VatalanibVEGFR-1/-2 inhibitor,cell-permeable CAS# 212141-54-3 |
2D Structure
- Vatalanib (PTK787) 2HCl
Catalog No.:BCC1111
CAS No.:212141-51-0
- Ki8751
Catalog No.:BCC1116
CAS No.:228559-41-9
- Cediranib (AZD217)
Catalog No.:BCC1121
CAS No.:288383-20-0
- Lenvatinib (E7080)
Catalog No.:BCC1172
CAS No.:417716-92-8
- Tivozanib (AV-951)
Catalog No.:BCC1179
CAS No.:475108-18-0
Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
Cas No. | 212141-54-3 | SDF | Download SDF |
PubChem ID | 151194 | Appearance | Powder |
Formula | C20H15ClN4 | M.Wt | 346.81 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | PTK787 free base; PTK/ZK free base; CGP-79787 free base; ZK-222584 free base | ||
Solubility | DMSO : 125 mg/mL (360.43 mM; Need ultrasonic and warming) | ||
Chemical Name | N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine | ||
SMILES | C1=CC=C2C(=C1)C(=NN=C2NC3=CC=C(C=C3)Cl)CC4=CC=NC=C4 | ||
Standard InChIKey | YCOYDOIWSSHVCK-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C20H15ClN4/c21-15-5-7-16(8-6-15)23-20-18-4-2-1-3-17(18)19(24-25-20)13-14-9-11-22-12-10-14/h1-12H,13H2,(H,23,25) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Vatalanib (PTK787; ZK-222584; CGP-79787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM.In Vitro:Vatalanib also inhibits Flk, c-Kit and PDGFRβ with IC50 of 270 nM, 730 nM and 580 nM, respectively. Vatalanib shows the anti-proliferation effect by inhibiting thymidine incorporation induced by VEGF in HUVECs with and IC50 of 7.1 nM, and dose-dependently suppresses VEGF-induced survival and migration of endothelial cells in the same dose range without cytotoxic or antiproliferative effect on cells that do not express VEGF receptors[1]. A recent study shows that Vatalanib significantly inhibits the growth of hepatocellular carcinoma cells and enhances the IFN/5-FU induced apoptosis by increasing proteins levels of Bax and reduced Bcl-xL and Bcl-2[2].In Vivo:Vatalanib induces dose-dependent inhibition of the angiogenic response to VEGF and PDGF in both a growth factor implant model and a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, Vatalanib also inhibits the growth and metastasesof several human carcinomas in nude mice without significant effect on circulating blood cells or bone marrow leukocytes[1]. References: |
Vatalanib Dilution Calculator
Vatalanib Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.8834 mL | 14.4171 mL | 28.8342 mL | 57.6685 mL | 72.0856 mL |
5 mM | 0.5767 mL | 2.8834 mL | 5.7668 mL | 11.5337 mL | 14.4171 mL |
10 mM | 0.2883 mL | 1.4417 mL | 2.8834 mL | 5.7668 mL | 7.2086 mL |
50 mM | 0.0577 mL | 0.2883 mL | 0.5767 mL | 1.1534 mL | 1.4417 mL |
100 mM | 0.0288 mL | 0.1442 mL | 0.2883 mL | 0.5767 mL | 0.7209 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
Vatalanib is a novel and potent inhibitor of VEGFR with IC50 value of 77 nM, 27 nM and 37 nM for VEGFR-1 (Flt-1), VEGFR-2 (FLK-1) and VEGFR-2 (KDR), respectively [1].
The vascular endothelial growth factor receptors (VEGFRs) are tyrosine kinases and are receptors for VEGF. VEGF acts as a key factor in pathological situations that involve in pathological situations that involve enhancing vascular permeability as well as neovascularization [1].
In CHO and HUVECs cells transfected with the KDR receptor, Vatalanib inhibited the VEGF-induced phosphorylation of KDR with an IC50 of 34 nM and 17 nM for the CHO and HUVECs cells, respectively. Also, Vatalanib inhibited thymidine incorporation induced by VEGF with IC50 value of 7.1 nM in HUVECs cells. Vatalanib inhibited VEGF-induced endothelial cell proliferation in a dose-dependant way [1].
In a growth factor implant mice model, Vatalanib (12.5, 25 or 50 mg/kg, 6 days) inhibited the angiogenic response around the implant induced by VEGF and PDGF [1]. In a xenograft mouse model, treatment mice with Vatalanib through gastric tube daily caused tumor inhibition rate of 76% [2].
References:
[1]. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res, 2000, 60(8): 2178-2189.
[2]. Paesler J, Gehrke I, Gandhirajan RK, et al. The vascular endothelial growth factor receptor tyrosine kinase inhibitors vatalanib and pazopanib potently induce apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Clin Cancer Res, 2010, 16(13): 3390-3398.
