| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Linifanib (formerly RG3635, ABT869, AL39324) is an orally bioavailable and ATP-competitive inhibitor of multiple kinases (e.g. VEGFR/PDGFR) with potential antitumor activity. Its IC50 values are 4 nM, 3 nM, 3 nM/4 nM, and 66 nM for KDR, CSF-1R, Flt-1/3, and PDGFRβ, respectively. Linifanib has strong antitumor efficaciousness in vivo and outstanding anti-proliferative activity in vitro.
| Targets |
Flt-1 (IC50 = 3 nM); KDR (IC50 = 4 nM); PDGFRβ (IC50 = 66 nM); FLT3 (IC50 = 4 nM); CSF-1R (IC50 = 3 nM); Kit (IC50 = 14 nM)
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| ln Vitro |
Linifanib shows inhibitory to Kit, PDGFRβ and Flt4 with IC50 of 14 nM, 66 nM and 190 nM in kinases assay. With IC50 values of 2 nM, 2 nM, 31 nM, and 10 nM at the cellular level, linifanib also prevents ligand-induced phosphorylation of KDR, PDGFRβ, Kit, and CSF-1R; the cellular potency of this inhibition may be influenced by serum protein. A 0.2 nM IC50 is used by linifanib to inhibit the proliferation of HUAECs stimulated by VEGF. Although MV4-11 leukemia cells (which have constitutively active Flt3 with an IC50 of 4 nM) are the only tumor cells against which linifanib exhibits weak activity that is not induced by VEGF or PDGF. In MV4-11 cells, linifanib may raise the sub-G0-G1 apoptotic population while causing a decrease in the S and G2-M phases. The ATP-binding site of CSF-1R is bound by linifanib, and its Ki is 3 nM. In Ba/F3 FLT3 ITD cell lines, linifanib (10 nM) showed decreased phosphorylation of GSK3β at Ser9 and reduced phosphorylation of Akt at Ser473.[3]
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| ln Vivo |
Linifanib (0.3 mg/kg) results in complete inhibition of KDR phosphorylation in lung tissue. With an ED50 of 0.5 mg/kg, linifanib also suppresses the edema response. Both bFGF- and VEGF-induced angiogenesis in the cornea are markedly inhibited by linifanib (7.5 and 15 mg/kg, bid). In flank xenograft models, linfanib (ED75, 4.5–12 mg/kg) inhibits tumor growth in HT1080, H526, MX-1, and DLD-1. Low doses of linifanib also demonstrate efficacy in A431 and MV4-11 xenografts. The MDA-231 xenograft shows a reduction in microvasculure density when treated with linifanib (12.5 mg/kg bid). AUC and Cmax of linifanib in the HT1080 fibrosarcoma model are 0.4 μg/mL and 2.7 μg•hour/mL, respectively, after 24 hours.[1]
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| Enzyme Assay |
Assays of active kinase domains that have been cloned and expressed in baculovirus using the FastBacbaculovirus expression system or that can be purchased commercially are used to determine potencies (IC50 values). In homogenous time-resolved fluorescence assays for tyrosine kinase assays, a biotinylated peptide substrate with a single tyrosine is utilized along with 1 mM ATP, an Eu-cryptate-labeled anti-phosphotyrosine antibody (PT66), and streptavidin-APC. 5 μM ATP, [33P]ATP, and a biotinylated peptide substrate with peptide capture and incorporation of 33P ascertained using an SA-Flashplate are used in the assay of serine/threonine kinases. Multiple concentrations of linifanib are analyzed by serial dilution of a linifanib stock solution in DMSO. The concentration response data is subjected to nonlinear regression analysis to determine the concentration at which 50% of activity is inhibited.
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| Cell Assay |
A 96-well plate is seeded with 2.5 × 103 cells per well, and the cells are then incubated for 24 hours in a serum-free medium. Serum-free medium is used for the 72-hour incubation period after the addition of VEGF (10 ng/mL) and linifanib. Full growth medium is plated overnight with 3 × 103 cells/well for carcinoma cell lines. Following a 72-hour incubation period, linifanib is added to the cells in their complete growth medium. Leukemia cells are typically plated at a density of 5 × 104 per well in full growth medium, followed by the addition of Linifanib and a 72-hour incubation period. When Alamar Blue (final solution, 10%), CO2 incubator, and 4 hours of 37 °C incubation are added, the effects on proliferation are measured using a fluorescence plate reader (544 nm, excitation: 590 nm, emission
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| Animal Protocol |
H526, DLD-1, MDA-231, MDA-435LM, HCT-116, H526, DLD-1, MDA-231, MDA-435LM, MV4-11 and MX-1 xenografts are established in mice.
~ 10 mg/kg Oral administration |
| References |
| Molecular Formula |
C21H18FN5O
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|---|---|
| Molecular Weight |
375.41
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| Exact Mass |
375.15
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| Elemental Analysis |
C, 67.19; H, 4.83; F, 5.06; N, 18.66; O, 4.26
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| CAS # |
796967-16-3
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| Related CAS # |
Linifanib;796967-16-3
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| Appearance |
Solid powder
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| SMILES |
CC1=CC(=C(C=C1)F)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)NN=C4N
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| InChi Key |
MPVGZUGXCQEXTM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18FN5O/c1-12-5-10-16(22)18(11-12)25-21(28)24-14-8-6-13(7-9-14)15-3-2-4-17-19(15)20(23)27-26-17/h2-11H,1H3,(H3,23,26,27)(H2,24,25,28)
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| Chemical Name |
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea
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| Synonyms |
AL39324; ABT-869; RG3635; ABT869; AL 39324; RG-3635; ABT 869; RG 3635; AL-39324
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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) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6638 mL | 13.3188 mL | 26.6375 mL | |
| 5 mM | 0.5328 mL | 2.6638 mL | 5.3275 mL | |
| 10 mM | 0.2664 mL | 1.3319 mL | 2.6638 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 |
| NCT01381341 | Completed | Drug: linifanib | Advanced Solid Tumors | Abbott | May 2011 | Phase 1 |
| NCT01401933 | Completed | Drug: Linifanib Drug: Rifampin |
Advanced Solid Tumors | Abbott | May 2011 | Phase 1 |
| NCT01413893 | Completed | Drug: linifanib | Advanced Solid Tumors | AbbVie | June 2011 | Phase 1 |
| NCT01114191 | Completed | Drug: ABT-869 Drug: ketoconazole |
Solid Tumors | Abbott | May 2010 | Phase 1 |
| NCT00733187 | Completed | Drug: ABT-869 | Advanced Solid Tumors | AbbVie | February 2009 | Phase 1 |
Linifanib inhibits phosphorylation of FLT3, AKT, and GSK3β in Ba/F3 hFLT3 ITD mutant cell lines and IL-3 rescues phosphorylation of GSK3β. Mol Cancer Ther. 2011 Jun; 10(6): 949–959. |
Linifanib prolongs survival of Ba/F3 FLT3 ITD injected mice in vivo. Mol Cancer Ther. 2011 Jun; 10(6): 949–959. |
Linifanib prolongs survival of Ba/F3 FLT3 ITD injected mice in vivo. Mol Cancer Ther. 2011 Jun;10(6):949-59. |
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