Dovitinib - CAS 405169-16-6
Catalog number: B0084-091881
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C21H21FN6O
Molecular Weight:
392.429
COA:
Inquire
Targets:
c-Kit | VEGFR
Description:
Dovitinib (TKI258) potently inhibited FLT3, c-KIT, FGFR, VEGFR1/2/3, PDGFRß and CSF-1R with IC50 values of 1, 2, 5, 10, 8, 27, 36 nM respectively. Dovitinib selectively blocked the growth of wild-type (WT) or activated mutant FGFR3-transformed B9 cells and human myeloma cell lines. Dovitinib was an effective treatment in a xenograft mouse model of FGFR3 multiple myeloma.
Synonyms:
Dovitinib, TKI258; TKI 258;TKI-258; CHIR 265; CHIR265; CHIR-265; RAF-265; RAF 265; RAF265.
MSDS:
Inquire
Current Developer:
Novartis International AG.
1.Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells.
Chon HJ1, Lee Y1, Bae KJ1, Byun BJ2, Kim SA3, Kim J4. Amino Acids. 2016 Mar 19. [Epub ahead of print]
Traf2- and Nck-interacting kinase (TNIK) is a member of the germinal center kinase family. TNIK was first identified as a kinase that is involved in regulating cytoskeletal organization in many types of cells, and it was recently proposed as a novel therapeutic target in several types of human cancers. Although previous studies suggest that TNIK plays a pivotal role in cancer cell survival and prognosis, its function in hematological cancer cell survival has not been investigated. Here we investigated the relationship between TNIK function and cell viability in multiple myeloma IM-9 cells using TNIK small interfering RNA (siRNA) transfection and dovitinib treatment. Treatment of IM-9 cells with TNIK siRNA and dovitinib treatment reduced cell proliferation. The ATP competing kinase assay and western blot analysis showed that dovitinib strongly inhibited both the interaction of TNIK with ATP (K i, 13 nM) and the activation of Wnt signaling effectors such as β-catenin and TCF4.
2.Randomized, Open-Label Phase 2 Study Comparing Frontline Dovitinib vs Sorafenib in Patients With Advanced Hepatocellular Carcinoma.
Cheng AL1, Thongprasert S2, Lim HY3, Sukeepaisarnjaroen W4, Yang TS5, Wu CC6, Chao Y7, Chan SL8, Kudo M9, Ikeda M10, Kang YK11, Pan H12, Numata K13, Han G14, Balsara B15, Zhang Y15, Rodriguez AM16, Zhang Y15, Wang Y15, Poon RT17. Hepatology. 2016 Apr 15. doi: 10.1002/hep.28600. [Epub ahead of print]
Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on/2 days off; n = 82) vs sorafenib (400 mg, twice daily; n = 83) was evaluated in an open-label, randomized phase 2 study of Asian-Pacific patients with advanced HCC. Primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) per local investigator, respectively. Eligible patients had progressed after or were ineligible for surgical and/or locoregional therapies. Median OS (95% CI) was 8.0 (6.6-9.1) months for dovitinib and 8.4 (5.4-11.3) months for sorafenib.
3.Eruptive milia and comedones during treatment with dovitinib.
Kimes K1, Beasley K, Dalton SR. Dermatol Online J. 2015 Sep 17;21(9). pii: 13030/qt8kw141mb.
Dovitinib (TKI258) is a multi-targeted receptor tyrosine kinase inhibitor currently under clinical trials for a wide variety of cancers. Well-known side effects include nausea, vomiting, diarrhea, and fatigue. To date, there have only been only two reported cases with skin manifestations as a side effect. We report a case of eruptive facial milia and comedones in the setting of dovitinib treatment for metastatic gastrointestinal cancer. This case is unique as the clinical presentation was more rapid in onset and showed an absence of inflammatory lesions. Although the pathogenesis for skin manifestations is presently unknown, we present this case to increase awareness of potentially under-reported cutaneous side effects.
4.Monitoring vascular normalization induced by antiangiogenic treatment with 18F-fluoromisonidazole-PET.
Hernández-Agudo E1, Mondejar T1, Soto-Montenegro ML2, Megías D3, Mouron S1, Sanchez J1, Hidalgo M4, Lopez-Casas PP4, Mulero F5, Desco M6, Quintela-Fandino M7. Mol Oncol. 2015 Dec 22. pii: S1574-7891(15)00247-1. doi: 10.1016/j.molonc.2015.12.011. [Epub ahead of print]
BACKGROUND: Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with 18F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related c-Kit Products


CAS 656247-17-5 Nintedanib

Nintedanib
(CAS: 656247-17-5)

Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59...

CAS 875337-44-3 MGCD-265

MGCD-265
(CAS: 875337-44-3)

MGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively and also inhibits Ron a...

CAS 635702-64-6 Pazopanib HCl

Pazopanib HCl
(CAS: 635702-64-6)

Pazopanib is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 1...

CAS 326914-10-7 SU11652

SU11652
(CAS: 326914-10-7)

SU11652 is a cell-permeable and sunitinib-like inhibitor of tyrosine kinase receptor (RTK) and angiogenesis with antineoplastic property. It selectively inhibit...

CAS 152459-95-5 Imatinib

Imatinib
(CAS: 152459-95-5)

Imatinib inhibits the SLF-dependent activation of wild-type c-kit kinase activity with a IC50 for these effects of approximately 0.1 μM, which is similar to the...

CAS 857876-30-3 Motesanib Diphosphate

Motesanib Diphosphate
(CAS: 857876-30-3)

Motesanib Diphosphate is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; similar activity against Kit, ~10-fold more...

CAS 883986-34-3 AZD2932

AZD2932
(CAS: 883986-34-3)

AZD2932 is a new quinazoline ether inhibitor and is a high affinity inhibitor of VEFGR-2 and PDGFR. It has a balanced ~1:1 ratio of activity vs both VEGFR-2 an...

CAS 796967-16-3 Linifanib

Linifanib
(CAS: 796967-16-3)

Description of Linifanib: Linifanib is an orally bioavailable, small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. L...

Chemical Structure

CAS 405169-16-6 Dovitinib

Quick Inquiry

Verification code

Featured Items