Vandetanib

SKU: V0043

Category: API's & Intermediates

Synonyms: N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4-quinazolinamine , ZD6474 , Zactima , CH 331; 443913-73-3
CAS-Number: C₂₂H₂₄BrFN₄O₂
Molecular Formula: 475.35
Molecular Weight

Product Data
Handling
Safety Information
Details

Specifications

Purity: ≥98% (NMR)
Identity: 1H-NMR
Appearance: White to beige powder

Properties

Melting Point: 230 - 240° C
Solvents: Soluble in DMSO or DMF (5mg/ml).

Handling Advice: Protect from light and moisture.
Use / Stability: Stable for at least 2 years after receipt when stored at +4°C.
Long Term Storage: +4°C
Short Term Storage: +4°C
Shipping: AMBIENT

Transportation: Not dangerous goods
Signal word: Warning
GHS Symbol: GHS07
Precautionary statements: P261, P264, P271, P280, P302+P352, P304+P340+P312, P305+P351+P338, P332+P313, P337+P313, P362, P403+P233, P405, P501
Hazard statements: H315, H319, H335

Description: Vandetanib is an orally available, ATP mimetic small molecule tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor-2 (VEGFR-2), VEGFR-3 and epidermal growth factor receptor (EGFR), REarranged during Transfection (RET) and slightly VEGFR-1. Inhibition of these tyrosine kinases blocks multiple intracellular signaling pathways involved in tumor growth, proliferation, progression and angiogenesis. It inhibits RET, VEGFR2, VEGFR3, VEGFR1, EGFR, PDGFRβ, Tie-2, and FGFR1 in cell-free assays (IC50s = 34, 40, 110, 1,600, 500, 1,100, 2,500, and 3,600 nM, respectively). It also binds to 142 additional kinases in a panel of 442 kinases (Kds = 4.6-7,900 nM). Vandetanib (1 and 2.5 µM) induces apoptosis, autophagy, ROS and cell cycle arrest at the G0/G1 phase and has anti-proliferative properties in several cancer cell lines and in in vivo cancer models. Formulations containing vandetanib have been used in the treatment of medullary thyroid cancer.
InChi: 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)
References: (1) L.F. Hennequin, et al., J. Med. Chem. 45, 1300 (2002) , (2) F. Carlomagno, et al., Cancer Res. 62, 7284 (2002) , (3) S.R. Wedge, et al., Cancer Res. 62, 4645 (2002) , (4) F. Ciardiello, et al., Clin. Cancer Res. 9, 1546 (2003) , (5) J.N. Rich, et al., Clin. Cancer Res. 11, 8145 (2005) , (6) S. Sathornsumetee & J.N. Rich, Drugs Today 42, 657 (2006) (Review) , (7) R.S. Herbst, et al., Expert Opin. Investig. Drugs 16, 239 (2007) (Review) , (8) A. Morabito, et al., Oncologist 14, 378 (2009) (Review) , (9) M.I. Davis, et al., Nat. Biotechnol. 29, 1046 (2011) , (10) K. Inoue, et al., Clin. Cancer Res. 18, 3924 (2012) , (11) G.M. Keating, et al., BioDrugs 26, 431 (2012) (Review) , (12) S. Jasim, et al., Biologics 8, 281 (2014) , (13) M.W. Sim & M.S. Cohen, Expert Opin. Drug Discov. 9, 105 (2014) (Review)
InChi Key: UHTHHESEBZOYNR-UHFFFAOYSA-N
Smiles: BrC(C=C1F)=CC=C1NC2=NC=NC3=CC(OCC4CCN(C)CC4)=C(OC)C=C32

Vandetanib is an orally available, ATP mimetic small molecule tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor-2 (VEGFR-2), VEGFR-3 and epidermal growth factor receptor (EGFR), REarranged during Transfection (RET) and slightly VEGFR-1. Inhibition of these tyrosine kinases blocks multiple intracellular signaling pathways involved in tumor growth, proliferation, progression and angiogenesis. It inhibits RET, VEGFR2, VEGFR3, VEGFR1, EGFR, PDGFRβ, Tie-2, and FGFR1 in cell-free assays (IC50s = 34, 40, 110, 1,600, 500, 1,100, 2,500, and 3,600 nM, respectively). It also binds to 142 additional kinases in a panel of 442 kinases (Kds = 4.6-7,900 nM). Vandetanib (1 and 2.5 µM) induces apoptosis, autophagy, ROS and cell cycle arrest at the G0/G1 phase and has anti-proliferative properties in several cancer cell lines and in in vivo cancer models. Formulations containing vandetanib have been used in the treatment of medullary thyroid cancer.

SKU: V0043 Category: API's & Intermediates

Additional information

Additional information

Synonyms	N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4-quinazolinamine, ZD6474, Zactima, CH 331
Purity	≥98% (NMR)
Appearance	White to beige powder
CAS-Number	443913-73-3
Molecular Formula	C22H24BrFN4O2
Molecular Weight	475.35
Identity	1H-NMR
Solvents	Soluble in DMSO or DMF (5mg/ml).
Melting Point	230 – 240° C
Smiles	BrC(C=C1F)=CC=C1NC2=NC=NC3=CC(OCC4CCN(C)CC4)=C(OC)C=C32
InChi Key	UHTHHESEBZOYNR-UHFFFAOYSA-N
Shipping	AMBIENT
Short Term Storage	+4°C
Long Term Storage	+4°C
Handling Advice	Protect from light and moisture.
Use / Stability	Stable for at least 2 years after receipt when stored at +4°C.
Hazard statements	H315, H319, H335
Precautionary statements	P261, P264, P271, P280, P302+P352, P304+P340+P312, P305+P351+P338, P332+P313, P337+P313, P362, P403+P233, P405, P501
GHS Symbol	GHS07
Signal word	Warning
Transportation	Not dangerous goods
References	(1) L.F. Hennequin, et al., J. Med. Chem. 45, 1300 (2002), (2) F. Carlomagno, et al., Cancer Res. 62, 7284 (2002), (3) S.R. Wedge, et al., Cancer Res. 62, 4645 (2002), (4) F. Ciardiello, et al., Clin. Cancer Res. 9, 1546 (2003), (5) J.N. Rich, et al., Clin. Cancer Res. 11, 8145 (2005), (6) S. Sathornsumetee & J.N. Rich, Drugs Today 42, 657 (2006) (Review), (7) R.S. Herbst, et al., Expert Opin. Investig. Drugs 16, 239 (2007) (Review), (8) A. Morabito, et al., Oncologist 14, 378 (2009) (Review), (9) M.I. Davis, et al., Nat. Biotechnol. 29, 1046 (2011), (10) K. Inoue, et al., Clin. Cancer Res. 18, 3924 (2012), (11) G.M. Keating, et al., BioDrugs 26, 431 (2012) (Review), (12) S. Jasim, et al., Biologics 8, 281 (2014), (13) M.W. Sim & M.S. Cohen, Expert Opin. Drug Discov. 9, 105 (2014) (Review)
InChi	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)
Quantity	5 mg, 25 mg, Bulk