Linifanib (ABT-869)

Catalog No.S1003 Synonyms: AL39324,RG3635

For research use only.

Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3.

Linifanib (ABT-869) Chemical Structure

CAS No. 796967-16-3

Selleck's Linifanib (ABT-869) has been cited by 30 publications

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Biological Activity

Description Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3.
Targets
VEGFR1/FLT1 [1]
(Cell-free assay)
CSF-1R [1]
(Cell-free assay)
VEGFR2/KDR [1]
(Cell-free assay)
FLT3 [1]
(Cell-free assay)
Kit [1]
(Cell-free assay)
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3 nM 3 nM 4 nM 4 nM 14 nM
In vitro

Linifanib shows inhibitory to Kit, PDGFRβ and Flt4 with IC50 of 14 nM, 66 nM and 190 nM in kinases assay. Linifanib also inhibits ligand-induced KDR, PDGFRβ, Kit, and CSF-1R phosphorylation with IC50 of 2 nM, 2 nM, 31 nM and 10 nM at cellular level and this cellular potency could be affected by serum protein. Linifanib suppresses VEGF-stimulated HUAEC proliferation with IC50 of 0.2 nM. While Linifanib has weak activity against tumor cells which are not induced by VEGF or PDGF, except for MV4-11 leukemia cells (with constitutively active form of Flt3) with IC50 of 4 nM. Linifanib could cause a decrease in S and G2-M phases with a corresponding increase in the sub-G0-G1 apoptotic population in MV4-11 cells. [1] Linifanib binds to the ATP-binding site of CSF-1R with Ki of 3 nM. [2] Linifanib (10 nM) exhibits a reduced phosphorylation of Akt at Ser473 and decreased phosphorylation of GSK3βat Ser9 in Ba/F3 FLT3 ITD cell lines. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse 3T3 cells M2PofGZ2dmO2aX;uJIF{e2G7 MlL4TY5pcWKrdHnvckBw\iCYRVfGMYlv\HWlZXSgbJVu[W5iS1TSJJBpd3OyaH;yfYxifGmxbjDpckBud3W|ZTCzWFMh[2WubIOgZpkhTUyLU1GsJGlEPTB;MD6wNFQh|ryP MnnrNVc{PDN|N{K=
Sf9 insect cells MU\GeY5kfGmxbjDhd5NigQ>? Mn3INVIxKG2rboO= NHTaXFhKdmirYnn0bY9vKG:oIILlZ49u[mmwYX70JGdUXC22YXfn[YQhXkWJRmKyJIV5eHKnc4Pl[EBqdiCVZkmgbY5{\WO2IHPlcIx{KGGodHXyJFEzOCCvaX7zJIJ6KEurbnHz[U1IdG9iYYPzZZktKEmFNUC9OUBvVQ>? MoS0NlE4ODh2Nki=
human MOLM13 cells MnzaR5l1d3SxeHnjbZR6KGG|c3H5 MUe3NkBp NGPRcZFEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOV0yPMUOgZ4VtdHNiaHHyZo9zcW6pIH31eIFvfCCITGSzJIFnfGW{IEeyJIhzeyCkeTDNWHMh[XO|YYmsJGdKPTB;MD6wN|ch|ryP NHj0SVYzOzZzOEewPS=>
human MV4-11 cells MW\Qdo9tcW[ncnH0bY9vKGG|c3H5 MUW3NkBp NXKzSHN4SW62aYDyc4xq\mW{YYTpc44h[WO2aY\peJkh[WejaX7zeEBHVFR|L1nUSEBp[XKkb4LpcochcHWvYX6gUXY1NTFzIHPlcIx{KGGodHXyJFczKGi{czDifUBOXFNibXX0bI9lNCCJSUWwQVAvODRizszN NV7QbXFNOjF5MEi0Olg>
human MOLT4 cells MoG1VJJwdGmoZYLheIlwdiCjc4PhfS=> M2fFUlczKGh? MmXLRY51cXC{b3zp[oVz[XSrb36gZYN1cX[rdImgZYdicW6|dDDoeY1idiCPT1zUOEBi\nSncjC3NkBpenNiYomgUXRUKG2ndHjv[EwhT0l3ME22Mlch|ryP MWOyNVcxQDR4OB?=
RS4:11 cells M{LCcnBzd2yrZnXyZZRqd25iYYPzZZk> MlnLO|IhcA>? MVrBcpRqeHKxbHnm[ZJifGmxbjDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFKVNEqxNUBk\WyuczDlfJBz\XO|aX7nJJdqdGRidInw[UBHVFR|IHHmeIVzKDd{IHjyd{BjgSCPVGOgcYV1cG:mLDDHTVUxRTlwMjFOoI0> MoT3NlE4ODh2Nki=
U937 cells M{X1RnBzd2yrZnXyZZRqd25iYYPzZZk> Ml7SO|IhcA>? NXLOWGF5SW62aYDyc4xq\mW{YYTpc44h[WO2aY\peJkh[WejaX7zeEBpfW2jbjDGUHQ{KGenbnWt[IVncWOrZX70JHU6OzdiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JG1VWyCvZYToc4QtKEeLNUC9NVkh|ryP M1\p[lIyPzB6NE[4
Assay
Methods Test Index PMID
Western blot p-PDGFRβ / PDGFRβ/ p-AKT / AKT / p-mTOR / mTOR / p-S6K ; Beclin-1 / ATG5 / ATG7 / p62 ; phospho-FLT3 / FLT3 25327881 21471285
Immunofluorescence LC3 25327881
In vivo Linifanib (0.3 mg/kg) results in complete inhibition of KDR phosphorylation in lung tissue. Linifanib also inhibits the edema response with ED50 of 0.5 mg/kg. Linifanib (7.5 and 15 mg/kg, bid) significantly inhibits both bFGF- and VEGF-induced angiogenesis in the cornea. Linifanib inhibits tumor growth in flank xenograft models including HT1080, H526, MX-1 and DLD-1 with ED75 from 4.5-12 mg/kg. Linifanib also shows efficacy in A431 and MV4-11 xenografts at low dose levels. Linifanib (12.5 mg/kg bid) reveals a decrease of microvasculure density in MDA-231 xenograft. Linifanib shows a Cmax and AUC24 hours with 0.4 μg/mL and 2.7 μg•hour/mL in HT1080 fibrosarcoma model. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Kinase assays:

