WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H203110
CAS#: 212141-51-0 (HCl)
Description: Vatalanib, also known as PTK787, is an orally bioavailable anilinophthalazine with potential antineoplastic activity. Vatalanib binds to and inhibits the protein kinase domain of vascular endothelial growth factor receptors 1 and 2; both receptor tyrosine kinases are involved in angiogenesis. This agent also binds to and inhibits related receptor tyrosine kinases, including platelet-derived growth factor (PDGF) receptor, c-Kit, and c-Fms.
Hodoodo Cat#: H203110
Name: Vatalanib HCl
CAS#: 212141-51-0 (HCl)
Chemical Formula: C20H17Cl3N4
Exact Mass: 346.10
Molecular Weight: 419.730
Elemental Analysis: C, 57.23; H, 4.08; Cl, 25.34; N, 13.35
Related CAS #: 212141-51-0 (HCl) 212141-54-3 (free base) 212142-18-2 (succinate)
Synonym: PTK787; PTK 787; PTK-787; ZK 222584; ZK222584; ZK-222584; CGP 79787; CGP-797870; ZK-232934; CGP79787D; PTK787/ZK 222584; CGP-7978.
IUPAC/Chemical Name: N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine dihydrochloride.
InChi Key: AZUQEHCMDUSRLH-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H15ClN4.2ClH/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);2*1H
SMILES Code: ClC1=CC=C(NC2=NN=C(CC3=CC=NC=C3)C4=C2C=CC=C4)C=C1.[H]Cl.[H]Cl
Appearance: White to off-white crystalline solid
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: soluble in DMSO, not soluble in water.
Shelf Life: >10 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Related CAS# 212141-51-0 (Vatalanib 2HCl); 212141-54-3 (Vatalanib); 212142-18-2 (Vatalanib succinate).
| Biological target: | Vatalanib dihydrochloride (PTK787 dihydrochloride) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM. |
| In vitro activity: | As shown in Figure 2a, PDGF induced a marked increase in HSC proliferation, which was significantly inhibited by PTK/ZK (Vatalanib) in a dose-dependent manner. Incubation of HSCs with PDGF also dramatically increased HSC migration in BIOCOAT MATRIGEL chamber systems, whereas PTK/ZK significantly blocked the migration of HSC induced by PDGF (Figure 2b, P |
| In vivo activity: | Histological quantification of the fluorescence intensity of tau phosphorylation (Fig. 1f) revealed a significant decrease in AT8 immunoreactivity in the hippocampus (CA1 and DG) of vatalanib-treated 5xFAD mice compared with vehicle-treated 5xFAD mice (Fig. 1c, f). The fluorescence intensity of AT100 was also significantly decreased in the cortex and hippocampus DG of vatalanib-treated 5xFAD mice (Fig. 1d, f). However, the fluorescence intensity of Tau5 was not altered by the administration of vatalanib (Fig. 1e, f). Thus, vatalanib administration in 5xFAD mice significantly reduced phospho-tauSer202, Thr205 and phospho-tauThr212, Ser214 without altering total tau levels. Reference: Mol Brain. 2020; 13: 131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519542/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 53.3 | 127.06 | |
| DMSO:PBS (pH 7.2) (1:10) | 0.1 | 0.21 | |
| Ethanol | 6.0 | 14.29 | |
| Ethanol:PBS | 0.3 | 0.71 | |
| Water | 10.0 | 23.82 |
The following data is based on the product molecular weight 419.73 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Gaumann AK, Drexler HC, Lang SA, Stoeltzing O, Diermeier-Daucher S, Buchdunger E, Wood J, Bold G, Breier G. The inhibition of tyrosine kinase receptor signalling in leiomyosarcoma cells using the small molecule kinase inhibitor PTK787/ZK222584 (Vatalanib®). Int J Oncol. 2014 Dec;45(6):2267-77. doi: 10.3892/ijo.2014.2683. Epub 2014 Sep 29. PMID: 25340839; PMCID: PMC4215578. 2. Liu Y, Wen XM, Lui EL, Friedman SL, Cui W, Ho NP, Li L, Ye T, Fan ST, Zhang H. Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258. Lab Invest. 2009 Oct;89(10):1152-60. doi: 10.1038/labinvest.2009.77. Epub 2009 Aug 10. PMID: 19668241; PMCID: PMC2891536. 3. Jeon SG, Lee HJ, Park H, Han KM, Hoe HS. The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice. Mol Brain. 2020 Sep 25;13(1):131. doi: 10.1186/s13041-020-00673-7. PMID: 32977842; PMCID: PMC7519542. 4. Kong LJ, Li H, Du YJ, Pei FH, Hu Y, Zhao LL, Chen J. Vatalanib, a tyrosine kinase inhibitor, decreases hepatic fibrosis and sinusoidal capillarization in CCl4-induced fibrotic mice. Mol Med Rep. 2017 May;15(5):2604-2610. doi: 10.3892/mmr.2017.6325. Epub 2017 Mar 15. PMID: 28447731; PMCID: PMC5428398. |
