BMS-690514

SKU: orb1707533

Description

BMS-690514 is an orally bioavailable small molecule that potently inhibits EGFR, VEGFR, and HER family kinases, with IC50 values of 5 nM (EGFR), 20 nM (HER2), and 60 nM (HER4). It has been utilized in preclinical cancer research to study angiogenesis and tumor growth inhibition in both cellular assays and animal models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 859853-30-8
• MW: 368.43
• Purity: 99.08% (May vary between batches)
• Formula: C₁₉H₂₄N₆O₂
• SMILES: COc1cccc(Nc2ncnn3ccc(CN4CC[C@@H](N)[C@H](O)C4)c23)c1
• Target: EGFR,VEGFR,HER
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.43 mM);DMSO:24 mg/mL (65.14 mM)

Bioactivity

• Target IC50:
  HER4:60 nM|HER2:20 nM|EGFR:5 nM
• In Vivo:
  BMS-690514 can traverse the blood-brain barrier, evidenced by a brain-to-plasma ratio of 1, and exhibits efficacy against a wide range of tumor xenografts. At doses both efficacious and tolerable in animal models, it effectively inhibits tumor cell proliferation and reduces tumor blood flow. Preclinical absorption, distribution, metabolism, and excretion (ADME) studies indicate BMS-690514 possesses favorable oral bioavailability in humans, undergoing metabolism predominantly through oxidation and glucuronidation. Specifically, its oral bioavailability is reported at 78% in mice, 100% in rats, 8% in monkeys, and 29% in dogs.
• In Vitro:
  BMS-690514 inhibits members of the VEGFR family with IC50 values in the range of 25 to 50 nM. BMS-690514 targets several critical signaling pathways: human epidermal growth factor receptor (HER)/ErbB, angiogenesis signaling through VEGFR2, lymphangiogenesis through VEGFR3, respectively. It also shows activity against VEGFR1, Flt-3, and Lck. Permeability of BMS-690514 in Caco-2 cells is in the intermediate range with a moderate potential to be a P-gp substrate. Non–small cell lung tumor cells with exon 19 deletion (HCC4006, HCC827, and PC9) are highly sensitive to BMS-690514, which inhibits their proliferation with IC50 values of 2 to 35 nM. Tumor cell lines with EGFR gene amplification (DiFi, NCI-H2073, A431) are also highly sensitive to inhibition by BMS-690514. Breast and gastric tumor cell lines that have HER2 gene amplification (N87, SNU-216, AU565, BT474, KPL4, and HCC202) are inhibited with IC50 values of 20 to 60 nM. Tumor cell lines that are dependent on HER2 signaling are also found to be highly sensitive to BMS-690514.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BMS 690514, BMS690514, BMS-690514, inhibit, Inhibitor, HER2, HER4, HER1, Epidermal growth factor receptor, ErbB-1, EGFR, Vascular endothelial growth factor receptor, VEGFR

Compound Identifiers

PubChem CID

11349170