Vandetanib | CAS#443913-73-3 | Tyrosine Kinase Inhibitor

MedKoo Cat#: 558308 | Name: Vandetanib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Vandetanib is an orally bioavailable 4-anilinoquinazoline. Vandetanib selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGF2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis. Vandetanib was the first drug to be approved by FDA (April 2011) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery. Vandetanib was approved in 2011.

Chemical Structure

Vandetanib

CAS#443913-73-3 (free base)

Theoretical Analysis

MedKoo Cat#: 558308

Name: Vandetanib

CAS#: 443913-73-3 (free base)

Chemical Formula: C22H24BrFN4O2

Exact Mass: 474.1067

Molecular Weight: 475.35

Elemental Analysis: C, 55.59; H, 5.09; Br, 16.81; F, 4.00; N, 11.79; O, 6.73

Price and Availability

Size	Price	Availability
500mg	USD 150.00	Ready to ship
1g	USD 250.00	Ready to ship
2g	USD 450.00	Ready to ship
5g	USD 950.00	2 Weeks
10g	USD 1,650.00	2 Weeks

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Related CAS #

443913-73-3 (free base) 338992-00-0 (fumarate)

Synonym

AZD6474; AZD 6474; AZD-6474; ZD6474; ZD 6474; ZD-6474; CHEBI:38942; Vandetanib; Zactim; Caprelsa

IUPAC/Chemical Name

N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine

InChi Key

UHTHHESEBZOYNR-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)

SMILES Code

CN1CCC(COC2=CC3=NC=NC(NC4=CC=C(Br)C=C4F)=C3C=C2OC)CC1

Appearance

Light yellow to yellow solid powder

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 in water

Shelf Life

>2 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

Vandetanib is being developed by AstraZeneca. In April 2011, Vandetanib became the first drug to be approved by FDA for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery. Vandetanib was first initially marketed without a tradename, and is being marketed under the trade name Caprelsa since August 2011. (source: http://en.wikipedia.org/wiki/ Vandetanib ). Vandetanib is also a medication currently undergoing clinical trials as a potential targeted treatment for non-small-cell lung cancer. There have been some promising results from a phase III trial with docetaxel. There have also been ambivalent results when used with pemetrexed. Another trial with docetaxel was recruiting in July 2009. AstraZeneca withdrew EU regulatory submissions for Zactima in October 2009 after trials showed no benefit when the drug was administered alongside chemotherapy. (source: http://en.wikipedia.org/wiki/ Vandetanib ).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC10725

QC Data

View QC data: current batch, Lot#TZC10725

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Vandetanib (D6474) is an inhibitor of VEGFR2/KDR tyrosine kinase activity (IC50=40 nM).

In vitro activity:

As shown in Figure 1, vandetanib can significantly reduce cell proliferation compared with control and NC groups. About 12 hours after treatment, cell viability decreased about half by MTT assay. This study hypothesized that apoptosis might be the cause of this effect. Therefore, Annexin V/PI staining was performed for three groups at 24 hours after treatment. Flow cytometry assay showed that vandetanib group produced about four folds more Annexin V/PI double positive cells compared with other two groups. Cell cycle analysis was performed. As to G2/M phage, there was significant reduction compared with control group (P<0.05). As to G0/G1 phage, the percentage was improved (P>0.05). Thus, vandetanib inhibited the proliferation of breast cancer cells through regulating G2/M phage and subsequently contributed to growth inhibition. Reference: Onco Targets Ther. 2018; 11: 8543–8553. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278704/

In vivo activity:

