is subsequently evaluated for modulation of Akt in tumors and in multiple in vivo mouse models of antitumor efficacy. It is active in a PC3 prostate carcinoma xenograft experiment, with 75% TGI observed at 100 mg/kg B. I. d. dosing for 10 days. In a colorectal carcinoma (Colo205) xenograft study, PF-AKT400 produces 60% TGI at 150 mg/kg B. I. d. after 10 days. Most intriguingly, in combination with Rapamycin (10 mg/kg, ip), 75 mg/kg B. I. d. (10 days) of PF-AKT400 results in 98% TGI in an additional PC3 prostate carcinoma xenograft study compared to 56% TGI and 66% TGI with PF-AKT400 and Rapamycin as single agents. To define the in vivo potency of PF-AKT400 (Compound 42) in the PC3 xenograft model, ooral administration of 25, 75, and 100 mg/kg PF-AKT400 is performed with blood and tumor sampling over time. Immunoblot analysis of detergent-soluble extracts derived from PC3 tumors shows a significant reduction of S6 phosphorylation, and hyperphosphorylation of Akt upon treatment at dos that produced significant tumor growth inhibition. Plasma drug concentrations peak rapidly after oral administration of dos between 25-100 mg/kg (T max = 0.5 h). Peak PD responses of phospho-S6 and phospho-Akt are observed at approximately 2-4h and 1h post-administration of PF-AKT400, respectively. The time-course of PD marker response is well described by a PK/PD model at dos that efficacy (25 mg/kg) to maximal efficacy (100 mg/kg). |
Last Update：2024-04-09 20:52:54
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Product Name: (S)-N-[[3-Amino-1-(5-ethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]methyl]-2,4-difluorobenza Visit Supplier Webpage Request for quotation
CAS: 1004990-28-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 1004990-28-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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