LY364947

Cas：396129-53-6

Product Information：

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).

Chemical Formula: C17H12N4

Exact Mass: 272.1062

Molecular Weight: 272.3

Elemental Analysis: C, 74.98; H, 4.44; N, 20.58

Chemical Name:

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

InChi Key:

IBCXZJCWDGCXQT-UHFFFAOYSA-N

InChi Code: 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)

Smiles Code:

C1(C2=CNN=C2C3=NC=CC=C3)=CC=NC4=CC=CC=C14

Technical Data：

Appearance: Light yellow 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: >2 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

In Vitro：

LY-364947 is an ATP competitive and tight-binding inhibitor, inhibiting phosphorylation of P-Smad3 by TGFβR-I Kinase with Ki of 28 nM. LY-364947 inhibits in vivo Smad2 phosphorylation within the NMuMg cells with IC50 of 135 nM. LY-364947 reverses TGF-β-mediated growth inhibition in NMuMg cells with IC50 of 0.218 μM. LY-364947 potentiates the xVent2-lux BMP4 response in NMuMg cells by 30% at concentrations as low as 0.25 μM. LY-364947 (2 μM) prevents TGF-β-induced epithelial−mesenchymal transition in NMuMg cells[1]. LY-364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours. LY-364947 promotes nuclear export of Foxo3a, with low Smad2/3 and high Akt phosphorylation levels in leukaemia-initiating cells. LY-364947 (< 20 μM) suppresses leukaemia-initiating cells colony-forming ability after co-culture with OP-9 stromal cells.

In Vivo：

LY-364947 (1 mg/kg, i.p.) accelerates lymphangiogenesis, as evidence by significantly increasing the LYVE-1-positive areas in a mouse model of chronic peritonitis. LY-364947 (1 mg/kg, i.p.) significantly increases the LYVE-1-positive areas in tumor tissues in tumor xenograft models using BxPC3 pancreatic adenocarcinoma cells[2]. LY-364947 (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. Jaskova K, Pavlovicova M, Cagalinec M, Lacinova L, Jurkovicova D. TGFβ1 downregulates neurite outgrowth, expression of Ca2+ transporters, and mitochondrial dynamics of in vitro cerebellar granule cells. Neuroreport. 2014 Mar 26;25(5):340-6. doi: 10.1097/WNR.0000000000000106. PubMed PMID: 24535220.

4. 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.

5. van Beuge MM, Prakash J, Lacombe M, Post E, Reker-Smit C, Beljaars L, Poelstra K. Enhanced effectivity of an ALK5-inhibitor after cell-specific delivery to hepatic stellate cells in mice with liver injury. PLoS One. 2013;8(2):e56442. doi: 10.1371/journal.pone.0056442. Epub 2013 Feb 18. PubMed PMID: 23441194; PubMed Central PMCID: PMC3575413.

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