To investigate the antitumor activity of vandetanib in tumors harboring the activating Egfr mutation, 7-week-old transgenic mice were administered vandetanib (6mg/kg) or vehicle daily for 7 days, after which they were killed. After administering vandetanib for 2 days, the area occupied by tumor cells decreased compared with the pre-administration value (Fig. 1B, C). Furthermore, tumor cell disappeared in the seeing length after the administration of vandetanib for 7 days (Fig. 1D). The expression of total EGFR and total VEGFR2 in the lungs of the transgenic mice, as assessed by immunohistochemistry, was slightly suppressed in the vandetanib-treated animals compared to the animals treated with vehicle alone, while the pEGFR and pVEGFR levels were markedly decreased in the transgenic mice treated with vandetanib relative to those treated with vehicle (Fig. 2). Reference: Acta Med Okayama. 2016 Aug;70(4):243-53. https://pubmed.ncbi.nlm.nih.gov/27549668/

	Solvent	mg/mL	mM
Solubility
	DMSO	22.5	47.33
	DMF	2.0	4.21
	DMF:PBS (pH 7.2) (1:1)	0.5	1.05

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 475.35 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. Li L, Yu J, Jiao S, Wang W, Zhang F, Sun S. Vandetanib (ZD6474) induces antiangiogenesis through mTOR-HIF-1 alpha-VEGF signaling axis in breast cancer cells. Onco Targets Ther. 2018 Nov 29;11:8543-8553. doi: 10.2147/OTT.S175578. PMID: 30555244; PMCID: PMC6278704. 2. Zhou Y, Zhang Y, Zou H, Cai N, Chen X, Xu L, Kong X, Liu P. The multi-targeted tyrosine kinase inhibitor vandetanib plays a bifunctional role in non-small cell lung cancer cells. Sci Rep. 2015 Feb 27;5:8629. doi: 10.1038/srep08629. PMID: 25720956; PMCID: PMC4342569. 3. Osawa M, Ohashi K, Kubo T, Ichihara E, Takata S, Takigawa N, Takata M, Tanimoto M, Kiura K. Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation. Acta Med Okayama. 2016 Aug;70(4):243-53. doi: 10.18926/AMO/54499. PMID: 27549668. 4. Hatem R, Labiod D, Château-Joubert S, de Plater L, El Botty R, Vacher S, Bonin F, Servely JL, Dieras V, Bièche I, Marangoni E. Vandetanib as a potential new treatment for estrogen receptor-negative breast cancers. Int J Cancer. 2016 May 15;138(10):2510-21. doi: 10.1002/ijc.29974. Epub 2016 Jan 6. PMID: 26686064.

In vitro protocol:

In vivo protocol:

1. Osawa M, Ohashi K, Kubo T, Ichihara E, Takata S, Takigawa N, Takata M, Tanimoto M, Kiura K. Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation. Acta Med Okayama. 2016 Aug;70(4):243-53. doi: 10.18926/AMO/54499. PMID: 27549668. 2. Hatem R, Labiod D, Château-Joubert S, de Plater L, El Botty R, Vacher S, Bonin F, Servely JL, Dieras V, Bièche I, Marangoni E. Vandetanib as a potential new treatment for estrogen receptor-negative breast cancers. Int J Cancer. 2016 May 15;138(10):2510-21. doi: 10.1002/ijc.29974. Epub 2016 Jan 6. PMID: 26686064.

