Cabozantinib (BMS-907351)

Catalog No.S1119 Synonyms: XL184

For research use only.

Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway.

Cabozantinib (BMS-907351) Chemical Structure

CAS No. 849217-68-1

Selleck's Cabozantinib (BMS-907351) has been cited by 124 publications

Purity & Quality Control

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Biological Activity

Description Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway.
Targets
VEGFR2/KDR [1]
(Cell-free assay)
c-Met [1]
(Cell-free assay)
Axl [1]
(Cell-free assay)
0.035 nM 1.3 nM 7 nM
In vitro

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [1] XL184 at low concentration (0.1-0.5 μM) is sufficient to induce marked inhibition of constitutive and inducible Met phosphorylation and its resultant downstream signaling in MPNST cells, and inhibit HGF-induced MPNST cell migration and invasion. XL184 also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although XL-184 has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
E98NT  NEDvXopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHpNE4xOS1zMDFOwG0> Ml;QSG1UVw>? NYDlUnk5UUN3ME24PUBvVQ>? MnrHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OESwNFYoRjJ|NEi0NFA3RC:jPh?=
SNU-5  MmrjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4rwcGlEPTB;IEG5JI5O M37YTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUK2NVkyLz5{MUmyOlE6OTxxYU6=
Hs746T  NF3yUmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mlm3TWM2OD17Lkmgcm0> MkX3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7Mk[xPVEoRjJzOUK2NVkyRC:jPh?=
SNU-1  MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDsTWM2OD13MkKzJI5O NWPVW3A{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5NlYyQTFpPkKxPVI3OTlzPD;hQi=>
SNU-16 NHmwco1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzV[mFCUUN3ME2xNVQ6KG6P MnHHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7Mk[xPVEoRjJzOUK2NVkyRC:jPh?=
MDA-MB-231 MkX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjHTWM2OD1iNkSyNUBvVQ>? NIC2PJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUmyOlE6OSd-MkG5NlYyQTF:L3G+
U87MG M2LWV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvKNXlKSzVyPUG4OVEhdk1? MkLQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7Mk[xPVEoRjJzOUK2NVkyRC:jPh?=
H441  M2n1SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVnJR|UxRTJzN{CwJI5O NIW2Voo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUmyOlE6OSd-MkG5NlYyQTF:L3G+
H69 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTJyMkCwJI5O M3nwT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUK2NVkyLz5{MUmyOlE6OTxxYU6=
PC3 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlP4TWM2OD1zMEiwNEBvVQ>? MlfKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7Mk[xPVEoRjJzOUK2NVkyRC:jPh?=
MTC-TT MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1P0NWlEPTB;MD6wOEAsKDBwMEOg{txO MmfwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF2N{C5PVUoRjJzNEewPVk2RC:jPh?=
MZ-CRC NHTjVmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonxTWM2OD5iNTFOwG0> NH3oRmc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS3NFk6PSd-MkG0O|A6QTV:L3G+
TPC-1 M4C3fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorHTWM2OD1yLkC2JEshOC5yMjFOwG0> NGjlVGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS3NFk6PSd-MkG0O|A6QTV:L3G+
NIH-3T3/TPR-Met M3;tXmZ2dmO2aX;uJIF{e2G7 M1HGeGlvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:wIHnuJI1wfXOnIF7JTE0{XDNxVGDSMW1mfCClZXzsd{whUUN3MDC9JFEh|ryPLh?= NFvhUnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEm5OlE1PCd-MkS5PVYyPDR:L3G+
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BaF3 NHPMdVNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYDEVIoyPDhiaILz M2LsPWlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIGLleEBUQDlzQTDteZRidnRiKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gcY92e2ViQnHGN{Bk\WyuczDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFfJOVAhRSByLkCxJO69VS5? NFfKVZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Nk[1Nlg3OCd-Mk[2OVI5PjB:L3G+
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TT M1nY[Gdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MljvNVAh\GG7cx?= NHPG[4FKdmirYnn0bY9vKG:oIGLFWEBEPjN2VzDteZRidnRiaX6gbJVu[W5iVGSgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkAyOCCmYYnzJIJ6KE2WVDDhd5NigSxiR1m1NEA:KDBwMUKg{txONg>? MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjZ3Mki2NEc,OjZ4NUK4OlA9N2F-
BA/F3 NGfscVZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NIDaS2E1QCCqcoO= MmrjTY5pcWKrdHnvckBw\iCWRVyt[pV{\WRiUnX0JHY5ODSPIH31eIFvfCBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDtc5V{\SCEQT;GN{Bk\WyuczDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFfJOVAhRSByLki5JO69VS5? NV2xUo9CRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[2OVI5PjBpPkK2OlUzQDZyPD;hQi=>
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Nthy-ori 3-1 MWPDfZRwfG:6aXPpeJkh[XO|YYm= MnvTNVAh\GG7cx?= MWDDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDOeIh6NW:{aTCzMVEh[2WubIOgZYZ1\XJiMUCg[IF6eyCkeTDNWHQh[XO|YYmsJGdKPTBiPTC0Mlk{KM7:TT6= MnLGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ4NUK4OlAoRjJ4NkWyPFYxRC:jPh?=
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Assay
Methods Test Index PMID
Western blot p-MET(Y1234/1235) / MET / p-EGFR(Y1068) / EGFR / p-Gab1(Y627) / Gab1 / p-AKT(S473) / p-ERK / p-EIF4E ; p-MET / p-ERK / p-AKT 29188469 29520051
Immunofluorescence α-tubulin 29520051
Growth inhibition assay Cell viability 23661005
In vivo XL184 treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumors disrupts 83% of the tumor vasculature, reduces pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and extensive tumor cell apoptosis, and slows regrowth of the tumor vasculature after drug withdrawal, more significantly compared with XL999 that blocks VEGFR but not c-Met, leading to only 43% reduction in vascularity, suggesting that concurrent inhibition of VEGFR and other functionally relevant receptor tyrosine kinases (RTK) amplifies angiogenesis inhibition. XL184 also decreases invasiveness of primary tumors and reduces metastasis. [1] XL184 at 30 mg/kg/day significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. [2] Administration of XL184 induces dose-dependent inhibition of tumor growth in breast, lung, and glioma tumor models, in association with decreased tumor and endothelial cell proliferation as well as increased apoptosis. A single oral dose of XL184 is sufficient to induce sustained tumor growth inhibition in MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats at 100 mg/kg and 10 mg/kg, respectively. [3]

