Su-11274

Su-11274 is a selective Met tyrosine kinase inhibitor with IC50 of 10 nM. Su-11274 increases tumorigenicity and enriched for melanoma-initiating cells by bioenergetic modulation. Su-11274 suppresses proliferation and motility of pancreatic cancer cells. Su-11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation. Su-11274 exhibits a selective inhibition pattern toward different receptor mutated variants.

Product information

CAS Number: 658084-23-2

Molecular Weight: 568.09

Formula: C28H30ClN5O4S

Synonym:

SU 11274

SU11274

SU-11274

Chemical Name: (3Z)-N-(3-Chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1H-pyrrol-2-yl]methylene]-2,3-dihydro-N-methyl-2-oxo-1H-indole-5-sulfonamide

Smiles: CN1CCN(CC1)C(=O)C1C(C)=C(/C=C2/C3=CC(=CC=C3NC/2=O)S(=O)(=O)N(C)C2=CC(Cl)=CC=C2)NC=1C

InChiKey: FPYJSJDOHRDAMT-KQWNVCNZSA-N

InChi: InChI=1S/C28H30ClN5O4S/c1-17-25(30-18(2)26(17)28(36)34-12-10-32(3)11-13-34)16-23-22-15-21(8-9-24(22)31-27(23)35)39(37,38)33(4)20-7-5-6-19(29)14-20/h5-9,14-16,30H,10-13H2,1-4H3,(H,31,35)/b23-16-

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: ≥12 months 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:

Su-11274 exhibits greater than 50-fold selectivity for Met versus Flk and more than 500 times selectivity versus other tyrosine kinases such as FGFR-1, c-src, PDGFbR, and EGFR. Su-11274 inhibits the phosphorylation of key regulators of the PI3K pathway, including AKT, FKHR, or GSK3β. Su-11274 treatment inhibits the growth of TPR-MET-transformed BaF3 cells in a dose-dependent manner with IC50 of < 3 μM in the absence of interleukin 3, without growth inhibition of BaF3 cells transformed by other oncogenic tyrosine kinases, including BCR-ABL, TEL-JAK2, TEL-ABL, and TEL-PDGFβR. In addition to cell growth, Su-11274 treatment significantly inhibits the migration of BaF3. TPR-MET cells by 44.8% and 80% at 1 μM and 5 μM, respectively. Su-11274 inhibits HGF-dependent phosphorylation of Met as well as HGF-dependent cell proliferation and motility with an IC50 of 1-1.5 μM. In H69 and H345 cells which have functional Met receptor, Su-11274 inhibits the HGF-induced cell growth with IC50 of 3.4 μM and 6.5 μM, respectively. Su-11274 induces G1 cell cycle arrest with cells in G1 phase increased from 42.4% to 70.6% at 5 μM, and induces caspase-dependent apoptosis by 24% at 1 μM. Su-11274 inhibits cell viability in c-Met-expressing non-small cell lung cancer (NSCLC) cells with IC50 values of 0.8-4.4 μM, and abrogates hepatocyte growth factor-induced phosphorylation of c-Met and its downstream signaling.

References:

1. Kucerova L, Demkova L, Skolekova S, Bohovic R, Matuskova M. Tyrosine kinase inhibitor SU11274 increased tumorigenicity and enriched for melanoma-initiating cells by bioenergetic modulation. BMC Cancer. 2016 May 12;16:308. doi: 10.1186/s12885-016-2341-y. PubMed PMID: 27175734; PubMed Central PMCID: PMC4866285.
2. Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N. SU11274 suppresses proliferation and motility of pancreatic cancer cells. Oncol Lett. 2015 Sep;10(3):1468-1472. Epub 2015 Jul 2. PubMed PMID: 26622692; PubMed Central PMCID: PMC4533741.
3. Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N. Co-culture of hepatocellular carcinoma cells and human umbilical endothelial cells damaged by SU11274. Biomed Rep. 2014 Nov;2(6):799-803. Epub 2014 Sep 10. PubMed PMID: 25279148; PubMed Central PMCID: PMC4179721.
4. Gao SH, Liu C, Wei J, Feng Y. Effect of c-Met inhibitor SU11274 on human colon cancer cell growth. Chin Med J (Engl). 2013 Jul;126(14):2705-9. PubMed PMID: 23876900.
5. Gao W, Bing X, Li M, Yang Z, Li Y, Chen H. Study of critical role of c-Met and its inhibitor SU11274 in colorectal carcinoma. Med Oncol. 2013 Jun;30(2):546. doi: 10.1007/s12032-013-0546-3. Epub 2013 Mar 28. PubMed PMID: 23536000.

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