| Identification | Back Directory | [Name]
AMG319 | [CAS]
1608125-21-8 | [Synonyms]
AMG319
ACP319
ACP-319
CS-1593
ACP 319
AMG-319;AMG 319;AMG319
AMG319; AMG-319; AMG 319; ACP319; ACP-319; ACP 319;
(S)-N-(1-(7-Fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine
(αS)--Fluoro-α-methyl-N-9H-purin-6-yl-2-(2-pyridinyl)-3-quinolinemethanamine
3-Quinolinemethanamine, 7-fluoro-α-methyl-N-9H-purin-6-yl-2-(2-pyridinyl)-, (αS)-
(alphaS)-7-Fluoro-alpha-methyl-N-9H-purin-6-yl-2-(2-pyridinyl)-3-quinolinemethanamine | [Molecular Formula]
C21H16FN7 | [MDL Number]
MFCD28902228 | [MOL File]
1608125-21-8.mol | [Molecular Weight]
385.4 |
| Chemical Properties | Back Directory | [Boiling point ]
708.3±60.0 °C(Predicted) | [density ]
1.432±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
crystalline solid | [pka]
9.99±0.10(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
AMG319 is a potent and selective PI3Kδ kinase inhibitor with IC50 of 18 nM. | [Biological Activity]
amg 319, a highly selective inhibitor of phosphoinositide 3-kinase p110δ isoform (pi3kδ) [1], with an ic50 value less than 10 nm [2].pi3kδ plays an essential role in b-cell receptor (bcr) signaling. pi3kδ is expressed in lymphoid malignancies, including chronic lymphocytic leukemia (cll) and non-hodgkin lymphoma (nhl) [1].c-akt, a serine-threonine kinase is one target of pi39k. c-akt is the prototypical member of a mammalian akt isoform family. the regulation to akt may be phosphorylation or direct binding the akt pleckstrin homology domain with pi39k lipid products. pi39k-independent akt stimuli had been identified [3]. amg 319 inhibited basal akt phosphorylation and proliferation in lymphoid tumor cells [1].28 patients received amg 319. in a cll patient after 1 dose of amg 319, grade 3 hemolytic anemia at 25 mg was produced. all cll samples with an inducible signal (60%) showed coverage of bcr-induced pakt (ex-vivo igd stimulated) dose-dependently; at 400 mg, near complete inhibition was seen for 24 hours. baseline % of t-regulatory cells was elevated in cll patients (14.4% ± 7.6%). but during treatment (14/19 patients), the elevated t regulatory cells tended to normalize. this suggested that the drug might produce immune restoration. by physical exam, all 20 evaluable patients showed greater than 50% lymph node (ln) reduction, 15 (75%) patients showed greater than 90% ln reduction. this response was present in all cytogenetic subtypes [1]. | [in vivo]
The study is performed to determine the correlation between biochemical coverage (i.e., pAKT) with functional activity in vivo. AMG319 achieves this coverage at the 3 mg/kg level, which also coveres the human whole blood assay (HWB) (CD-69) IC90 at trough for a full 24 h period. The lower doses 0.1, 0.3, and 1 mg/kg cover trough concentrations between the HWB IC50 and IC90 and evince partial efficacy. Similarly, the plasma concentration of AMG319 covers the IC90 at the 1 mg/kg dose of the mouse anti-IgM pAKT in vitro assay[1]. | [IC 50]
PI3Kδ: 18 nM (IC50); PI3Kγ: 850 nM (IC50); PI3Kβ: 2.7 μM (IC50); PI3Kα: 33 μM (IC50) | [storage]
Store at -20°C | [References]
[1]. glenn m, mato ar, allgood sd, et al. first-in-human study of amg 319, a highly selective, small molecule inhibitor of pi3kδ, in adult patients with relapsed or refractory lymphoid malignancies. blood, 2013, 122(21): 678-678.
[2]. brana i, siu ll. clinical development of phosphatidylinositol 3-kinase inhibitors for cancer treatment. bmc medicine, 2012, 10(1): 1.
[3]. datta sr, dudek h, tao x, et al. akt phosphorylation of bad couples survival signals to the cell-intrinsic death machinery. cell, 1997, 91(2): 231-241. |
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| Company Name: |
Twochem Co.Ltd.
|
| Telephone: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
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