BMS-754807

SKU: orb1305620

Description

BMS-754807 is an orally bioavailable small molecule that potently inhibits the tyrosine kinase activity of both IGF-1R and InsR. This dual inhibition has demonstrated antitumor activity in preclinical studies, supporting its investigation in cancer research models both in vitro and in vivo.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1001350-96-4
• MW: 461.49
• Purity: 99.94% (May vary between batches)
• Formula: C₂₃H₂₄FN₉O
• SMILES: C[C@]1(CCCN1c1nc(Nc2cc([nH]n2)C2CC2)c2cccn2n1)C(=O)Nc1ccc(F)nc1
• Target: Trk receptor,c-Met/HGFR,IGF-1R
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.15 mM);Ethanol:85 mg/mL (184.19 mM);DMSO:240 mg/mL (520.05 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Insulin receptor:1.7 nM|IGF-1R:1.8 nM|MET:5.6 nM|TrkA:7.4 nM|TrkB:4.1 nM
• In Vivo:
  BMS-754807 inhibits the phosphorylation of IGF-1R in IGF-1R-Sal cells, Rh41, and Geo with IC50 values of 13 nM, 6 nM, and 21 nM, respectively. It similarly inhibits the phosphorylation of Akt in these cells, with IC50 values of 22 nM, 13 nM, and 16 nM. Additionally, BMS-754807 induces apoptosis in Rh41 cells and suppresses the proliferation of IGF-1R-Sal and Rh41 cells, with IC50 values of 7 nM and 5 nM, respectively. In the pediatric preclinical testing program (PPTP), BMS-754807 exhibited activity across 23 cell lines with an average EC50 value of 0.62 μM, covering a range of cell types including mesenchymal (Ewing's, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, and gastric cancers), and hematopoietic stem cells (multiple myeloma and leukemia), with IC50 values spanning from 5 nM to 365 nM.
• In Vitro:
  MS-754807 (6.25 mg/kg) achieved complete tumor growth inhibition in a transgenic-derived IGF-Sal tumor model in mice, while simultaneously inhibiting associated pIGF-1R and pAKT. In nude mice with IGF-1R-Sal tumors, BMS-754807 (12.5 mg/kg, orally) inhibited tumor and serum IGF-1R phosphorylation. At a dose of 25 mg/kg, BMS-754807 significantly inhibited tumor growth in mouse models carrying KT-5 (Wilms), KT-14 (rhabdoid), Rh28 (rhabdomyosarcoma), and OS-1 xenografts. Furthermore, BMS-754807 effectively suppressed tumor growth across a selection of epithelial (IGF-1R-Sal, GEO, and Colo205), hematopoietic (JJN3), and mesenchymal (RD1 and Rh41) xenograft models, with tumor growth inhibition rates ranging from 53% to 115%.
• Cell Research:
  Cells are grown at their optimal density in RPMI +GlutaMax supplemented with 10% heat-inactivated fetal bovine serum (FBS), 10 mM Hepes, penicillin, and streptomycin. Cell proliferation is evaluated by incorporation of 3H-thymidine into DNA after exposure of cells to BMS-754807 for 72 hours. Results are expressed as an IC50, which is the drug concentration required to inhibit cell proliferation by 50% compared with untreated control cells.(Only for Reference)

Storage & Handling

• Storage: 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 754807, BMS754807, BMS-754807, cMet, c-Met, cMet/HGFR, Met, inhibit, HGFR, Inhibitor, Insulin Receptor, IGF-1R, IGF1R, Trk receptor, TrkA, TrkB, Trkreceptor

Compound Identifiers

PubChem CID

24785538