| In vitro protocol: | 1. Gaumann AK, Drexler HC, Lang SA, Stoeltzing O, Diermeier-Daucher S, Buchdunger E, Wood J, Bold G, Breier G. The inhibition of tyrosine kinase receptor signalling in leiomyosarcoma cells using the small molecule kinase inhibitor PTK787/ZK222584 (Vatalanib®). Int J Oncol. 2014 Dec;45(6):2267-77. doi: 10.3892/ijo.2014.2683. Epub 2014 Sep 29. PMID: 25340839; PMCID: PMC4215578. 2. Liu Y, Wen XM, Lui EL, Friedman SL, Cui W, Ho NP, Li L, Ye T, Fan ST, Zhang H. Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258. Lab Invest. 2009 Oct;89(10):1152-60. doi: 10.1038/labinvest.2009.77. Epub 2009 Aug 10. PMID: 19668241; PMCID: PMC2891536. |
| In vivo protocol: | 1. Jeon SG, Lee HJ, Park H, Han KM, Hoe HS. The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice. Mol Brain. 2020 Sep 25;13(1):131. doi: 10.1186/s13041-020-00673-7. PMID: 32977842; PMCID: PMC7519542. 2. Kong LJ, Li H, Du YJ, Pei FH, Hu Y, Zhao LL, Chen J. Vatalanib, a tyrosine kinase inhibitor, decreases hepatic fibrosis and sinusoidal capillarization in CCl4-induced fibrotic mice. Mol Med Rep. 2017 May;15(5):2604-2610. doi: 10.3892/mmr.2017.6325. Epub 2017 Mar 15. PMID: 28447731; PMCID: PMC5428398. |
1: Giatromanolaki A, Koukourakis MI, Sivridis E, Gatter KC, Trarbach T, Folprecht G, Shi MM, Lebwohl D, Jalava T, Laurent D, Meinhardt G, Harris AL; Tumour and Angiogenesis Research Group. Vascular density analysis in colorectal cancer patients treated with vatalanib (PTK787/ZK222584) in the randomised CONFIRM trials. Br J Cancer. 2012 Sep 25;107(7):1044-50. doi: 10.1038/bjc.2012.369. Epub 2012 Aug 21. PubMed PMID: 22910317; PubMed Central PMCID: PMC3461163.
2: Wilson PM, Yang D, Azuma M, Shi MM, Danenberg KD, Lebwohl D, Sherrod A, Ladner RD, Zhang W, Danenberg PV, Trarbach T, Folprecht G, Meinhardt G, Lenz HJ. Intratumoral expression profiling of genes involved in angiogenesis in colorectal cancer patients treated with chemotherapy plus the VEGFR inhibitor PTK787/ZK 222584 (vatalanib). Pharmacogenomics J. 2012 Jun 5. doi: 10.1038/tpj.2012.23. [Epub ahead of print] PubMed PMID: 22664478.
3: Liu S, Xu C, Li G, Liu H, Xie J, Tu G, Peng H, Qiu S, Liang S. Vatalanib decrease the positive interaction of VEGF receptor-2 and P2X(2/3) receptor in chronic constriction injury rats. Neurochem Int. 2012 May;60(6):565-72. doi: 10.1016/j.neuint.2012.02.006. Epub 2012 Feb 15. PubMed PMID: 22361062.
4: Jones SF, Spigel DR, Yardley DA, Thompson DF, Burris HA 3rd. A phase I trial of vatalanib (PTK/ZK) in combination with bevacizumab in patients with refractory and/or advanced malignancies. Clin Adv Hematol Oncol. 2011 Nov;9(11):845-52. PubMed PMID: 22252616.
5: Jahan T, Gu L, Kratzke R, Dudek A, Otterson GA, Wang X, Green M, Vokes EE, Kindler HL. Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107). Lung Cancer. 2012 Jun;76(3):393-6. doi: 10.1016/j.lungcan.2011.11.014. Epub 2011 Dec 22. PubMed PMID: 22197613.
6: Koukourakis MI, Giatromanolaki A, Sivridis E, Gatter KC, Trarbach T, Folprecht G, Shi MM, Lebwohl D, Jalava T, Laurent D, Meinhardt G, Harris AL. Prognostic and predictive role of lactate dehydrogenase 5 expression in colorectal cancer patients treated with PTK787/ZK 222584 (vatalanib) antiangiogenic therapy. Clin Cancer Res. 2011 Jul 15;17(14):4892-900. doi: 10.1158/1078-0432.CCR-10-2918. Epub 2011 Jun 1. PubMed PMID: 21632858; PubMed Central PMCID: PMC3145151.
7: Gauler TC, Besse B, Mauguen A, Meric JB, Gounant V, Fischer B, Overbeck TR, Krissel H, Laurent D, Tiainen M, Commo F, Soria JC, Eberhardt WE. Phase II trial of PTK787/ZK 222584 (vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or progressing patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). Ann Oncol. 2012 Mar;23(3):678-87. doi: 10.1093/annonc/mdr255. Epub 2011 May 26. PubMed PMID: 21617019.
