| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Other Sizes |
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.
| Targets |
Flt-1 (IC50 = 4 nM); KDR (IC50 = 20 nM); PDGFRα (IC50 = 4 nM); FGFR1 (IC50 = 2 nM)
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|---|---|
| ln Vitro |
The source of tyrosine kinase-IN-1 was compound 8K [1].
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| ln Vivo |
The PK profile of tyrosine kinase-IN-1 was reasonable (AUC(0–∞)=1.9, t1/2=4.6 h). In rats, it has a high oral bioavailability (F=63%) [1].
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| References | |
| Additional Infomation |
XL999 holds promise for patients with lung cancer and acute myeloid leukemia. XL999 is a novel compound that inhibits multiple receptor tyrosine kinases (RTKs) with pro-growth and angiogenic properties, including FGFR 1/3, PDGFRα/β, VEGFR2/KDR, KIT, and FLT3. XL999 also inhibits FLT4 and SRC. XL999 has the potential to inhibit tumor growth—both directly through its novel effects on tumor cell proliferation and indirectly through inhibition of host angiogenesis. XL999 induces cell cycle arrest through a mechanism distinct from previously known mechanisms and exhibits broad antitumor activity in xenograft models.
XL999, an FGFR/VEGFR/PDGFR/FLT3/SRC inhibitor, is a small molecule inhibitor that inhibits multiple tyrosine kinases (TKs), including fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), FMS-associated tyrosine kinase 3 (FLT3), and SRC, exhibiting potential antitumor activity. Upon administration, XL999 binds to these TKs and inhibits their activity, thereby preventing the activation of downstream signaling pathways and the proliferation of tumor cells overexpressing these TKs. FGFR, VEGFR, PDGFR, FLT-3, and SRC are upregulated in various cancer cell types and play key roles in tumor cell proliferation, angiogenesis, and metastasis. Pharmaceutical Indications Investigated for the treatment of cancer/tumor (not specified), lung cancer, and solid tumors. Mechanism of Action XL999 is a potent receptor tyrosine kinase inhibitor. These kinases are involved in tumor angiogenesis and maintenance, as well as the proliferation of certain tumor cells. It inhibits FGFR1, FGFR3, RET, VEGFR2, and PDGFR, and is also a potent inhibitor of FLT3, an important driver of leukemia cell proliferation in some acute myeloid leukemia (AML) patients. XL999 exhibits excellent activity in target-specific cell function assays. |
| Molecular Formula |
C26H28FN5O
|
|---|---|
| Molecular Weight |
445.5424
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| Exact Mass |
445.227
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| Elemental Analysis |
C, 70.09; H, 6.33; F, 4.26; N, 15.72; O, 3.59
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| CAS # |
705946-27-6
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| Related CAS # |
705946-27-6
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| PubChem CID |
10433653
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| Appearance |
Light brown to brown solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.652
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| LogP |
2.59
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
736
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2=C(C=C(NC3CCN(CC)CC3)C=C2)/C(=C(\C2=CC=CC(F)=C2)/C2NC(C)=CN=2)/C1=O
|
| InChi Key |
DMQYDVBIPXAAJA-VHXPQNKSSA-N
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| 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-
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| Chemical Name |
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)-(5-methyl-1H-imidazol-2-yl)methylidene]-1H-indol-2-one
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| Synonyms |
XL999; XL-999; XL 999
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ≥ 62.5 mg/mL (~140.3 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2445 mL | 11.2223 mL | 22.4447 mL | |
| 5 mM | 0.4489 mL | 2.2445 mL | 4.4889 mL | |
| 10 mM | 0.2244 mL | 1.1222 mL | 2.2445 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00955084 | Completed | Drug: XL999 | Advanced Malignancies | Symphony Evolution, Inc. | August 2008 | Phase 1 |
| NCT00104117 | Completed | Drug: XL999 | Cancer | Symphony Evolution, Inc. | November 2004 | Phase 1 |
| NCT00491699 | Terminated | Drug: XL999 | Non-Small-Cell Lung Cancer | Symphony Evolution, Inc. | August 2007 | Phase 1 |
| NCT00322673 | Terminated | Drug: XL999 | Acute Myeloid Leukemia AML |
Symphony Evolution, Inc. | May 2006 | Phase 2 |
| NCT00277290 | Terminated | Drug: XL999 | Ovarian Cancer | Symphony Evolution, Inc. | January 2006 | Phase 2 |
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