Synonym
SKLB610; SKLB 610; SKLB-610.
IUPAC/Chemical Name
N-methyl-4-(4-(3-(trifluoromethyl)benzamido)phenoxy)picolinamide
InChi Key
WACDHHMEVMSODJ-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(NC)C1=NC=CC(OC2=CC=C(NC(C3=CC=CC(C(F)(F)F)=C3)=O)C=C2)=C1
Appearance
white 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, DMF, and ethanol
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
Biological target:
SKLB610 demonstrates potent inhibition of VEGFR2, FGFR2, and PDGFRβ activity at 10 µM, with inhibitions of 97%, 65%, and 55%, respectively. It exhibits selectivity for these targets over PI3K, EGFR, Aurora A, Cdk2/cyclin E, and Cdk6/cyclin D3 at the same concentration. In HUVECs, SKLB610 inhibits VEGFR2 phosphorylation induced by VEGF, hinders HUVEC proliferation induced by VEGF and bFGF (IC50s = 2.2 and 4.7 µM, respectively), and impedes capillary tube formation and migration at concentrations of 2.5 and 10 µM, respectively. Additionally, SKLB610 shows anti-proliferative effects on various cancer cells (IC50s = 5.7, 5.3, 25.6, 6.4, and 6.3 µM for A549, HCT116, MDA-MB-231, Raji, and DU145 cells, respectively).
In vitro activity:
SKLB610 has potential to overcome resistance to cytotoxic anticancer drugs, which could benefit patients with multidrug-resistant cancers. Neither ABCB1 nor ABCG2 confered resistance to SKLB610, but SKLB610 selectively sensitized ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic anticancer agents. SKLB610 reversed ABCG2-mediated MDR by attenuating the drug-efflux function of ABCG2 without affecting its total cell expression.
Reference: Biomed Pharmacother. 2022 May;149:112922. https://pubmed.ncbi.nlm.nih.gov/36068781/
In vivo activity:
SKLB610 exhibited antitumor activity and has potential to be a candidate of anticancer agent. Chronic intraperitoneally administration of SKLB610 resulted in significant inhibition in the growth of established human A549 and HCT116 tumor xenografts in nude mice without exhibiting toxicity. Histological analysis showed significant reductions in intratumoral microvessel density of 43-55% relative to controls depending on the specific tumor xenografts.
Reference: Cell Physiol Biochem. 2011;27(5):565-74. https://pubmed.ncbi.nlm.nih.gov/21691074/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
20.0 |
48.15 |
| DMSO |
16.0 |
38.52 |
| Ethanol |
5.0 |
12.04 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
415.37
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Wu CP, Murakami M, Wu YS, Lin CL, Li YQ, Huang YH, Hung TH, Ambudkar SV. The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs. Biomed Pharmacother. 2022 May;149:112922. doi: 10.1016/j.biopha.2022.112922. Epub 2022 Apr 5. PMID: 36068781; PMCID: PMC10506422.
2. 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. PMID: 21691074.
In vitro protocol:
1. Wu CP, Murakami M, Wu YS, Lin CL, Li YQ, Huang YH, Hung TH, Ambudkar SV. The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs. Biomed Pharmacother. 2022 May;149:112922. doi: 10.1016/j.biopha.2022.112922. Epub 2022 Apr 5. PMID: 36068781; PMCID: PMC10506422.
In vivo protocol:
1. 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. PMID: 21691074.
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.