8: Joensuu H, De Braud F, Grignagni G, De Pas T, Spitalieri G, Coco P, Spreafico C, Boselli S, Toffalorio F, Bono P, Jalava T, Kappeler C, Aglietta M, Laurent D, Casali PG. Vatalanib for metastatic gastrointestinal stromal tumour (GIST) resistant to imatinib: final results of a phase II study. Br J Cancer. 2011 May 24;104(11):1686-90. doi: 10.1038/bjc.2011.151. Epub 2011 May 3. PubMed PMID: 21540861; PubMed Central PMCID: PMC3111164.
9: Spigel D, Jones S, Hainsworth J, Infante J, Greco FA, Thompson D, Doss H, Burris H. A phase I trial to determine the safety of imatinib in combination with vatalanib in patients with advanced malignancies. Cancer Invest. 2011 May;29(4):308-12. doi: 10.3109/07357907.2011.568567. PubMed PMID: 21469980.
10: Sobrero AF, Bruzzi P. Vatalanib in advanced colorectal cancer: two studies with identical results. J Clin Oncol. 2011 May 20;29(15):1938-40. doi: 10.1200/JCO.2010.33.2429. Epub 2011 Apr 4. PubMed PMID: 21464409.
11: Kłosowska-Wardęga A, Hasumi Y, Ahgren A, Heldin CH, Hellberg C. Combination therapy using imatinib and vatalanib improves the therapeutic efficiency of paclitaxel towards a mouse melanoma tumor. Melanoma Res. 2010 Oct 21. [Epub ahead of print] PubMed PMID: 20975605.
12: Gerstner ER, Eichler AF, Plotkin SR, Drappatz J, Doyle CL, Xu L, Duda DG, Wen PY, Jain RK, Batchelor TT. Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide. J Neurooncol. 2011 Jun;103(2):325-32. doi: 10.1007/s11060-010-0390-7. Epub 2010 Sep 7. PubMed PMID: 20821342.
13: Zhang YH, Yue ZJ, Zhang H, Tang GS, Wang Y, Liu JM. Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and angiogenesis in an orthotopic glioma model. Eur J Pharm Biopharm. 2010 Nov;76(3):371-5. doi: 10.1016/j.ejpb.2010.08.011. Epub 2010 Sep 9. PubMed PMID: 20816959.
14: Cook N, Basu B, Biswas S, Kareclas P, Mann C, Palmer C, Thomas A, Nicholson S, Morgan B, Lomas D, Sirohi B, Mander AP, Middleton M, Corrie PG. A phase 2 study of vatalanib in metastatic melanoma patients. Eur J Cancer. 2010 Oct;46(15):2671-3. doi: 10.1016/j.ejca.2010.07.014. Epub 2010 Aug 25. PubMed PMID: 20800475.
15: Paesler J, Gehrke I, Gandhirajan RK, Filipovich A, Hertweck M, Erdfelder F, Uhrmacher S, Poll-Wolbeck SJ, Hallek M, Kreuzer KA. 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 Jul 1;16(13):3390-8. doi: 10.1158/1078-0432.CCR-10-0232. Epub 2010 Jun 22. PubMed PMID: 20570929.
16: Jaeger-Lansky A, Cejka D, Ying L, Preusser M, Hoeflmayer D, Fuereder T, Koehrer S, Wacheck V. Effects of vatalanib on tumor growth can be potentiated by mTOR blockade in vivo. Cancer Biol Ther. 2010 Jun;9(11):919-27. Epub 2010 Jun 18. PubMed PMID: 20404549.
17: Chiorean EG, Malireddy S, Younger AE, Jones DR, Waddell MJ, Sloop MI, Yu M, Hall SD, Schneider B, Sweeney CJ. A phase I dose escalation and pharmacokinetic study of vatalanib (PTK787/ZK 222584) in combination with paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2010 Aug;66(3):441-8. doi: 10.1007/s00280-009-1179-2. Epub 2009 Nov 29. PubMed PMID: 20091169.
18: Lankheet AG, Hillebrand MJ, Langenberg MH, Rosing H, Huitema AD, Voest EE, Schellens JH, Beijnen JH. A validated assay for the quantitative analysis of vatalanib in human EDTA plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Nov 1;877(29):3625-30. doi: 10.1016/j.jchromb.2009.09.001. Epub 2009 Sep 6. PubMed PMID: 19762293.
19: Reardon DA, Egorin MJ, Desjardins A, Vredenburgh JJ, Beumer JH, Lagattuta TF, Gururangan S, Herndon JE 2nd, Salvado AJ, Friedman HS. Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma. Cancer. 2009 May 15;115(10):2188-98. doi: 10.1002/cncr.24213. PubMed PMID: 19248046; PubMed Central PMCID: PMC2691174.
20: Los M, Roodhart JM, Voest EE. Target practice: lessons from phase III trials with bevacizumab and vatalanib in the treatment of advanced colorectal cancer. Oncologist. 2007 Apr;12(4):443-50. Review. PubMed PMID: 17470687.
