ホームページ Protein Tyrosine Kinase VEGFR inhibitor - c-Met inhibitor - Apoptosis related activator - Axl inhibitor Cabozantinib (XL184) For research use only.

Cabozantinib (XL184)

別名：BMS-907351

カボザンチニブ (Cabozantinib (XL184, BMS-907351)) は強力な VEGFR2 阻害剤であり、IC50 は 0.035 nM です。また c-Met, Ret, Kit, Flt-1/3/4, Tie2 および AXL に対しても阻害活性があり、cell-free assay における IC50 はそれぞれ 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM, 7 nM です。カボザンチニブは大腸がん細胞において AKT/GSK-3β/NF-κB 経路を介して PUMA 依存性アポトーシス (PUMA-dependent apoptosis) を誘発します。

Cabozantinib (XL184)化学構造

CAS No. 849217-68-1

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 33000 国内在庫あり
JPY 22000 国内在庫あり
JPY 70500 国内在庫あり
JPY 149500 国内在庫あり
JPY 295500 国内在庫あり

代表番号: 045-509-1970|電子メール：[email protected]
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製品安全説明書

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Cabozantinib (XL184)関連製品

シグナル伝達経路

VEGFR Signaling Pathways

VEGFRシグナル伝達経路

VEGFR阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
BAF3 Function assay 0.01 to 10 uM 1 hr Inhibition of TEL-fused wild type Ret (unknown origin) phosphorylation at Y1062/Y905 expressed in mouse BAF3 cells at 0.01 to 10 uM after 1 hr by Western blot analysis 26652860
BAF3 Function assay 0.01 to 10 uM 1 hr Inhibition of TEL-fused Ret S891A mutant (unknown origin) phosphorylation at Y1062/Y905 expressed in mouse BAF3 cells at 0.01 to 10 uM after 1 hr by Western blot analysis 26652860
BAF3 Function assay 0.01 to 10 uM 1 hr Inhibition of TEL-fused Ret S891A mutant (unknown origin) expressed in mouse BAF3 cells assessed as suppression of phosphorylation of PLCgamma at Y783 at 0.01 to 10 uM after 1 hr by Western blot analysis 26652860
BAF3 Function assay 0.01 to 10 uM 1 hr Inhibition of TEL-fused Ret S891A mutant (unknown origin) expressed in mouse BAF3 cells assessed as suppression of phosphorylation of Shc at Y317 at 0.01 to 10 uM after 1 hr by Western blot analysis 26652860
TT Function assay 1 to 10 uM 4 hrs Inhibition of RET C634W mutant in human TT cells assessed as suppression of PLCgamma phosphorylation at Y783 at 1 to 10 uM after 4 hrs by Western blot analysis 26652860
TT Function assay 1 to 10 uM 4 hrs Inhibition of RET C634W mutant in human TT cells assessed as suppression of ERK phosphorylation at T202/Y204 at 1 to 10 uM after 4 hrs by Western blot analysis 26652860
TT Function assay 1 to 10 uM 4 hrs Inhibition of RET C634W mutant in human TT cells assessed as suppression of AKT phosphorylation at T308/S473 at 1 to 10 uM after 4 hrs by Western blot analysis 26652860
TT Function assay 1 uM 4 hrs Inhibition of autophosphorylation of RET C634W mutant at Y1062 in human TT cells at 1 uM after 4 hrs by Western blot analysis 26652860
TT Apoptosis assay 1 uM 96 hrs Induction of apoptosis in human TT cells expressing Ret C634W mutant at 1 uM after 96 hrs by annexinV/PI staining-based flow cytometric analysis 26652860
A549 Cytotoxicity assay 10 uM 72 hrs Cytotoxicity against human A549 cells at 10 uM after 72 hrs by Incucyte live-cell imaging analysis 29407963
E98NT  Growth Inhibition Assay 0.01-10 μM IC50=89 nM 23484006
TT Function assay 1 uM Inhibition of Ret-driven oncogenic transformation of human TT cells at 1 uM by soft agar assay 26652860
BaF3 Growth inhibition assay 48 hrs Inhibition of TEL-fused Ret S891A mutant (unknown origin) expressed in mouse BaF3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.01 μM. 26652860
BA/F3 Growth inhibition assay 48 hrs Inhibition of wild type TEL-fused RET (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.05 μM. 26652860
TT Growth inhibition assay 10 days Inhibition of RET C634W mutant in human TT cells assessed as cell growth inhibition after 10 days by MTT assay, GI50 = 0.12 μM. 26652860
BA/F3 Growth inhibition assay 48 hrs Inhibition of TEL-fused Ret V804M mutant (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.89 μM. 26652860
BaF3 Growth inhibition assay 48 hrs Inhibition of TEL-fused Ret V804L mutant (unknown origin) expressed in mouse BaF3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.91 μM. 26652860
Nthy-ori 3-1 Cytotoxicity assay 10 days Cytotoxicity against human Nthy-ori 3-1 cells after 10 days by MTT assay, GI50 = 4.93 μM. 26652860
TT Function assay 4 hrs Inhibition of autophosphorylation of RET C634W mutant at Y905 in human TT cells at 1 uM after 4 hrs by Western blot analysis 26652860
PC3 Function assay 1 to 3 hrs Inhibition of c-Met phosphorylation in human PC3 cells incubated for 1 to 3 hrs, IC50 = 1.9 μM. 26717201
MDA-MB-231 Function assay 1 to 3 hrs Inhibition of AXL phosphorylation in human MDA-MB-231 cells incubated for 1 to 3 hrs, IC50 = 5 μM. 26717201
BAF3 Function assay 1 to 3 hrs Inhibition of FLT3 (unknown origin) phosphorylation transfected in mouse BAF3 cells incubated for 1 to 3 hrs, IC50 = 7.5 μM. 26717201
MDA-MB-231 Function assay 1 to 3 hrs Inhibition of KIT (unknown origin) phosphorylation transfected in human MDA-MB-231 cells incubated for 1 to 3 hrs, IC50 = 42 μM. 26717201
BA/F3 Function assay 48 hrs Inhibition of KDR (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.014 μM. 26874741
