Linifanib (ABT-869)

Catalog No.S1003 Synonyms: AL39324,RG3635

Linifanib (ABT-869) Chemical Structure

Molecular Weight(MW): 375.41

Linifanib (ABT-869) 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). Phase 3.

Size Price Stock Quantity  
In DMSO USD 180 In stock
USD 120 In stock
USD 210 In stock
USD 570 In stock
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3 Customer Reviews

  • Effect of the anti-vascular agents Linifanib (100 nM) in the VMO(vascularized micro-organ). VMOs were exposed to the drug at day 5 and cultured for an additional 96 h.

    Sci Rep, 2016, 6:31589.. Linifanib (ABT-869) purchased from Selleck.

    (B and C) KMCH-1 cells were plated alone (monoculture) or together with PDGF-BB-secreting LX-2 cells (co-culture) in a transwell insert co-culture system (KMCH-1 cells in the bottom wells and LX-2 cells in the inserts; 1:1 ratio) for 2 days. Cells were treated as indicated with vehicle, rhTRAIL (10 ng/ml for 6 h on day 2), rhTRAIL plus imatinib [rhTRAIL:10 ng/ml for 6 h on day 2; Imatinib: 5 μmol/L for 24 h (day2)], or rhTRAIL plus linifanib [rhTRAIL: 10 ng/ml for 6 h on day 2; Linifanib:0.5 μmol/L for 24 h (day2)]. After rhTRAIL treatment for 6 h,KMCH-1 cells were analysed for apoptotic nuclear morphology by DAPI-staining (B) and for DNA fragmentation by transferasemediated dUTP nick end labelling assay (C) with quantification of apoptotic nuclei by fluorescence microscopy.

    Liver Int 2011 32, 400-409. Linifanib (ABT-869) purchased from Selleck.

  • T47D breast cancer cells were pretreated with indicated concentrations of ABT-869

     

     

    Dr. Zhang of Tianjin Medical University. Linifanib (ABT-869) purchased from Selleck.

Purity & Quality Control

Choose Selective VEGFR Inhibitors

Biological Activity

Description Linifanib (ABT-869) 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). 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)
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 M4jB[GZ2dmO2aX;uJIF{e2G7 MlLPTY5pcWKrdHnvckBw\iCYRVfGMYlv\HWlZXSgbJVu[W5iS1TSJJBpd3OyaH;yfYxifGmxbjDpckBud3W|ZTCzWFMh[2WubIOgZpkhTUyLU1GsJGlEPTB;MD6wNFQh|ryP MWCxO|M1OzN5Mh?=
Sf9 insect cells MV;GeY5kfGmxbjDhd5NigQ>? M1zkNlEzOCCvaX7z MULJcohq[mm2aX;uJI9nKHKnY3;tZolv[W62IFfTWE11[WepZXSgWmVITlJ{IHX4dJJme3OnZDDpckBU\jliaX7z[YN1KGOnbHzzJIFnfGW{IEGyNEBucW6|IHL5JGtqdmG|ZT3HcI8h[XO|YYmsJGlEPTB;NTDuUS=> MWOyNVcxQDR4OB?=
human MOLM13 cells M4PzemN6fG:2b4jpZ4l1gSCjc4PhfS=> NH7PW2E4OiCq MkniR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUW9NVTF|IHPlcIx{KGijcnLvdolv\yCvdYThcpQhTkyWMzDh[pRmeiB5MjDodpMh[nliTWTTJIF{e2G7LDDHTVUxRTBwMEO3JO69VQ>? M13qdFI{PjF6N{C5
human MV4-11 cells M3fnVXBzd2yrZnXyZZRqd25iYYPzZZk> NHTvU5E4OiCq MVfBcpRqeHKxbHnm[ZJifGmxbjDhZ5Rqfmm2eTDh[4FqdnO2IF\MWFMwUVSGIHjhdoJwemmwZzDoeY1idiCPVkStNVEh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UV{Bu\XSqb3SsJGdKPTB;MD6wOEDPxE1? MVqyNVcxQDR4OB?=
human MOLT4 cells MlL5VJJwdGmoZYLheIlwdiCjc4PhfS=> MYm3NkBp NUHvdnIxSW62aYDyc4xq\mW{YYTpc44h[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNU2xVPCCjZoTldkA4OiCqcoOgZpkhVVSVIH3leIhw\CxiR1m1NF03NjdizszN NYLrNpVrOjF5MEi0Olg>
RS4:11 cells MmThVJJwdGmoZYLheIlwdiCjc4PhfS=> NEDQZ3I4OiCq NWXmZ|VbSW62aYDyc4xq\mW{YYTpc44h[WO2aY\peJkh[WejaX7zeEBpfW2jbjDSV|Q7OTFiY3XscJMh\XiycnXzd4lv\yC5aXzkJJR6eGViRlzUN{Bi\nSncjC3NkBpenNiYomgUXRUKG2ndHjv[EwhT0l3ME25MlIh|pyv NWrSPXU2OjF5MEi0Olg>
U937 cells Mny3VJJwdGmoZYLheIlwdiCjc4PhfS=> NFzhWlI4OiCq MV\BcpRqeHKxbHnm[ZJifGmxbjDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE[OVEOg[4Vv\S2mZX\pZ4lmdnRiVUmzO{Bk\WyuczDh[pRmeiB5MjDodpMh[nliTWTTJI1mfGixZDygS2k2OD1zOTFOwG0> Ml\FNlE4ODh2Nki=

... Click to View More Cell Line Experimental Data

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

Kinase Assay:[1]
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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]
+ Expand
  • 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
    (Only for Reference)
Animal Research:[1]
+ Expand
  • 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.
  • Formulation: 2% ethanol, 5% Tween 80, 20% PEG400, 73% saline
  • Dosages: ~ 10 mg/kg
  • Administration: Oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 75 mg/mL (199.78 mM)
Water slightly soluble or insoluble
Ethanol slightly soluble or insoluble
In vivo Add solvents individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 375.41
Formula

C21H18FN5O

CAS No. 796967-16-3
Storage powder
in solvent
Synonyms AL39324,RG3635

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01506934 Terminated Advanced or Metastatic Solid Tumors Abbott October 2011 Phase 1
NCT01286974 Terminated Advanced Solid Tumors Abbott August 2011 Phase 1
NCT01413893 Completed Advanced Solid Tumors Abbott June 2011 Phase 1
NCT01365910 Terminated Recurrent Colon Cancer|Recurrent Rectal Cancer|Stage IVA Colon Cancer|Stage IVA Rectal Cancer|Stage IVB Colon Cancer|Stage IVB Rectal Cancer Vanderbilt-Ingram Cancer Center June 2011 Phase 2
NCT01381341 Completed Advanced Solid Tumors Abbott May 2011 Phase 1
NCT01401933 Completed Advanced Solid Tumors Abbott May 2011 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID