Vatalanib (PTK787) 2HCl

Catalog No.S1101
5 5 9 Product Citations

Vatalanib (PTK787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM, less potent against VEGFR1/Flt-1, 18-fold against VEGFR3/Flt-4. Phase 3.

Price Stock Quantity  
In DMSO USD 64 In stock
USD 70 In stock
USD 210 In stock
USD 370 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Vatalanib (PTK787) 2HCl Chemical Structure

Vatalanib (PTK787) 2HCl Chemical Structure
Molecular Weight: 419.73

Validation & Quality Control

Customer Reviews(3)

Quality Control & MSDS

Related Compound Libraries

VEGFR Inhibitors with Unique Features

  • Pan VEGFR Inhibitor

    Regorafenib (BAY 73-4506) Pan-VEGFR inhibitor, VEGFR1/VEGFR2/VEGFR3, IC50=13 nM/4.2 nM/46 nM.

  • Most Potent VEGFR Inhibitor

    Axitinib VEGFR1, VEGFR2, VEGFR3, IC50=0.1 nM, 0.2 nM, 0.1-0.3 nM.

  • FDA-approved Inhibitor

    Axitinib Approved by FDA for Renal Cell Carcinoma.

  • Classic VEGFR Inhibitor

    Dovitinib (TKI-258, CHIR-258) Multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM.

Product Information

  • Compare VEGFR Inhibitors
    Compare VEGFR Products
  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description Vatalanib (PTK787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM, less potent against VEGFR1/Flt-1, 18-fold against VEGFR3/Flt-4. Phase 3.
Targets VEGFR2/KDR [1] VEGFR1/FLT1 [1] VEGFR2/Flk1 [1] PDGFRβ [1] VEGFR3/FLT4 [1]

   View More

IC50 37 nM 77 nM 270 nM 580 nM 660 nM
In vitro Vatalanib also inhibits Flk, c-Kit and PDGFRβ with IC50 of 270 nM, 730 nM and 580 nM, respectively. Furthermore, 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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

VEGF Receptor Tyrosine Kinase Assays The in vitro kinase assays are performed in 96-well plates as a filter binding assay, using the recombinant GST-fused kinase domains expressed in baculovirus and purified over glutathione-Sepharose. γ-[33P]ATP is used as the phosphate donor, and poly-(Glu:Tyr 4:1) peptide is used as the acceptor. Recombinant GST-fusion proteins are diluted in 20 mM Tris·HCl (pH 7.5) containing 1–3 mM MnCl2, 3–10 mM MgCl2, 0.25 mg/mL polyethylene glycol 20000, and 1 mM DTT, according to their specific activity. Each GST-fused kinase is incubated under optimized buffer conditions [20 mM Tris-HCl buffer (pH 7.5), 1–3 mM MnCl2, 3–10 mM MgCl2, 3–8 μg/mL poly-(Glu:Tyr 4:1), 0.25 mg/mL polyethylene glycol 20000, 8 μM ATP, 10 μM sodium vanadate, 1 mM DTT, and 0.2 μCi[γ-33P]ATP in a total volume of 30 μL in the presence or absence of a test substance for 10 minutes at ambient temperature. The reaction is stopped by adding 10 μL of 250 mM EDTA. Using a 96-well filter system, half the volume (20 μL) is transferred onto a Immobilon-polyvinylidene difluoride membrane. The membrane is then washed extensively in 0.5% H3PO4 and then soaked in ethanol. After drying, Microscint cocktail is added, and scintillation counting is performed. IC50s for PTK787/ZK 222584 or SU5416 in these as well as all assays described below are calculated by linear regression analysis of the percentage inhibition.

Cell Assay: [1]

Cell lines HUVECs
Concentrations 0-10 μM
Incubation Time 48 hours
Method As a test of the ability of PTK787/ZK 222584 to inhibit a functional response to VEGF, an endothelial cell proliferation assay, based on BrdUrd incorporation is used. Subconfluent HUVECs are seeded into 96-well plates coated with 1.5% gelatin and then incubated at 37 °C and 5% CO2 in growth medium. After 24 hours, growth medium is replaced by basal medium containing 1.5% FCS and a constant concentration of VEGF (50 ng/mL), bFGF (0.5 ng/mL), or FCS (5%), in the presence or absence of PTK787/ZK 222584. As a control, wells without growth factor are also included. After 24 hours of incubation, BrdUrd labeling solution is added, and cells incubated an additional 24 hours before fixation, blocking, and addition of peroxidase-labeled anti-BrdUrd antibody. Bound antibody is then detected using 3,3′5,5′-tetramethylbenzidine substrate, which results in a colored reaction product that is quantified spectrophotometrically at 450 nm.

Animal Study: [1]

Animal Models A431 epithelial carcinoma, Ls174T colon carcinoma, HT-29 colon carcinoma, PC-3 prostate carcinoma, DU145 prostate carcinoma, and CWR-22 prostate carcinoma cells are injected s.c. into the nude mice.
Formulation Vatalanib is dissolved in distilled water containing 5% DMSO and 1% Tween 80.
Dosages 25-100 mg/kg
Administration Administered via p.o.
Solubility 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Wood JM, et al. Cancer Res. 2000, 60(8), 2178-2189.

