(E/Z)-CP-724714

(E/Z)-CP-724714 is a racemic compound of (E)-CP-724714 and (Z)-CP-724714 isomers. CP-724714 is a potent and selective orally active ErbB2 (HER2) inhibitor. (E/Z)-CP-724714 is a racemic compound of (E)-CP-724714 and (Z)-CP-724714 isomers. CP-724714 is a potent and selective orally active ErbB2 (HER2) inhibitor.

Product information

CAS Number: 537705-08-1

Molecular Weight: 469.53

Formula: C27H27N5O3

Synonym:

CP-724,714

Chemical Name: 2-methoxy-N-{3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-6-yl]prop-2-en-1-yl}acetamide

Smiles: COCC(=O)NCC=CC1C=CC2=NC=NC(NC3C=C(C)C(=CC=3)OC3=CC=C(C)N=C3)=C2C=1

InChiKey: LLVZBTWPGQVVLW-SNAWJCMRSA-N

InChi: InChI=1S/C27H27N5O3/c1-18-13-21(8-11-25(18)35-22-9-6-19(2)29-15-22)32-27-23-14-20(7-10-24(23)30-17-31-27)5-4-12-28-26(33)16-34-3/h4-11,13-15,17H,12,16H2,1-3H3,(H,28,33)(H,30,31,32)/b5-4+

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 94 mg/mL(200.2 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

CP-724, 714 is marked selectively against EGFR with IC50 of 6.4 μM. CP-724, 714 is >1, 000-fold less potent for IR, IGF-1R, PDGFRβ, VGFR2, abl. Src, c-Met c-jun NH2-terminal kinase (JNK)-2, JNK-3, ZAP-70, cyclin-dependent kinase (CDK)-2, and CDK-5. CP-724, 714 potently reduces the EGF-induced autophosphorylation of the chimera containing the erbB2 kinase domain with IC50 of 32 nM, but is markedly less potent against EGFR in transfected NIH3T3 cells. CP-724, 714 sensitively inhibits the proliferation of erbB2-amplified cells including BT-474 and SKBR3, with IC50 of 0.25 and 0.95 μM. CP-724, 714 induces the accumulation of cells in G1 phase and a marked reduction in S-phase in BT-474 cells at 1 μM. CP-724, 714 likely exerts its hepatotoxicity via both hepatocellular injury and hepatobiliary cholestatic mechanisms. CP-724, 714 displays inhibition of cholyl-lysyl fluorescein and taurocholate (TC) efflux into canaliculi in cryopreserved and fresh cultured human hepatocytes, respectively. CP-724, 714 inhibits TC transport in membrane vesicles expressing human bile salt export pump with IC50 of 16 μM and inhibits the major efflux transporter in bile canaliculi, MDR1, with IC50 of ~28 μM.

In Vivo:

CP-724, 714 (25 mg/kg) is rapidly absorbed after p.o. administration and causes reduction of tumor erbB2 receptor phosphorylation after dosing in FRE-erbB2 or BT-474 xenografts. CP-724, 714 induces apoptosis in FRE-erbB2 xenograft–bearing (s.c.) mice and shows 50% tumor growth inhibition at 50 mg/kg, without weight loss or mortality. CP-724, 714 also has great antitumor activity in MDA-MB-453, MDA-MB-231, LoVo (colon), and Colo-205 (colon) xenografts. Furthermore, CP-724, 714 (30 or 100 mg/kg) reduces the extracellular signal–regulated kinase and Akt phosphorylation in BT-474 xenografts.

References:

1. Feng B, et al. Toxicol Sci, 2009, 108(2), 492-500.
2. Jani JP, et al. Cancer Res, 2007, 67(20), 9887-9893.

Products are for research use only. Not for human use.