LY364947

LY364947 is a selective inhibitor of TGF- β type-I receptor with potential anticancer activity. LY364947 inhibits TGF- β -dependent luciferase production in mink lung cells (p3TP lux) and growth in mouse fibroblasts (NIH 3T3).

Product information

CAS Number: 396129-53-6

Molecular Weight: 272.30

Formula: C17H12N4

Chemical Name: 4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)quinoline

Smiles: C1NN=C(C=1C1=CC=NC2=CC=CC=C21)C1=CC=CC=N1

InChiKey: IBCXZJCWDGCXQT-UHFFFAOYSA-N

InChi: InChI=1S/C17H12N4/c1-2-6-15-13(5-1)12(8-10-19-15)14-11-20-21-17(14)16-7-3-4-9-18-16/h1-11H,(H,20,21)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

LY364947 is an ATP competitive and tight-binding inhibitor, inhibiting phosphorylation of P-Smad3 by TGFβR-I Kinase with Ki of 28 nM. LY364947 inhibits in vivo Smad2 phosphorylation within the NMuMg cells with IC50 of 135 nM. LY364947 reverses TGF-β-mediated growth inhibition in NMuMg cells with IC50 of 0.218 μM. LY364947 potentiates the xVent2-lux BMP4 response in NMuMg cells by 30% at concentrations as low as 0.25 μM. LY364947 (2 μM) prevents TGF-β-induced epithelial−mesenchymal transition in NMuMg cells. LY364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours. LY364947 promotes nuclear export of Foxo3a, with low Smad2/3 and high Akt phosphorylation levels in leukaemia-initiating cells. LY364947 (< 20 μM) suppresses leukaemia-initiating cells colony-forming ability after co-culture with OP-9 stromal cells.

In Vivo:

LY364947 (1 mg/kg, i.p.) accelerates lymphangiogenesis, as evidence by significantly increasing the LYVE-1-positive areas in a mouse model of chronic peritonitis. LY364947 (1 mg/kg, i.p.) significantly increases the LYVE-1-positive areas in tumor tissues in tumor xenograft models using BxPC3 pancreatic adenocarcinoma cells. LY364947 (25 mg/kg) increases p-Akt and decreases nuclear Foxo3a in leukaemia-initiating cells in CML-affected mice.

References:

1. Hayata T, Ezura Y, Asashima M, Nishinakamura R, Noda M. Dullard/Ctdnep1 Regulates Endochondral Ossification via Suppression of TGF-ß Signaling. J Bone Miner Res. 2014 Aug 22. doi: 10.1002/jbmr.2343. [Epub ahead of print] PubMed PMID: 25155999.
2. Nassar K, Grisanti S, Tura A, Lüke J, Lüke M, Soliman M, Grisanti S. A TGF-β receptor 1 inhibitor for prevention of proliferative vitreoretinopathy. Exp Eye Res. 2014 Jun;123:72-86. doi: 10.1016/j.exer.2014.04.006. Epub 2014 Apr 15. PubMed PMID: 24742493.
3. Bansal SS, Celia C, Ferrati S, Zabre E, Ferrari M, Palapattu G, Grattoni A. Validated RP-HPLC method for the simultaneous analysis of gemcitabine and LY-364947 in liposomal formulations. Curr Drug Targets. 2013 Aug;14(9):1061-9. PubMed PMID: 23721184.

Products are for research use only. Not for human use.