>>Signaling Pathways>> Tyrosine Kinase>> VEGFR>>Tivozanib (AV-951)

Tivozanib (AV-951)

카탈로그 번호: GC12036

티보자닙(AV-951; KRN951)은 VEGFR-1, VEGFR-2, VEGFR-3에 대해 각각 IC50α가 0.21, 0.16, 0.24 nM인 강력하고 선택적이고 경구 활성인 VEGFR 티로신 키나제 억제제이다. 티보자닙은 종양 조직에서 혈관신생 및 혈관 투과성을 억제하고 항종양 활성을 나타낸다. 티보자닙은 전이성 신세포암(RCC) 연구에 대한 잠재력이 있습니다.

Tivozanib (AV-951) 화학 구조

Size 가격 재고 수량
10mM (in 1mL DMSO)
US$64.00
재고 있음
10mg
US$62.00
재고 있음
25mg
US$88.00
재고 있음
100mg
US$230.00
재고 있음

고객 리뷰

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Sample solution is provided at 25 µL, 10mM.

Product Documents

품질 관리 및 안전 데이터 시트

현재 배치 보기

Protocol

Cell experiment [1]:

Cell lines

Human ovarian carcinoma cell lines, including A2780CP, OVCAR3 and SKOV3.

Preparation method

Soluble in DMSO >22.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10μm, 48h

Applications

Combination of tivozanib with the EGFR(Epidermal Growth Factor Receptor)-directed therapies displayed synergistic activity on cell growth inhibition and induction of apoptosis, suggesting that anti-VEGFR(vascular endothelial growth factor receptor) -targeted approaches induced sensitisation to the EGFR-directed therapies.

Clinical experiment [2]:

Diseases models

Patients with renal cell carcinoma(RCC)

Dosage form

1.5 mg OD for 3 weeks, oral administration

Application

Tivozanib exhibit an inhibitory profile with high sensitivity for inhibition of VEGFR family members. Patients receiving tivozanib had a PFS(Progression free survival) of 12.7 months – the best PFS reported in a phase III trial with mRCC.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Momeny M1, Sabourinejad Z2,3, et al, Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells. Sci Rep. 2017 Apr 6;7:45954. doi: 10.1038/srep45954.

[2]. Grünwald V1, Merseburger AS2. The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors – Is there more to come Eur J Cancer. 2013 Jul;49(11):2504-11. doi: 10.1016/j.ejca.2013.03.022. Epub 2013 Apr 16.

배경

Tivozanib is an inhibitor of tyrosine kinase with IC50 value of 160 pmol/L against VEGFR-2 [1].

Tivozanib is a quinoline-urea derivative. As a 2nd generation TKI, it has picomolar potency against VEGFR-1, -2 and -3, and minimal c-kit inhibition. Among this, Tivozanib has demonstrated a VEGFR-2 potency 2 orders of magnitude greater than sunitinib, sorafenib or pazopanib and a lower relative extent of off-target inhibition [1]. Tivozanib also shows to inhibit phosphorylation of the kinases PDGFRß and C-KIT at nanomolar level in cellular assays [2].

Tivozanib has shown antitumor activity in RCC xenograft models in addition to several other solid tumor models leading to its evaluation in clinical testing. The safety and efficacy of Tivozanib has been evaluated in several Phase I and Phase II trials. To compare the front-line use of tivozanib to sorafenib, a pivotal randomized Phase III trial has also been reported [3].

References:
[1] M.N. Fishman, S. Srinivas, R.J. Hauke, R.J. Amato, B. Esteves, M.M. Cotreau, A.L. Strahs, W.J. Slichenmyer, P. Bhargava, F.F. Kabbinavar. Phase Ib study of tivozanib (AV-951) in combination with temsirolimus in patients with renal cell carcinoma. European Journal of Cancer. 2013(49):2841-2850.
[2] Viktor Grunwald, Axel Stuart Merseburger. The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors – Is there more to come? European Journal of Cancer. 2013(49):2504-2511.
[3] C Lance Cowey. Profile of tivozanib and its potential for the treatment of advanced renal cell carcinoma. Drug Design, Development and Therapy. 2013 (7): 519-527.

화학적 특성

Cas No. 475108-18-0 SDF 아니오
동의어 해당없음
Chemical Name 1-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea
Canonical SMILES CC1=CC(=NO1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)Cl
Formula C22H19ClN4O5 M.Wt 454.86
용해도 ≥ 22.75mg/mL in DMSO Storage Store at -20°C
일반적인 팁 높은 용해도를 얻기 위해 튜브를 37℃에서 데운 후 초음파 욕조에서 잠시 흔들어 주십시오. 원액은 -20℃ 이하에서 수개월간 보관할 수 있습니다.
배송 조건 평가 샘플 솔루션: 블루아이스와 함께 배송합니다. 다른 모든 가능한 크기: 요청 시 RT 또는 블루아이스와 함께 배송합니다.

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