Orantinib

SKU: orb1301001

Description

Orantinib (NSC 702827) is a potent, selective inhibitor of PDGFR (Ki = 8 nM), Flk-1, and FGFR1 tyrosine kinases, with minimal activity against IGF-1R, Met, Src-family kinases, Abl, CDK2, and EGFR. It has been utilized in preclinical cancer research, demonstrating anti-angiogenic and antitumor efficacy in various in vitro and in vivo models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 252916-29-3
• MW: 310.35
• Purity: 100.00% (May vary between batches)
• Formula: C₁₈H₁₈N₂O₃
• SMILES: Cc1[nH]c(\C=C2/C(=O)Nc3ccccc23)c(C)c1CCC(O)=O
• Target: PDGFR|||FGFR|||Apoptosis|||VEGFR
• Solubility: DMSO:40 mg/mL (128.89 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:10 mg/mL (32.22 mM);1eq. NaOH:31 mg/mL (99.89 mM)

Bioactivity

• Target IC50:
  FLT1:2.1 μM (Ki)|FGFR1:1.2 μM (Ki)|PDGFRβ:8 nM(Ki)
• In Vivo:
  TSU-68 is an ATP-competitive inhibitor that acts on Flk-1/KDR, FGFR1, and PDGFRβ kinase phosphorylation with respective Ki values of 2.1 μM, 1.2 μM, and 8 nM. In human megakaryoblastic leukemia MO7E cells, TSU-68 (IC50=0.1-1 μM) inhibits the tyrosine autophosphorylation of the c-kit receptor for hepatocyte growth factor and the phosphorylation of ERK1/2. It also suppresses cell proliferation and induces apoptosis in MO7E cells stimulated by SCF, with an IC50 of 0.29 μM. In NIH-3T3 cells overexpressing PDGFRβ, TSU-68 (0.03-0.1 μM) inhibits the PDGFRβ tyrosine phosphorylation stimulated by PDGF. Additionally, in human umbilical vein endothelial cells (HUVECs) stimulated by vascular endothelial growth factor, TSU-68 (0.03-10 μM) prevents KDR tyrosine phosphorylation. However, in NIH-3T3 cells overexpressing EGFR, TSU-68 (100 μM) does not inhibit the tyrosine phosphorylation of EGFR stimulated by EGF. Furthermore, TSU-68 inhibits the proliferation of HUVECs driven by vascular endothelial growth factor and FGF, with average IC50 values of 0.34 and 9.6 μM, respectively.
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• In Vitro:
  In the HT29 human colorectal cancer tumor model, TSU-68 (200 mg/kg) reduced the average vascular permeability at the tumor margin and the average plasma volume fraction at the tumor center. In athymic mice bearing various xenografts, including A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 cells, TSU-68 (75-200 mg/kg) inhibited cell growth. In the rabbit VX2 liver tumor model, TSU-68 (200 mg/kg) enhanced the efficacy of injected chemotherapy. Additionally, in C6 glioma xenografts, TSU-68 (75 mg/kg) also blocked tumor angiogenesis.
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• Cell Research:
  Cells are seeded (3 × 105 cells/35-mm well) in DMEM containing 10% (v/v) FBS and grow to confluence and then quiesced in DMEM containing 0.1% serum for 2 hours before drug treatment. HUVECs (seeded at 2 × 106 cells/10-cm plate) are grown to confluence in endothelial cell growth media and then quiesced in endothelial cell basal media containing 0.5% FBS for 24 hours before drug treatment. All cell lines are incubated with SU6668 for 1 hour before ligand stimulation (100 ng/mL) for 10 min. Western blotting is perfor (Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, NSC 702827, Orantinib, Platelet-derived growth factor receptor, NSC702827, NSC-702827, Fibroblast growth factor receptor, FGFR, FGFR1, Flk1, Inhibitor, Apoptosis, PDGFR, PDGFRβ, SU6668, SU-6668, SU 6668, Vascular endothelial growth factor receptor, VEGFR, TSU 68, TSU68, TSU-68

Compound Identifiers

PubChem CID

5329099