[2] Murakami M, et al. Ann Surg Oncol. 2011, 18(2), 589-596.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-10-24)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT00390000 Suspended Unspecified Adult Solid Tumor, Protocol Specific Mayo Clinic|National Cancer Institute (NCI) January 2007 Phase 1
NCT00627198 Completed Neuroendocrine Tumors University of Iowa|Novartis Pharmaceuticals December 2006 Phase 2
NCT00615160 Suspended Melanoma University of Schleswig-Holstein December 2006 Phase 1|Phase 2
NCT00385853 Completed Glioblastoma Massachusetts General Hospital|Dana-Farber Cancer Institu  ...more Massachusetts General Hospital|Dana-Farber Cancer Institute|Novartis September 2006 Phase 1
NCT00348790 Active, not recruiting Brain and Central Nervous System Tumors|Sarcoma Northwestern University|Novartis May 2006 Phase 2

view more

Chemical Information

Download Vatalanib (PTK787) 2HCl SDF
Molecular Weight (MW) 419.73
Formula

C20H15ClN4.2HCl

CAS No. 212141-51-0
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms ZK 222584 2HCl
Solubility (25°C) * In vitro DMSO 85 mg/mL (202 mM)
Water 10 mg/mL (23 mM)
Ethanol 6 mg/mL (14 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine dihydrochloride

Research Area

Customer Reviews (3)


Click to enlarge
Rating
Source Cell Res 2011 21, 1080-1087. Vatalanib (PTK787) 2HCl purchased from Selleck
Method Microangiography
Cell Lines embryos
Concentrations 30 μM
Incubation Time
Results Both of these inhibitors (PTK787 or ZM323881), when individually combined with Dasatinib or U0126, induced a reduction of vessel lumen size. However, they did not lead to this phenotype when added alone.

Click to enlarge
Rating
Source Circ Res 2011 108, 1190-1198. Vatalanib (PTK787) 2HCl purchased from Selleck
Method Immunofluorescence
Cell Lines HUVECs
Concentrations 10 nmol/L
Incubation Time
Results The multikinase inhibitors sorafenib and vatalanib potently suppressed VEGF-evoked Ca2+ rises (Figure a). HUVECs were transfected with eYFP-tagged STIM1 which showed the expected 14 microtubule-like localization pattern (Figure b). VEGF caused marked clustering of eYFP-STIM1 (Figure c). Additional experiments were carried out where endogenous STIM1 was knocked down by RNA interference (Figure d). STIM1 siRNA suppressed VEGF-evoked Ca2+ signals (Figure d).

Click to enlarge
Rating
Source Development 2013 140, 4323-34. Vatalanib (PTK787) 2HCl purchased from Selleck
Method Histochemical
Cell Lines Breeding tubercles
Concentrations 500 nM
Incubation Time 6-14 days
Results Tg(KR21; fli1a:EGFP) females were treated with T (1 μg/l) and PTK787 (500 nM), an inhibitor of vascular endothelial growth factor receptor tyrosine kinases that effectively inhibits regenerative angiogenesis in the zebrafish caudal fin. Immediately following pectoral fin amputation, PTK787 treatments were initiated. Females were treated for 2 days with PTK787 prior to T treatment to ensure that PTK787 had time to take effect. At 6 dpa, a single row of BTs is observed on PTK787/T-treated female intact fins and the stump of regenerating pectoral fins. No BTs are visible in the regenerate (Aa-Ca). At 8 dpa, BTs on the intact fin have grown slightly and isolated BTs are observed on PTK787/T-treated fin regenerates (Ea,Fa). At 14 dpa, a small BT cluster has formed in the proximal PTK787/T-treated fin regenerate (Ga,Ha). Finally, all PTK787 treatments, including PTK787/T treatments, efficiently inhibit neo-angiogenesis in the intact and regenerating pectoral fins, limiting the distance of tissue regeneration (Aa-Ja, Ac-Jc). Control females that received PTK787 alone or system water did not form BTs (Hc,d,Ic,d).

Product Citations (9)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related VEGFR Products

  • SKLB1002

    SKLB1002 is a potent and ATP-competitive VEGFR2 inhibitor with IC50 of 32 nM.

  • AZD9291

    AZD9291 is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR, respectively. Phase 3.

  • CO-1686 (AVL-301)

    CO-1686 is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT, respectively. Phase 2.

  • Cabozantinib (XL184, BMS-907351)

    Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and 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, respectively.

  • Regorafenib (BAY 73-4506)

    Regorafenib (BAY 73-4506) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.

  • Nintedanib (BIBF 1120)

    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 nM/65 nM. Phase 3.

  • Axitinib

    Axitinib is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.

    Features:Superior as second-line therapy relative to sorafenib (current standard-of-care).

  • Vandetanib (ZD6474)

    Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM.

  • Cediranib (AZD2171)

    Cediranib (AZD2171) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM, similar activity against c-Kit and PDGFRβ, 36-, 110-fold and >1000-fold selective more for VEGFR than PDGFR-α, CSF-1R and Flt3, Phase 3.

  • Lenvatinib (E7080)

    Lenvatinib (E7080) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β. Phase 3.

Recently Viewed Items

Tags: buy Vatalanib (PTK787) 2HCl | Vatalanib (PTK787) 2HCl supplier | purchase Vatalanib (PTK787) 2HCl | Vatalanib (PTK787) 2HCl cost | Vatalanib (PTK787) 2HCl manufacturer | order Vatalanib (PTK787) 2HCl | Vatalanib (PTK787) 2HCl distributor
Contact Us