ARRY334543 is a selective and potent kinase ErbB-1 and ErbB-2 inhibitor with IC50 of 7 and 2 nM, respectively. The Ki of ARRY334543 is 1 nM. ARRY334543 behaves as a reversible ATP-competitive inhibitor with nanomolar potency both in vitro and in cell-based proliferation assays using A431 and BT-474 cells. ARRY334543 is an AKT pathway inhibitor in cells that contains active ErbB-2 receptors. ARRY334543 suppresses ErbB-2 and ErbB-1 phosphorylation in human cancer cells, such as BT-474 with an IC50 of 43 nM and A431 with an IC50 of 36 nM that overexpress ErbB-2 and ErbB-1, respectively. When dosed orally, ARRY334543 dose-dpendently inhibits growth of human tumor xenografts that overexpress ErbB-1 (A431) or ErbB-2 (MDA-MB-453). ARRY334543 demonstrates significant dose related tumor growth prevention when administered orally, BID, for 21 days. ARRY334543 has very good PK/ADME properties and has revealed excellent activity in numerous mouse tumor xenograft models including epidermoid (A431), breast (BT-474, MDA-MB-453), non-small cell lung (H1650, A549, 292), colorectal (Lovo, HT-29) and gastric (N87) carcinoma models. In the BT-474 model, ARRY334543 demonstrates significant dose-related tumor growth inhibition by 69% at 100 mg/kg/d and by 98% at 200 mg/kg/d. Excellent single agent activity for ARRY334543 in the SK-OV-3 ovarian carcinoma xenograft model as well as additive activity to trastuzumab in SK-OV-3, BT-474 and NCI-N87 models has been demonstrated. ARRY334543 exhibits excellent additive activity and tolerability with docetaxel. ARRY334543 is carried out in a phase II clinical trial in the treatment of advanced cancer and pancreatic cancer.
|Animal models||Athymic Ncr:Nu/Nu|
|Administration||Administered via p.o.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
|Related EGFR/HER2 Products|
Pertuzumab, a humanized monoclonal antibody and the first in the class of agents called the HER2 dimerization inhibitors, impairs the ability of HER2 to bind to other members of the HER family, MW: 148 KD.
Trastuzumab is a humanized, recombinant monoclonal antibody that binds to the extracellular domain of HER2, MW:145.53 KD.
Anlotinib is a EGFR inhibitor extracted from patent 2015185012 A1, compound 1，which can be used to treat non-small cell lung cancer.
Cetuximab, a novel molecular-targeted agent,is an inhibitor of EGFR monoclonal humanized antibody interacting with the extracellular binding site of EGFR to block ligand stimulation. MW : 145.781 KD.
EAI045 is an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.