Protocol (from reference)

Cell Research:

[2]

  • Cell lines: ST88-14, STS26T, and MPNST724
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 48 hours
  • Method:

    Cells are exposed to various concentrations of XL184 for 48 hours. Cell growth is determined by MTS assays using CellTiter96 Aqueous Non-Radioactive Cell Proliferation Assay kit. Absorbance is measured at a wavelength of 490 nm, and the absorbance values of treated cells are presented as a percentage of the absorbance of untreated cells.

Animal Research:

[1]

  • Animal Models: RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors
  • Dosages: ~60 mg/kg
  • Administration: Oral gavage

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

5mg/mL

Chemical Information

Molecular Weight 501.51
Formula

C28H24FN3O5

CAS No. 849217-68-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05249114 Not yet recruiting Drug: Cabozantinib|Drug: Lu-177 Neuroendocrine Tumors Providence Health & Services|Exelixis|Advanced Accelerator Applications SA December 1 2022 Phase 1
NCT05048212 Not yet recruiting Drug: Nivolumab|Drug: Ipilimumab|Drug: Cabozantinib Brain Metastases|Renal Cell Carcinoma M.D. Anderson Cancer Center|Exelixis|Bristol-Myers Squibb September 30 2022 Phase 2
NCT05444933 Not yet recruiting -- Advanced Renal Cell Carcinoma Ipsen July 15 2022 --
NCT05361434 Not yet recruiting -- Advanced Renal Cell Carcinoma Ipsen July 2022 --

(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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