- Vatalanib (PTK787) 2HCl
Catalog No.:BCC1111
CAS No.:212141-51-0
- 1,3,7-Trihydroxy-2-methoxyxanthone
Catalog No.:BCN7549
CAS No.:211948-69-5
- BIBR-1048
Catalog No.:BCC3738
CAS No.:211915-06-9
- BIBR 953 (Dabigatran, Pradaxa)
Catalog No.:BCC2139
CAS No.:211914-51-1
- Gliclazide
Catalog No.:BCC5002
CAS No.:21187-98-4
- Flumorph
Catalog No.:BCC5467
CAS No.:211867-47-9
- Nudicaucin A
Catalog No.:BCN7842
CAS No.:211815-97-3
- 2',4',5'-Trimethoxy-2'',2''-dimethylpyrano[5'',6'':6,7]isoflavone
Catalog No.:BCN1496
CAS No.:211799-56-3
- Picroside IV
Catalog No.:BCN6533
CAS No.:211567-04-3
- Nudicaucin B
Catalog No.:BCN7843
CAS No.:211557-36-7
- WHI-P180
Catalog No.:BCC3928
CAS No.:211555-08-7
- WHI-P97
Catalog No.:BCC2056
CAS No.:211555-05-4
- Apparicine
Catalog No.:BCN4008
CAS No.:2122-36-3
- 5,7-Dihydroxy-3-(4-hydroxy-3,5-dimethoxybenzyl)-6,8-dimethylchroman-4-one
Catalog No.:BCN6631
CAS No.:212201-12-2
- Ipfencarbazone
Catalog No.:BCC5465
CAS No.:212201-70-2
- Ethyl 3-(3-amino-4-(methylamino)-N-(pyridin-2-yl)benzamido)propanoate
Catalog No.:BCC8971
CAS No.:212322-56-0
- TC 2559 difumarate
Catalog No.:BCC7469
CAS No.:212332-35-9
- HS 024
Catalog No.:BCC5820
CAS No.:212370-59-7
- Oxaprozin
Catalog No.:BCC9109
CAS No.:21256-18-8
- Ebracteolatanolide A
Catalog No.:BCN3773
CAS No.:212563-72-9
- Nocistatin (human)
Catalog No.:BCC5732
CAS No.:212609-11-5
- PD 198306
Catalog No.:BCC7428
CAS No.:212631-61-3
- PD184352 (CI-1040)
Catalog No.:BCC1112
CAS No.:212631-79-3
- Xanthiazone
Catalog No.:BCN2544
CAS No.:212701-97-8
Combination of vatalanib and a 20-HETE synthesis inhibitor results in decreased tumor growth in an animal model of human glioma.[Pubmed:27022280]
Onco Targets Ther. 2016 Mar 9;9:1205-19.
BACKGROUND: Due to the hypervascular nature of glioblastoma (GBM), antiangiogenic treatments, such as Vatalanib, have been added as an adjuvant to control angiogenesis and tumor growth. However, evidence of progressive tumor growth and resistance to antiangiogenic treatment has been observed. To counter the unwanted effect of Vatalanib on GBM growth, we have added a new agent known as N-hydroxy-N'-(4-butyl-2 methylphenyl)formamidine (HET0016), which is a selective inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis. The aims of the studies were to determine 1) whether the addition of HET0016 can attenuate the unwanted effect of Vatalanib on tumor growth and 2) whether the treatment schedule would have a crucial impact on controlling GBM. METHODS: U251 human glioma cells (4x10(5)) were implanted orthotopically. Two different treatment schedules were investigated. Treatment starting on day 8 (8-21 days treatment) of the tumor implantation was to mimic treatment following detection of tumor, where tumor would have hypoxic microenvironment and well-developed neovascularization. Drug treatment starting on the same day of tumor implantation (0-21 days treatment) was to mimic cases following radiation therapy or surgery. There were four different treatment groups: vehicle, Vatalanib (oral treatment 50 mg/kg/d), HET0016 (intraperitoneal treatment 10 mg/kg/d), and combined (Vatalanib and HET0016). Following scheduled treatments, all animals underwent magnetic resonance imaging on day 22, followed by euthanasia. Brain specimens were equally divided for immunohistochemistry and protein array analysis. RESULTS: Our results demonstrated a trend that HET0016, alone or in combination with Vatalanib, is capable of controlling the tumor growth compared with that of Vatalanib alone, indicating attenuation of the unwanted effect of Vatalanib. When both Vatalanib and HET0016 were administered together on the day of the tumor implantation (0-21 days treatment), tumor volume, tumor blood volume, permeability, extravascular and extracellular space volume, tumor cell proliferation, and cell migration were decreased compared with that of the vehicle-treated group. CONCLUSION: HET0016 is capable of controlling tumor growth and migration, but these effects are dependent on the timing of drug administration. The addition of HET0016 to Vatalanib may attenuate the unwanted effect of Vatalanib.
Vatalanib sensitizes ABCB1 and ABCG2-overexpressing multidrug resistant colon cancer cells to chemotherapy under hypoxia.[Pubmed:26206183]
Biochem Pharmacol. 2015 Sep 1;97(1):27-37.
