SKLB-610

SKLB-610 is a VEGFR inhibitor that potently suppresses human tumor angiogenesis. SKLB-610 inhibited angiogenesis-related tyrosine kinase VEGFR2, fibroblast growth factor receptor 2 (FGFR2) and platelet-derived growth factor receptor (PDGFR) at rate of 97%, 65% and 55%, respectively, at concentration of 10μM in biochemical kinase assays. SKLB-610 exhibited its antitumor activity as a multi-targeted inhibitor with more potent inhibition of VEGFR2 activity. Its potential to be a candidate of anticancer agent is worth being further investigated.

Product information

CAS Number: 1125780-41-7

Molecular Weight: 415.37

Formula: C21H16F3N3O3

Synonym:

SKLB 610

SKLB610

SKLB-610

Chemical Name: N-methyl-4-(4-(3-(trifluoromethyl)benzamido)phenoxy)picolinamide

Smiles: CNC(=O)C1=CC(=CC=N1)OC1C=CC(=CC=1)NC(=O)C1=CC(=CC=C1)C(F)(F)F

InChiKey: WACDHHMEVMSODJ-UHFFFAOYSA-N

InChi: InChI=1S/C21H16F3N3O3/c1-25-20(29)18-12-17(9-10-26-18)30-16-7-5-15(6-8-16)27-19(28)13-3-2-4-14(11-13)21(22,23)24/h2-12H,1H3,(H,25,29)(H,27,28)

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:

SKLB-610 has a selective inhibition of VEGF-induced proliferation with an IC50 value of 2.2μM. In HUVECs, SKLB-610 shows selectivity of 2-fold for inhibition of VEGF-induced proliferation versus bFGF-induced proliferation with an IC50 value of 4.7μM. In HUVECs, SKLB-610 blocks VEGF stimulated phosphorylation of VEGFR2 in a dose dependent manner after SKLB-610 treatment. SKLB-610 significant inhibits HUVECs capillary tube formation in a concentration-dependent manner. SKLB-610 inhibits the formation of vessel-like structures at 2.5 μM.

In Vivo:

SKLB-610 inhibits tumor xenograft model growth of human non-smallcell lung cancer model (A549) and human colon cancer model (HCT116) and is well tolerated. After 30 days treatment, SKLB-610 exhibited a significantly antitumor activity in inhibiting tumor progress compared with control. The inhibition rate of tumor volume in SKLB-610-treated groups is 70.2% (50 mg/kg) for A549 and 77.1% (50 mg/kg) for HCT116 . The retention times of SKLB-610 and the internal standard are 5.6 and 8.1 min, respectively. The quantification limit is 67 ng/mL. The calibration curves are linear over a concentration range of 0.1–50 µg/mL.

References:

1. Huang Y, Luo X, You X, Xia Y, Song X, Yu L. The preparation and evaluation of water-soluble SKLB610 nanosuspensions with improved bioavailability. AAPS PharmSciTech. 2013 Sep;14(3):1236-43. doi: 10.1208/s12249-013-0005-7. Epub 2013 Aug 10. PubMed PMID: 23934433; PubMed Central PMCID: PMC3755164.
2. Luo X, Li S, Xie Y, He J, Li J, Lin H, Wang N, Yang S, Zhao Y, Yu L, Song X. Pharmacokinetic studies of a novel multikinase inhibitor for treating cancer by HPLC-UV. J Chromatogr Sci. 2013 Jan;51(1):17-20. doi: 10.1093/chromsci/bms098. Epub 2012 Jun 17. PubMed PMID: 22710664.
3. Cao ZX, Zheng RL, Lin HJ, Luo SD, Zhou Y, Xu YZ, Zeng XX, Wang Z, Zhou LN, Mao YQ, Yang L, Wei YQ, Yu LT, Yang SY, Zhao YL. SKLB610: a novel potential inhibitor of vascular endothelial growth factor receptor tyrosine kinases inhibits angiogenesis and tumor growth in vivo. Cell Physiol Biochem. 2011;27(5):565-74. doi: 10.1159/000329978. Epub 2011 Jun 15. PubMed PMID: 21691074.

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