Derazantinib

SKU: orb1296116

Description

Derazantinib (ARQ-087) is an orally bioavailable, ATP-competitive inhibitor targeting fibroblast growth factor receptors (FGFRs) with low nanomolar potency. It is used in research to investigate FGFR-driven pathologies, demonstrating activity in both in vitro assays and in vivo tumor models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1234356-69-4
• MW: 468.57
• Purity: 99.95%
• Formula: C₂₉H₂₉FN₄O
• SMILES: COCCNCCc1cccc(Nc2ncc3C[C@@H](c4ccccc4F)c4ccccc4-c3n2)c1
• Target: FGFR
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.04 mM);DMSO:98 mg/mL (209.15 mM)

Bioactivity

• Target IC50:
  FGFR3:4.5 nM|FGFR1:4.5 nM|FGFR2:1.8 nM
• In Vivo:
  METHODS: Derazantinib (ARQ-087) (25, 50, 75 mg/kg) treated SNU-16 and NCI-H716 xenograft athymic mouse models; Derazantinib (50, 100, 150 mg/kg) treated Ba/F3-FGFR2 xenograft athymic mouse models Thymic mouse model; Derazantinib (75 mg/kg) treated Ba/F3-INSR xenograft athymic mouse model; both were administered orally and the in vivo anti-tumor effect of Derazantinib was evaluated. RESULTS Derazantinib showed potent tumor growth inhibition in the Ba/F3-FGFR2 model but failed to inhibit the growth of the Ba/F3-INSR model; in the SNU-16 xenograft study, 75 mg/kg and 50 mg /kg treatment achieved TGI of 83% and 69%, respectively; in the NCI-H716 human cecum model, 50 mg/kg and 75 mg/kg showed significant TGI of 68% and 96%, respectively.
• In Vitro:
  METHODS: COS-1 cells ectopically expressing FGFR1, FGFR2, FGFR3, or FGFR4 were treated with derazantinib (ARQ-087) (0.1, 0.3, 1.1, 3.3, 10 μM, 2 hours) and stimulated with 100 pM FGF1/2/7 for 15 minutes. Total and phosphorylated FGFRs were assessed by Western blot analysis. RESULTS Derazantinib inhibited phosphorylation of FGFR1, FGFR2, FGFR3, and FGFR4 with IC50 values ​​of <0.123 μM, 0.185 μM, 0.463 μM, and >10 μM, respectively, together with EC.
• Cell Research:
  Cells are seeded at 3000-5000 cells per well with 130 μL media in 96-well tissue culture-treated plates. The cells are incubated overnight and subsequently treated with 3-fold serial dilutions of Derazantinib starting at 100 μM. The cells are returned to a 37°C humidified incubator for 72 hours. Cell proliferation is measured using the MTS assay .
• Animal Research:
  Female NCr nu/nu mice (SNU-16) or CB17 SCID mice (NCI-H716) with well established (400 mg) subcutaneous tumors are given a single oral dose of Derazantinib or vehicle control. Plasma and tumor samples are collected 4 hours post single dose. Derazantinib is administered orally. The dosing volume for all groups is 10 mL/kg or 0.1 mL/10 g body weight .

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

ARQ 087, ARQ087, ARQ-087, Derazantinib, inhibit, Inhibitor, Fibroblast growth factor receptor, FGFR, FGFR1, FGFR2, FGFR3

Compound Identifiers

PubChem CID

46834118