LY2801653 Property

Boiling point:

795.3±60.0 °C(Predicted)

Density 

1.42±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

≥27.65 mg/mL in DMSO; insoluble in H2O; ≥5.02 mg/mL in EtOH with gentle warming and ultrasonic

form 

solid

pka

10.83±0.70(Predicted)

InChI

InChI=1S/C30H22F2N6O3/c1-17-3-9-23(30(40)38(17)22-7-4-20(31)5-8-22)29(39)36-21-6-10-27(25(32)12-21)41-28-11-18-16-35-37(2)26(18)13-24(28)19-14-33-34-15-19/h3-16H,1-2H3,(H,33,34)(H,36,39)

InChIKey

QHADVLVFMKEIIP-UHFFFAOYSA-N

SMILES

C1(=O)N(C2=CC=C(F)C=C2)C(C)=CC=C1C(NC1=CC=C(OC2C(C3=CNN=C3)=CC3=C(C=2)C=NN3C)C(F)=C1)=O

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H351Suspected of causing cancer

H360May damage fertility or the unborn child

H372Causes damage to organs through prolonged or repeated exposure

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe 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.

P281Use personal protective equipment as required.

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

P308+P313IF exposed or concerned: Get medical advice/attention.

P314Get medical advice/attention if you feel unwell.

P330Rinse mouth.

P405Store locked up.

P501Dispose of contents/container to..…

LY2801653 Chemical Properties,Usage,Production

Description

LY2801653 is an orally bioavailable MET kinase inhibitor (K_i = 2 nM). It also inhibits MST1R, Axl, MNK1/2, FLT3, DDR1, and DDR2 (IC₅₀s = 11, 2, 7, 7, 0.1, and 7 nM, respectively, in a cell-based assay). It inhibits MET autophosphorylation stimulated by hepatocyte growth factor (HGF) in H460 and S114 cells (IC₅₀s = 35.2 and 59.2 nM, respectively) and inhibits growth of Ba/F3 cells transfected with MET-activating mutations (IC₅₀s = 12-248 nM). LY2801653 (0.01-10 μM) completely blocks cell scattering induced by HGF in DU145 cells. It reduces tumor growth in MET autocrine (U-87MG) and MET over-expression (H441) mouse xenograft models when administered at doses of 4 and 12 mg/kg.

Description

MET is a tyrosine kinase that leads to downstream activation of several pathways including RAS and MAPK.?As a result, it is quite possible that MET inhibition can be active in RAS mutant tumors and maybe associated with EGFR resistance in NSCLC.?Two MET inhibitors, tivantinib and onartuzumab, have been examined in KRAS mutant NSCLC with others in clinical trials at this time.

Clinical Use

Preclinical testing also has shown merestinib to inhibit several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, and NTRK1/2/3.

target

c-MET

References

[1] yan s b et al. , ly2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against met, mst1r, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. invest new drugs. 2012, 31: 833-844.