TYRPHOSTIN AG 879 Property

Boiling point:

432.7±55.0 °C(Predicted)

Density 

1.127±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Sealed in dry,Store in freezer, under -20°C

solubility 

DMSO: at 26 mg/mlsoluble

form 

Orange-yellow solid

pka

9.63±0.70(Predicted)

color 

Yellow

Stability:

Stable for 1 year as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.

Safety

WGK Germany 

3

HS Code 

29309090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H312Harmful in contact with skin

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P322Specific measures (see …on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P363Wash contaminated clothing before reuse.

P501Dispose of contents/container to..…

TYRPHOSTIN AG 879 Chemical Properties,Usage,Production

Description

AG-879 (148741-30-4) inhibits NGF-induced neurite growth in PC12 cells via selective inhibition of NGF receptor(pp140c-trk) autophosphorylation (IC50 = 10 μM). No inhibition of EGF, or PDGF receptor phosphorylation is observed at typical working concentrations.

Uses

Tyrphostin AG 879 is a dual EGFR/HER2 inhibitor that was administered together with androgen withdrawal therapy and was shown to sensitize prostate cancer cells to apoptosis.

Definition

ChEBI: 3-amino-2-[(3,5-ditert-butyl-4-oxo-1-cyclohexa-2,5-dienylidene)methyl]-3-mercapto-2-propenenitrile is a monoterpenoid.

in vitro

ag 879 has been widely used as a tyr kinase inhibitor specific for erbb2 and flk-1, a vegf receptor. the ic50 value for erbb2 and flk-1 was approximately 1 μm. ag 879 at 10 nm blocked the specific interaction between the tyr-kinase etk and pak1 (a cdc42/rac-dependent ser/thr kinase) in cell culture. ag 879 (10 nm) showed no inhibitory effects on the purified etk and pak1 directly in vitro, suggesting that this drug blocked the etk-pak1 pathway by targeting the highly sensitive kinase upstream of etk. src was insensitive to ag 879. fak was inhibited by 100 nm ag 879, but not by 10 nm ag879 [2]. ag 879 inhibited proliferation of human breast cancer cells through an effect involving inhibition of map kinase activation. ag 879 markedly inhibited the expression of the raf-1 gene, which encoded an upstream mapkkk. additionally, ag 879 inhibited the expression of her-2[3]. treatment with ag879 (20 μm) dramatically decreased proliferation with a variable increase in apoptosis in cell lines from human leiomyosarcoma (htb-114, htb-115, htb-88), rhabdomyosarcoma (htb-82, te-671), prostatic adenocarcinoma (pc-3), acute promyelocytic leukemia (hl-60) and histiocytic lymphoma (u-937) [4].

in vivo

in athymic nod/scid mice grafted with htb-114 or hl-60, administration of ag879 at 2 mg induced a decrease in cancer growth [4]. ag 879 administration (20 mg/kg) kept 50% of mice absolutely free of ras-induced sarcomas. in the nude mice carrying v-ha-ras transformed nih 3t3 cells, ag 879 dramatically reduced the size of the growing sarcomas [5].

References

1) Ohmichi et al. (1993), The tyrosine kinase inhibitor tyrphostin blocks the cellular actions of nerve growth factor; Biochemistry, 32 4650