Tyrphostin 8

Names

[ Name ]:
Tyrphostin 8

[Synonym ]:
4-(HYDROXYBENZYLIDENE)-MALONONITRILE
4-Hydroxybenzylidenemalononitrile
(4-Hydroxybenzylidene)malonitrile
EINECS 223-253-0
2-[(4-hydroxyphenyl)methylidene]propanedinitrile
MFCD00020189

Biological Activity

[Description]:

Tyrphostin 8 is a tyrosine kinase, with an IC50 of 560 μM for EGFR kinase. Tyrphostin 8 is also a GTPase inhibitor. Tyrphostin 8 can inhibit the protein serine/threonine phosphatase calcineurin (IC50=21 μM)[1][2][3].

[Related Catalog]:

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Signaling Pathways >> GPCR/G Protein >> Ras

Research Areas >> Metabolic Disease

[Target]

EGFR:560 μM (IC50)

calcineuin phosphatase:21 μM (IC50)

[In Vitro]

Tyrphostin 8 (10-100 μM; pretreated for 20 min) blocks the Carbachol-initiated PKCδ tyrosine phosphorylation and ERK1/2 activation in parotid acinar cells[1]. Tyrphostin 8 (10-100 μM) produces a rapid and large increase in the basal O2 consumption of parotid acinar[1]. Tyrphostin 8 (10-100 μM) reduces the parotid ATP content by ∼90% at the concentration of 100 μM[1]. Tyrphostin 8 increases apical-to-basolateral transport of insulin-transferrin conjugate by enhancing transferrin receptor-mediated transcytosis in filter-grown Caco-2 cell monolayer[2]. Western Blot Analysis[1] Cell Line: Parotid acinar cells Concentration: 10, 100 μM Incubation Time: Pretreated for 20 min Result: Reduced the increase in tyrosine phosphorylation of PKCδ initiated by carbachol. Reduced the activation of ERK1/2 by carbachol.

[In Vivo]

Tyrphostin 8 improves the glucose-lowering effect of Insulin-transferrin in Streptozotocin-induced diabetic rats[2].

[References]

[1]. Soltoff SP. Evidence that tyrphostins AG10 and AG18 are mitochondrial uncouplers that alter phosphorylation-dependent cell signaling. J Biol Chem. 2004 Mar 19;279(12):10910-8.

[2]. Xia CQ, et, al. Tyrphostin-8 enhances transferrin receptor-mediated transcytosis in Caco-2- cells and inreases hypoglycemic effect of orally administered insulin-transferrin conjugate in diabetic rats. Pharm Res. 2001 Feb;18(2):191-5.

[3]. Martin BL. Inhibition of calcineurin by the tyrphostin class of tyrosine kinase inhibitors. Biochem Pharmacol. 1998 Aug 15;56(4):483-8.

Chemical & Physical Properties

[ Density]:
1.29 g/cm3

[ Boiling Point ]:
354.3ºC at 760 mmHg

[ Melting Point ]:
186-189 °C

[ Molecular Formula ]:
C₁₀H₆N₂O

[ Molecular Weight ]:
170.17

[ Flash Point ]:
168.1ºC

[ Exact Mass ]:
170.04800

[ PSA ]:
67.81000

[ LogP ]:
1.82276

[ Index of Refraction ]:
1.653

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
ethanol: 20 mg/mL, clear

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: OO4200000

CHEMICAL NAME :: Malononitrile, (p-hydroxybenzylidene)-

CAS REGISTRY NUMBER :: 3785-90-8

BEILSTEIN REFERENCE NO. :: 2209079

LAST UPDATED :: 199612

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C10-H6-N2-O

MOLECULAR WEIGHT :: 170.18

WISWESSER LINE NOTATION :: QR D1UYCN&CN

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 14,1325,1965

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 65 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 228,1315,1970

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H319

[ Precautionary Statements ]:
P301 + P310-P305 + P351 + P338

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ Hazard Codes ]:
T: Toxic;

[ Risk Phrases ]:
25

[ Safety Phrases ]:
S45

[ RIDADR ]:
UN 2811 6.1/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
OO4200000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1

[ HS Code ]:
2926909090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2926909090

[ Summary ]:
HS:2926909090 other nitrile-function compounds VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:30.0%

Articles

Effect of combined changes in delayed extraction time and potential gradient on the mass resolution and ion discrimination in the analysis of polydisperse polymers and polymer blends by delayed extraction matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Rapid Commun. Mass Spectrom. 13(24) , 2511-7, (1999)

Data reported here show that, in the delayed extraction matrix-assisted laser desorption/ionization time-of-flight (DE-MALDI-TOF) mass spectrometric analysis of synthetic polydisperse polymers, differ...

[Prevalence of Aeromonas spp. pediatric gastroenteritis].

CMAJ 138(8) , 714-7, (1988)

A selective medium and biochemical tests were used to search for Aeromonas spp. in the stools of 536 children, more than 90% of whom had "gastroenteritis", seen at Sainte-Justine Hospital, Montreal, i...

Characterization and modulation of the transferrin receptor on brain capillary endothelial cells.

Pharm. Res. 21(5) , 761-9, (2004)

The expression level of the transferrin receptor (TfR) on brain capillary endothelial cells (BCECs) and the endocytosis of 125I-transferrin (125I-Tf) by this receptor was investigated. Furthermore, th...