Sf21 Function assay 15 mins Inhibition of recombinant His-tagged human KDR expressed in insect Sf21 cells preincubated for 15 mins followed by substrate addition measured after 20 mins by HTRF assay, IC50 = 0.016 μM. 26874741
BA/F3 Function assay 48 hrs Inhibition of KIF5B/RET (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.19 μM. 26874741
BA/F3 Function assay 48 hrs Inhibition of KIF5B/RET (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.19 μM. 26874741
BA/F3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BA/F3 cells expressing TPR-Met after 72 hrs by CCK8 assay, IC50 = 0.0219 μM. 27068889
Sf21 Function assay 60 mins Inhibition of wild type N-terminal GST-tagged recombinant human RET (658 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA, IC50 = 0.003 μM. 27131066
Sf21 Function assay 60 mins Inhibition of N-terminal GST-tagged recombinant human RET V804M mutant (658 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA, IC50 = 0.811 μM. 27131066
BaF3 Function assay 72 hrs Inhibition of CCDC6-RET (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.889 μM. 27131066
BaF3 Function assay 72 hrs Inhibition of CCDC6-RET (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.889 μM. 27131066
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay, IC50 = 0.012 μM. 28412159
EBC1 Antiproliferative assay 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs by MTT assay, IC50 = 0.0514 μM. 28412159
H1299 Growth inhibition assay 72 hrs Growth inhibition of human H1299 cells incubated for 72 hrs by CCK8 assay, IC50 = 1.919 μM. 28651979
MCF7 Growth inhibition assay 72 hrs Growth inhibition of human MCF7 cells incubated for 72 hrs by CCK8 assay, IC50 = 2.889 μM. 28651979
A549 Growth inhibition assay 72 hrs Growth inhibition of human A549 cells incubated for 72 hrs by CCK8 assay, IC50 = 4.205 μM. 28651979
T47D Growth inhibition assay 72 hrs Growth inhibition of human T47D cells incubated for 72 hrs by CCK8 assay, IC50 = 4.448 μM. 28651979
H460 Growth inhibition assay 72 hrs Growth inhibition of human H460 cells incubated for 72 hrs by CCK8 assay, IC50 = 5.669 μM. 28651979
HuH7 Antiproliferative assay 48 hrs Antiproliferative activity against human HuH7 cells after 48 hrs by MTT assay, IC50 = 4.348 μM. 29057042
A498 Antiproliferative assay 48 hrs Antiproliferative activity against human A498 cells after 48 hrs by MTT assay, IC50 = 8.456 μM. 29057042
NCI-H727 Antiproliferative assay 48 hrs Antiproliferative activity against human NCI-H727 cells after 48 hrs by MTT assay, IC50 = 14.01 μM. 29057042
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells harboring TRP-MET after 72 hrs by CCK-8 assay, IC50 = 0.024 μM. 29146452
EBC1 Antiproliferative assay 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs by MTT assay, IC50 = 0.0048 μM. 30248654
MKN45 Antiproliferative assay 72 hrs Antiproliferative activity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.0069 μM. 30248654
SNU5 Antiproliferative assay 72 hrs Antiproliferative activity against human SNU5 cells after 72 hrs by MTT assay, IC50 = 0.0121 μM. 30248654
BAF3 Function assay 72 hrs Inhibition of TPR-tagged met (unknown origin) expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50 = 0.01986 μM. 30248654
NCI-H460 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H460 cells after 72 hrs by MTT assay, IC50 = 0.0401 μM. 30248654
MGHU3 Antiproliferative assay 72 hrs Antiproliferative activity against human MGHU3 cells after 72 hrs by CellTiter-Glo assay 30309671
RT112 Antiproliferative assay 72 hrs Antiproliferative activity against human RT112 cells after 72 hrs by CellTiter-Glo assay 30309671
MDA-MB-231 Growth Inhibition Assay IC50= 6421 nM 21926191
SNU-16 Growth Inhibition Assay IC50=1149 nM 21926191
SNU-1  Growth Inhibition Assay IC50=5223 nM 21926191
Hs746T  Growth Inhibition Assay IC50=9.9 nM 21926191
SNU-5  Growth Inhibition Assay IC50= 19 nM 21926191
U87MG Growth Inhibition Assay IC50=1851 nM 21926191
H441  Growth Inhibition Assay IC50=21700 nM 21926191
H69 Growth Inhibition Assay IC50=20200 nM 21926191
PC3 Growth Inhibition Assay IC50=10800 nM 21926191
MTC-TT Growth Inhibition Assay IC50=0.04 + 0.03 μM 21470995
MZ-CRC Growth Inhibition Assay IC50> 5 μM 21470995
TPC-1 Growth Inhibition Assay IC50=0.06 + 0.02 μM 21470995
NIH-3T3/TPR-Met Function assay Inhibition of cell proliferation in mouse NIH-3T3/TPR-Met cells, IC50 = 1 μM. 24996144
BA/F3 Growth inhibition assay Inhibition of TEL-fused VEGFR2 (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition, GI50 = 0.003 μM. 26652860
Ba/F3 Function assay Inhibition of RET (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 0.07 μM. 27814560
TT Function assay Inhibition of RET C634W mutant in human TT cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 0.26 μM. 27814560
Ba/F3 Function assay Inhibition of RET V804M mutant (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 0.74 μM. 27814560
Nthy-ori 3-1 Cytotoxicity assay Cytotoxicity against human Nthy-ori 3-1 cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 2.92 μM. 27814560
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
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生物活性