Cancer microenvironment is characterized by significantly lower oxygen concentration. This hypoxic condition is known to reduce drug responsiveness to cancer chemotherapy via multiple mechanisms, among which the upregulation of the ATP-binding cassette (ABC) efflux transporters confers resistance to a wide variety of structurally unrelated anticancer drugs. Vatalanib (PTK787/ZK22584) is a multitargeted tyrosine kinase inhibitor for all isoforms of VEGFR, PDGFR and c-Kit, which exhibit potent anticancer activity in vitro and in vivo. We investigated the potentiation effect of Vatalanib on the anticancer activity of conventional cytotoxic drugs in colon cancer cell lines under both normoxic and hypoxic conditions. Mechanistically, Vatalanib was found to inhibit ABCG2 and ABCB1 efflux activity, presumably by acting as a competitive inhibitor and interfering with their ATPase activity. Under hypoxic growth condition, ABCG2 and ABCB1-overexpressing cells sorted out by FACS technique as side population (SP) were found to be significantly more responsive to SN-38 (ABCG2 and ABCB1 substrate anticancer drug) in the presence of Vatalanib. The anchorage independent soft agar colony formation capacity of the SP cells was remarkably reduced upon treatment with a combination of SN-38 and Vatalanib, compared to SN-38 alone. However, Vatalanib, at concentrations that produced the circumvention of the transporters-mediated resistance, did not appreciably alter ABCG2/ABCB1 mRNA or protein expression levels or the phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2). Our study thus advocates the further investigation of Vatalanib for use in combination chemotherapy to eradicate drug-resistant cancer cells under hypoxia.
2D and 3D similarity landscape analysis identifies PARP as a novel off-target for the drug Vatalanib.[Pubmed:26403354]
BMC Bioinformatics. 2015 Sep 24;16:308.
BACKGROUND: Searching for two-dimensional (2D) structural similarities is a useful tool to identify new active compounds in drug-discovery programs. However, as 2D similarity measures neglect important structural and functional features, similarity by 2D might be underestimated. In the present study, we used combined 2D and three-dimensional (3D) similarity comparisons to reveal possible new functions and/or side-effects of known bioactive compounds. RESULTS: We utilised more than 10,000 compounds from the SuperTarget database with known inhibition values for twelve different anti-cancer targets. We performed all-against-all comparisons resulting in 2D similarity landscapes. Among the regions with low 2D similarity scores are inhibitors of vascular endothelial growth factor receptor (VEGFR) and inhibitors of poly ADP-ribose polymerase (PARP). To demonstrate that 3D landscape comparison can identify similarities, which are untraceable in 2D similarity comparisons, we analysed this region in more detail. This 3D analysis showed the unexpected structural similarity between inhibitors of VEGFR and inhibitors of PARP. Among the VEGFR inhibitors that show similarities to PARP inhibitors was Vatalanib, an oral "multi-targeted" small molecule protein kinase inhibitor being studied in phase-III clinical trials in cancer therapy. An in silico docking simulation and an in vitro HT universal colorimetric PARP assay confirmed that the VEGFR inhibitor Vatalanib exhibits off-target activity as a PARP inhibitor, broadening its mode of action. CONCLUSION: In contrast to the 2D-similarity search, the 3D-similarity landscape comparison identifies new functions and side effects of the known VEGFR inhibitor Vatalanib.
Data showing the circumvention of oxaliplatin resistance by vatalanib in colon cancer.[Pubmed:27014726]
Data Brief. 2016 Mar 2;7:437-44.
We have recently reported that Vatalanib, an orally active small molecule multi-tyrosine kinase inhibitor (Hess-Stumpp et al., 2005 [1]), can sensitize multidrug resistant (MDR) colon cancer cells to chemotherapy under hypoxia by inhibiting two MDR transporters ABCB1 and ABCG2 (To et al., 2015 [2]). This data article describes the possible circumvention of resistance to specifically platinum (Pt)-based anticancer drugs by Vatalanib via inhibition of two other efflux transporters ABCC2 and ATP7A. Data from the flow cytometric transporter efflux assay showed specific inhibition of ABCC2 activity by Vatalanib in stable transfected cells and ABCC2-overexpressing oxaliplatin-resistant colon cancer cells HCT116/Oxa. We also performed the transporter ABCC2 ATPase assay and showed an increase in ATP hydrolysis by ABCC2 in the presence of Vatalanib. ATP7A mRNA expression was also shown to be upregulated in HCT116/Oxa cells. Vatalanib was shown to suppress this upregulated ATP7A expression. Data from the cellular Pt accumulation assay showed a lower Pt accumulation in HCT116/Oxa cells than the parental sensitive HCT116 cells. Vatalanib was shown to increase cellular Pt accumulation in a concentration-dependent manner. Combination of oxaliplatin and Vatalanib was shown to restore the suppressed apoptosis in HCT116/Oxa cells.