WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200121
CAS#: 133550-30-8
Description: Tyrphostin AG490 is a JAK-2 specific inhibitor, which inhibits phosphorylation of EGFR and signal transducer and activator of transcription 3 [STAT-3], and subsequently reduce invasion and adhesion potential of malignant cells. The hematopoietic cancer c-Kit+, Jak-2+ and non hematopoietic tumors c-Kit+, HER-2+, JAK-2+ can be inhibited by the chemosensitizing agent AG490 causing programmed cell death.
MedKoo Cat#: 200121
Name: AG-490
CAS#: 133550-30-8
Chemical Formula: C17H14N2O3
Exact Mass: 294.10044
Molecular Weight: 294.3
Elemental Analysis: C, 69.38; H, 4.79; N, 9.52; O, 16.31
Synonym: AG 490; AG490; AG-490; Tyrphostin AG 490
IUPAC/Chemical Name: (E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide
InChi Key: TUCIOBMMDDOEMM-RIYZIHGNSA-N
InChi Code: InChI=1S/C17H14N2O3/c18-10-14(8-13-6-7-15(20)16(21)9-13)17(22)19-11-12-4-2-1-3-5-12/h1-9,20-21H,11H2,(H,19,22)/b14-8+
SMILES Code: O=C(NCC1=CC=CC=C1)/C(C#N)=C/C2=CC=C(O)C(O)=C2
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | AG490 (Tyrphostin AG490) is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3. |
| In vitro activity: | To explore the effect of blocking p-JAK2 on TNF-α-induced apoptosis in MC3T3-E1 cells, cells were pretreated with AG490 (0, 10, 20, and 40 μM), a specific JAK2 inhibitor, for 30 min before incubation with TNF-α (20 ng/ml, 48 h). Then, flow cytometry was performed after Annexin V and PI labeling. The results showed that AG490 significantly increased the percentage of apoptotic cells (Figs. 3A and B). Western blot analysis was used to detect p-JAK2, JAK2, and Cl-PARP expression. JAK2 phosphorylation decreased and reached the lowest point at 40 μM concentration. Meanwhile, the level of Cl-PARP increased (Figs. 3C–E). These results indicate that JAK2-blockage increases TNF-α-induced apoptosis in MC3T3-E1 cell. Reference: Pharmazie. 2020 Jun 1;75(6):255-260. https://pubmed.ncbi.nlm.nih.gov/32539921/ |
| In vivo activity: | Besides the effect of AG490 on neuroprotection against apoptosis, this study also observed the alternations of neurotrophins mediated by the inhibitor for neural repairment. The results from ELISA tests revealed that the i.p. injection of AG490 could increase the BNDF level from serum and brain tissue of MCAO mice (Figure 5a,b). Meanwhile, this study found the higher expression of BNDF (p < .05), neurotrophin‐3 (NT3), and also the neurotrophin receptor TrkB in the brain tissue (Figure 5c–e) in vivo. This evidence suggests that AG490 served as a pluripotent drug for neuroprotection in addition to its antiapoptotic activity. Reference: Brain Behav. 2021 Jan; 11(1): e01911. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821583/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 45.81 | 155.66 | |
| DMSO:PBS (pH 7.2) (1:10) | 0.1 | 0.34 | |
| DMF | 25.0 | 84.95 | |
| Ethanol | 7.3 | 24.8 |
The following data is based on the product molecular weight 294.3 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Ni Y, Zhang H, Zhang J, Li Z, Li Z. Inhibition of JAK2 by AG490 promotes TNF-α-induced apoptosis by inhibiting autophagy in MC3T3-E1 cells. Pharmazie. 2020 Jun 1;75(6):255-260. doi: 10.1691/ph.2020.0375. PMID: 32539921. 2. Zhou Y, Sun Y, Hou W, Ma L, Tao Y, Li D, Xu C, Bao J, Fan W. The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro. Int J Mol Med. 2020 Jul;46(1):191-200. doi: 10.3892/ijmm.2020.4592. Epub 2020 Apr 29. PMID: 32377718; PMCID: PMC7255460. 3. Fan L, Zhou L. AG490 protects cerebral ischemia/reperfusion injury via inhibiting the JAK2/3 signaling pathway. Brain Behav. 2021 Jan;11(1):e01911. doi: 10.1002/brb3.1911. Epub 2020 Oct 23. PMID: 33098244; PMCID: PMC7821583. 4. Tan G, Jiang L, Li G, Bai K. ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro. Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820948062. doi: 10.1177/1533033820948062. PMID: 33063634; PMCID: PMC7580129. |
| In vitro protocol: | 1. Ni Y, Zhang H, Zhang J, Li Z, Li Z. Inhibition of JAK2 by AG490 promotes TNF-α-induced apoptosis by inhibiting autophagy in MC3T3-E1 cells. Pharmazie. 2020 Jun 1;75(6):255-260. doi: 10.1691/ph.2020.0375. PMID: 32539921. 2. Zhou Y, Sun Y, Hou W, Ma L, Tao Y, Li D, Xu C, Bao J, Fan W. The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro. Int J Mol Med. 2020 Jul;46(1):191-200. doi: 10.3892/ijmm.2020.4592. Epub 2020 Apr 29. PMID: 32377718; PMCID: PMC7255460. |
| In vivo protocol: | 1. Fan L, Zhou L. AG490 protects cerebral ischemia/reperfusion injury via inhibiting the JAK2/3 signaling pathway. Brain Behav. 2021 Jan;11(1):e01911. doi: 10.1002/brb3.1911. Epub 2020 Oct 23. PMID: 33098244; PMCID: PMC7821583. 2. Tan G, Jiang L, Li G, Bai K. ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro. Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820948062. doi: 10.1177/1533033820948062. PMID: 33063634; PMCID: PMC7580129. |
1: DU AL, Ji TL, Yang B, Cao JF, Zhang XG, Li Y, Pan S, Zhang B, Hu ZB, Zeng XW. Neuroprotective effect of AG490 in experimental traumatic brain injury of rats. Chin Med J (Engl). 2013 Aug;126(15):2934-7. PubMed PMID: 23924471.
AG490 greatly inhibited osteoclast apoptosis. AG490 stimulated the phosphorylation of Akt and ERK. Adenovirus-mediated expression of dominant negative (DN)-Akt and DN-Ras in osteoclasts inhibited the survival of osteoclasts despite the presence of AG490. Cytochrome c release during osteoclast apoptosis was inhibited by AG490 treatment, but this effect was inhibited in the presence of LY294002 or U0126. AG490 suppressed the proapoptotic proteins Bad and Bim, which was inhibited in osteoclasts infected with DN-Akt and DN-Ras adenovirus. In addition, constitutively active MEK and myristoylated-Akt adenovirus suppressed the cleavage of pro-caspase-9 and -3 and inhibited osteoclast apoptosis induced by etoposide. Taken together, our results suggest that AG490 inhibited cytochrome c release into the cytosol at least partly by inhibiting the pro-apoptotic proteins Bad and Bim, which in turn suppressed caspase-9 and -3 activation, thereby inhibiting osteoclast apoptosis.