製品説明 カボザンチニブ (Cabozantinib (XL184, BMS-907351)) は強力な VEGFR2 阻害剤であり、IC50 は 0.035 nM です。また c-Met, Ret, Kit, Flt-1/3/4, Tie2 および AXL に対しても阻害活性があり、cell-free assay における IC50 はそれぞれ 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM, 7 nM です。カボザンチニブは大腸がん細胞において AKT/GSK-3β/NF-κB 経路を介して PUMA 依存性アポトーシス (PUMA-dependent apoptosis) を誘発します。
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
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]
細胞実験 細胞株 ST88-14, STS26T, and MPNST724
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 48 hours
実験の流れ

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.
実験結果図 Methods Biomarkers 結果図 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
Immunofluorescence α-tubulin 29520051
Growth inhibition assay Cell viability 23661005
In Vivo
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]
動物実験 動物モデル RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors
投与量 ~60 mg/kg
投与経路 Oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06156410 Recruiting
Ewing Sarcoma|Osteosarcoma
Children''s Hospital of Philadelphia|Children''s Hospital Colorado|Exelixis|Alex''s Lemonade Stand Foundation
 October 24 2023 Phase 1
NCT05249114 Active not recruiting
Neuroendocrine Tumors
Providence Health & Services|Exelixis|Advanced Accelerator Applications SA
 December 28 2022 Phase 1
NCT05444933 Completed
Advanced Renal Cell Carcinoma
Ipsen
 September 16 2022 --

化学情報

分子量 501.51 化学式

C28H24FN3O5
CAS No. 849217-68-1 SDF Download Cabozantinib (XL184) SDFをダウンロードする
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
保管

In vitro
Batch:

DMSO : 100 mg/mL ( (199.39 mM)； 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

mg/kg g μL 匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH2O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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