Home Protein Tyrosine Kinase VEGFR inhibitor Cabozantinib (XL184)

연구용

Cabozantinib (XL184) Met/VEGFR2 inhibitor

제품 번호S1119

A potent VEGFR2 inhibitor with IC50 of 0.035 nM, Cabozantinib (XL184) 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. It induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway.
Cabozantinib (XL184) VEGFR inhibitor Chemical Structure

화학 구조

분자량: 501.51

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품질 관리 (Quality Control)

배치: 순도: 99.99%
99.99

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
E98NT  Growth Inhibition Assay 0.01-10 μM DMSO IC50=89 nM 23484006
SNU-5  Growth Inhibition Assay IC50= 19 nM 21926191
Hs746T  Growth Inhibition Assay IC50=9.9 nM 21926191
SNU-1  Growth Inhibition Assay IC50=5223 nM 21926191
SNU-16 Growth Inhibition Assay IC50=1149 nM 21926191
MDA-MB-231 Growth Inhibition Assay IC50= 6421 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
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
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
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
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 Inhibition of Ret-driven oncogenic transformation of human TT cells at 1 uM by soft agar assay 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
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
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
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
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
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
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
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 501.51 화학식

C28H24FN3O5

 보관 (수령일로부터)
CAS 번호 849217-68-1 SDF 다운로드 원액 보관

동의어 BMS-907351 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

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (199.39 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
VEGFR2/KDR
(Cell-free assay)
0.035 nM
c-Met
(Cell-free assay)
1.3 nM
Axl
(Cell-free assay)
7 nM
시험관 내(In vitro)
Cabozantinib (XL184) has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectively, and has low activity against FGFR1 with IC50 of 5.294 μM. At low concentration (0.1-0.5 μM), it 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. This compound also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although it has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth.
생체 내(In vivo)
Cabozantinib (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. This compound also decreases invasiveness of primary tumors and reduces metastasis. At 30 mg/kg/day, it significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. 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 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.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-MET / p-ERK / p-AKT p-MET(Y1234/1235) / MET / p-EGFR(Y1068) / EGFR / p-Gab1(Y627) / Gab1 / p-AKT(S473) / p-ERK / p-EIF4E
S1119-WB2
29520051
Immunofluorescence α-tubulin
S1119-IF1
29520051
Growth inhibition assay Cell viability
S1119-viability
23661005

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
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 --