    Potencies (IC50 values) are determined by assays of active kinase domains cloned and expressed in baculovirus using the FastBacbaculovirus expression system or obtained commercially. For tyrosine kinase assays, a biotinylated peptide substrate containing a single tyrosine is used with 1 mM ATP, anEu-cryptate–labeled anti-phosphotyrosine antibody (PT66), and Strepavidin-APC in a homogeneous time-resolved fluorescence assay. Serine/threonine kinases are assayed using 5 μM ATP, [33P]ATP, and a biotinylated peptide substrate with peptide capture and incorporation of 33P determined using a SA-Flashplate. Linifanib is assayed at multiple concentrations prepared by serial dilution of a DMSO stock solution of Linifanib. The concentration resulting in 50% inhibition of activity is calculated using nonlinear regression analysis of the concentration response data.

Cell Research:[1]
  • Cell lines: HUAEC, HT-29, HT1080, A431, MDA-435, MDA-231, H526, DLD-1, 9L and MV4-11 cells
  • Concentrations: 0-100 μM
  • Incubation Time: 72 hours
  • Method: Cells are seeded into 96-well plates at 2.5 × 103 per well and incubated with serum-free medium for 24 hours. Linifanib and VEGF (final, 10 ng/mL) are added and incubated for 72 hours in serum-free medium. For carcinoma cell lines, 3 × 103 cells/well are plated overnight in full growth medium. Linifanib is added to the cells in full growth medium and incubated for 72 hours. For leukemia cells, generally 5 × 104 per well are plated in full growth medium, Linifanib is added, and incubated for 72 hours. The effects on proliferation are determined by addition of Alamar Blue (final solution, 10%), incubation for 4 hours at 37 °C in a CO2 incubator and analysis in a fluorescence plate reader (544 nm, excitation: 590 nm, emission
Animal Research:[1]
  • Animal Models: 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.
  • Dosages: ~ 10 mg/kg
  • Administration: Oral administration

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5%DMSO+40%PEG 300+5%Tween80+50%ddH2O
For best results, use promptly after mixing.

10 mg/mL

Chemical Information

Molecular Weight 375.41
Formula

C21H18FN5O

CAS No. 796967-16-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC(=C(C=C1)F)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)NN=C4N

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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01401933 Completed Drug: Linifanib|Drug: Rifampin Advanced Solid Tumors Abbott May 2011 Phase 1
NCT01381341 Completed Drug: linifanib Advanced Solid Tumors Abbott May 2011 Phase 1
NCT01114191 Completed Drug: ABT-869|Drug: ketoconazole Solid Tumors Abbott May 2010 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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