WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205665
Description: XL999, a Spectrum Selective Kinase Inhibitor(TM) (SSKIs), is a potent inhibitor of key RTKs implicated in the development and maintenance of tumor vasculature and in the proliferation of some tumor cells. It inhibits the FGFR, VEGFR and PDGFR RTKs and exhibited excellent activity in target-specific cellular functional assays. In addition, XL999 is a potent inhibitor of FLT3, an important driver of leukemia cell proliferation in some patients with acute myelogenous leukemia (AML). In several preclinical models of human tumors, including breast, lung, colon and prostate cancer, XL999 demonstrated potent inhibition of tumor growth, and also caused regression of large well-established tumors.
MedKoo Cat#: 205665
Chemical Formula: C26H28FN5O
Exact Mass: 445.2278
Molecular Weight: 445.5424
Elemental Analysis: C, 70.09; H, 6.33; F, 4.26; N, 15.72; O, 3.59
Synonym: XL999, XL-999, XL 999
IUPAC/Chemical Name: (Z)-5-((1-ethylpiperidin-4-yl)amino)-3-((3-fluorophenyl)(5-methyl-1H-imidazol-2-yl)methylene)indolin-2-one
InChi Key: DMQYDVBIPXAAJA-VHXPQNKSSA-N
InChi Code: InChI=1S/C26H28FN5O/c1-3-32-11-9-19(10-12-32)30-20-7-8-22-21(14-20)24(26(33)31-22)23(25-28-15-16(2)29-25)17-5-4-6-18(27)13-17/h4-8,13-15,19,30H,3,9-12H2,1-2H3,(H,28,29)(H,31,33)/b24-23-
SMILES Code: O=C1NC2=C(C=C(NC3CCN(CC)CC3)C=C2)/C1=C(C4=CC=CC(F)=C4)/C5=NC=C(C)N5
XL999 is a potent spectrum-selective inhibitor of receptor tyrosine kinases including VEGFR2/KDR, FGFR1/3, PDGFR-ÃŸ, FLT3, RET, KIT, & SRC. A Ph 1 clinical study in pts w/advanced malignancies evaluating weight-based (0.2 - 6.4 mg/kg) & fixed dose (200 mg & 160 mg) XL999 administered by 4hr IV infusion on a wkly or every other wk schedule has shown preliminary evidence of anti-tumor activity (3 PRs & 10 pts w/SD lasting 3-26+ months). The safety profile was characterized by hypertension & cardiovascular changes including EKG, LVEF decrease &/or cardiac enzyme elevation following 1st dose administration. DLTs were cardiac failure & transaminase elevation. A dose of 2.4 mg/kg/wk was selected for phase II evaluation. （source : Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 18112 ).
1: You WK, Sennino B, Williamson CW, Falcón B, Hashizume H, Yao LC, Aftab DT, McDonald DM. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res. 2011 Jul 15;71(14):4758-68. doi: 10.1158/0008-5472.CAN-10-2527. Epub 2011 May 25. PubMed PMID: 21613405; PubMed Central PMCID: PMC3138890.
2: Bayes M. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):153-73. PubMed PMID: 17440629.