| Identification |
| Chemical Name |
AG-490 |
| Accession Number |
HAMDB188 |
| Alternative Names |
AG 490;Tyrphostin AG 490;AG490 |
| IUPAC Name |
(E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enamide |
| Formula |
C17H14N2O3 |
| Canonical SMILES |
C1=CC=C(C=C1)CNC(=O)C(=CC2=CC(=C(C=C2)O)O)C#N |
| Structure |
CNC(=O)C(=CC2=CC(=C(C=C2)O)O)C#N/PNG)
|
| Physicochemical Properties |
| Molecular Weight |
294.305Molecular weight |
| Hbond Donor |
3Number of hydrogen bond acceptor atoms
(not counting acidic atoms but counting atoms that are both hydrogen bond donors and acceptors such as -OH).
|
| Hbond Acceptor |
4
Number of hydrogen bond donor atoms (not counting basic atoms but counting atoms that are both hydrogen bond donors and acceptors such as -OH).
|
| logP (o/w) |
2.462
Log of the octanol/water partition coefficient (including implicit hydrogens). [LOGP 1998]
|
| logS |
-3.468
Log of the aqueous solubility (mol/L).
|
| MR |
8.381
Molecular refractivity (including implicit hydrogens).
|
| SlogP |
2.588
Log of the octanol/water partition coefficient. [Crippen 1999]
|
| TPSA |
93.350
Polar surface area (Å2) calculated using group contributions to approximate the polar surface area from connection table information only. The parameterization is that of Ertl et al. [Ertl 2000].
|
| logD (PH=7) |
3.142
The octanol/water distribution coefficient at pH 7.
|
| pKa (PH=7) |
7.238
The pKa of the reaction that removes a proton from the ensemble of states with a hydrogen count equal to the input structure.
|
| pKb (PH=7) |
14.000
The pKb of the reaction that adds a proton from the ensemble of states with a hydrogen count equal to the input structure.
|
| Lipinski druglike |
1
One if and only if lip_violation < 2 otherwise zero.
|
| Solubility |
10 mM in DMSO |
| Role in Autophagy |
| Not Available |
| Biological Behaviors |
| Gene Name |
STAT1; EGFR |
| Target |
Autophagy; STAT; STAT; EGFR; EGFR; |
| Pathway |
- Autophagy
- Stem Cells/Wnt
- JAK/STAT Signaling
- Protein Tyrosine Kinase/RTK
- JAK/STAT Signaling
|
| Biological Description |
AG-490 (Tyrphostin AG 490) is an inhibitor of EGFR with IC50 of 0.1 μM, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.
IC50 value: 0.1 uM (EGFR)[1]; 10 uM (JAK2) [2]
Target: EGFR
in vit |
| Research Area |
Cancer |
| Category |
Activator |
| In Vitro |
AG490 inhibits the activation of Stat-3 by selectively blocking JAK2. AG490 is used to selectively inhibit JAK/Stat-3 activation. At a dose of 10 μM, Stat-3 phosphorylation is decreased by >95% and cell viability is maintained. AG490 at a dose of 10 μM results in >95% decrease in pStat-3 in EGF-stimulated A431 cells with no effect on Stat-3 mass. AG-490 is a potent inhibitor of the JAK3/STAT, JAK3/AP-1, and JAK3/MAPK pathways and their cellular consequences. AG-490 abolishes IL-2-inducible [3H]thymidine incorporation in a dose-dependent manner, displaying an IC50 of 25 μM. AG-490 potently inhibits IL-2-mediated proliferation in T cells, results distinct from previous studies that showed this agent induced apoptosis in ALL cells while exerting apparently no effects on the growth of mitogen-stimulated normal T cells. |
| In Vivo |
AG490 significantly inhibits the development of type 1 diabetes (T1D) (p = 0.02, p = 0.005; at two different time points). Monotherapy of newly diagnosed diabetic NOD mice with AG490 (1 mg/mouse) markedly results in disease remission in treated animals (n=23) in comparision to the absolute inability (0%; 0/10, p=0.003, Log-rank test) of DMSO and sustained eugluycemia is maintained for several months following drug withdrawal. AG490 (1-10 µg) significantly attenuates ʎ-carrageenan-induced thermal hyperalgesia in a dose-dependent manner. AG490 also reduces mechanical hyperalgesia. |
| Clinical Trial |
Not Available |
| External Links |
| CAS Numbers |
133550-30-8 |
| Pubchem |
5328779 |
| HMDB |
Not Available |
| DrugBank |
Not Available |
| References |
- Dowlati A, Nethery D, Kern Ja, Combined Inhibition Of Epidermal Growth Factor Receptor And Jak/stat Pathways Results In Greater Growth Inhibition In Vitro Than Single Agent Therapy., Mol Cancer Ther.2004 Apr;3(4):459-63. [PMID:15078989 ]
- Wang Lh, Kirken Ra, Erwin Ra, Yu Cr, Farrar Wl, Jak3, Stat, And Mapk Signaling Pathways As Novel Molecular Targets For The Tyrphostin Ag-490 Regulation Of Il-2-mediated T Cell Response., J Immunol.1999 Apr 1;162(7):3897-904. [PMID:10201908 ]
- Davoodi-semiromi A, Wasserfall Ch, Xia Cq, Cooper-dehoff Rm, Wabitsch M, Clare-salzler M, Atkinson M, The Tyrphostin Agent Ag490 Prevents And Reverses Type 1 Diabetes In Nod Mice., Plos One.2012;7(5):e36079. Doi: 10.1371/journal.pone.0036079. [PMID:22615750 ]
- Cheppudira Bp, Garza Th, Petz Ln, Clifford Jl, Fowler M, Anti-hyperalgesic Effects Of Ag490, A Janus Kinase Inhibitor, In A Rat Model Of Inflammatory Pain., Biomed Rep.2015 Sep;3(5):703-706. [PMID:26405549 ]
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