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PMID: 39692930; PMCID: PMC11656002. 4: Rouseti GM, Fischer A, Rathfelder N, Grimes K, Waldt A, Cuttat R, Schuierer S, Wild S, Jivkov M, Dubost V, Schadt HS, Odermatt A, Vicart A, Moretti F. Disruption of serotonin homeostasis in intestinal organoids provides insights into drug-induced gastrointestinal toxicity. Toxicology. 2024 Dec 4;511:154028. doi: 10.1016/j.tox.2024.154028. Epub ahead of print. PMID: 39643203. 5: Pinto-Fraga J, García-Chico C, Lista S, Lacal PM, Carpenzano G, Salvati M, Santos-Lozano A, Graziani G, Ceci C. protein kinase inhibitors as Targeted therapy for glioblastoma: A meta-analysis of randomized controlled clinical trials. Pharmacol Res. 2024 Dec 3:107528. doi: 10.1016/j.phrs.2024.107528. Epub ahead of print. PMID: 39637954. 6: Lasolle H, Borson-Chazot F, Gauduchon T, Haissaguerre M, Illouz F, Lifante JC, Lussey-Lepoutre C, Prunier D, Sajous C, Varnier R, Hadoux J. La prise en charge des cancers médullaires de la thyroïde en 2024. Bull Cancer. 2024 Oct;111(10S1):10S53-10S63. French. doi: 10.1016/S0007-4551(24)00408-9. PMID: 39505437. 7: Zhou Y, Li N, Ma G, Su N, Liu J, Yue W, Yin R, Chen J. Mining and analysis of adverse event signals of vandetanib based on the FAERS database. Expert Opin Drug Saf. 2024 Oct 22:1-8. doi: 10.1080/14740338.2024.2418326. Epub ahead of print. PMID: 39434712. 8: Nervo A, Ferrari M, Vaccaro E, Migliore E, Gruosso G, Roux A, Piovesan A, Arvat E. Tailored management of advanced thyroid cancer patients treated with lenvatinib or vandetanib: the role of a multimodal approach. Endocrine. 2024 Oct 2. doi: 10.1007/s12020-024-04061-2. Epub ahead of print. PMID: 39356445. 9: Zhang Y, Zheng WH, Zhou SH, Gu JL, Yu Q, Zhu YZ, Yan YJ, Zhu Z, Shang JB. Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives. Cell Commun Signal. 2024 Sep 28;22(1):460. doi: 10.1186/s12964-024-01837-x. PMID: 39342195; PMCID: PMC11439284. 10: Zhang Y, Zhang X, Lin L, Xing M. Efficacy and safety of targeted therapy for radioiodine-refractory differentiated thyroid cancer: a meta-analysis. J Clin Endocrinol Metab. 2024 Sep 18:dgae617. doi: 10.1210/clinem/dgae617. Epub ahead of print. PMID: 39292866. 11: Zhou M, Lin Y, Chen H, Zhao M, Zeng Y, Hu X, Tang P, Fu Y, Wei L, Han L. Brain-tumor-seeking and serpin-inhibiting outer membrane vesicles restore plasmin-mediated attacks against brain metastases. J Control Release. 2024 Nov;375:116-126. doi: 10.1016/j.jconrel.2024.09.003. Epub 2024 Sep 6. PMID: 39236899. 12: Tan L, Ni Y, Huang Z, Yan J, Wu M, Zhang Z, Zhang F, Wang Z. Efficacy and safety of VEGFR inhibitors for recurrent ovarian cancer: a systematic review. Future Oncol. 2024;20(26):1943-1960. doi: 10.1080/14796694.2024.2373680. Epub 2024 Aug 12. PMID: 39129672; PMCID: PMC11498025. 13: Wirth LJ, Brose MS, Subbiah V, Worden F, Solomon B, Robinson B, Hadoux J, Tomasini P, Weiler D, Deschler-Baier B, Tan DSW, Maeda P, Lin Y, Singh R, Bayt T, Drilon A, Cassier PA. Durability of Response With Selpercatinib in Patients With RET-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001. J Clin Oncol. 2024 Sep 20;42(27):3187-3195. doi: 10.1200/JCO.23.02503. Epub 2024 Aug 2. PMID: 39094065; PMCID: PMC11404750. 14: Jing R, Wu N, Wu Y, Zhang Q, Liang Q, Huang P, Yi S. Efficacy and Safety of Multikinase Inhibitors for Patients With Refractory Thyroid Cancer: Systematic Review and Network Meta-Analysis. J Clin Endocrinol Metab. 2024 Sep 16;109(10):2658-2672. doi: 10.1210/clinem/dgae454. PMID: 38970485. 15: Darwish IA, Darwish HW, Alsalhi MS. A One-Step Green Microwell Spectrophotometric Assay for the Determination of Certain New Chemotherapeutic Drug Formulations. 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