Orantinib (SU 6668; NSC-702827; TSU68)

Alias: Orantinib; NSC 702827; NSC-702827; NSC702827; TSU68; TSU-68; SU-6668; SU 6668; SU6668; NSC702827; TSU 68
Cat No.:V0519 Purity: ≥98%
Orantinib (formerly SU6668; TSU-68; NSC-702827; TSU 68; SU-6668) is a potent, orally bioavailable and multi-targeted receptor tyrosine kinase/RTK inhibitor with potential antineoplastic activity.
Orantinib (SU 6668; NSC-702827; TSU68) Chemical Structure CAS No.: 252916-29-3
Product category: VEGFR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
Other Sizes

Other Forms of Orantinib (SU 6668; NSC-702827; TSU68):

  • (Z)-Orantinib ((Z)-SU6668)
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Orantinib (formerly SU6668; TSU-68; NSC-702827; TSU 68; SU-6668) is a potent, orally bioavailable and multi-targeted receptor tyrosine kinase/RTK inhibitor with potential antineoplastic activity. In a cell-free assay, orantinib primarily inhibits the autophosphorylation of PDGFR with a Ki of 8 nM. It also potently inhibits the trans-phosphorylation of Flk-1 and FGFR1, with little to no activity against other kinases like EGFR, IGF-1R, Met, Src, Lck, Zap70, Abl, and CDK2. Additionally, orantinib has the potential to treat hepatocellular carcinoma and is currently undergoing clinical trials.

Biological Activity I Assay Protocols (From Reference)
Targets
PDGFRβ (Ki = 8 nM); FGFR1 (Ki = 1.2 μM); Flt-1 (Ki = 2.1 μM)
ln Vitro
Orantinib (SU6668; 0.03-10 μM) inhibits the tyrosine phosphorylation of KDR in VEGF-stimulated HUVECs and prevents PDGF-stimulated PDGFRβ tyrosine phosphorylation in NIH-3T3 cells that overexpress PDGFRβ. The phosphorylation of the FGFR1 substrate 2 is inhibited by orantinib (≥10 μM) when it is exposed to acidic FGF. Nonetheless, in NIH-3T3 cells overexpressing EGFR, orantinib (up to 100 μM) has no effect on EGF-stimulated EGFR tyrosine phosphorylation. Moreover, orantinib blocks HUVECs' ability to proliferate when stimulated by VEGF and FGF, with mean IC50 values of 0.34 μM and 9.6 μM, respectively[1]. Orantinib (SU6668) inhibits both ERK1/2 phosphorylation and the tyrosine autophosphorylation of the stem cell factor (SCF) receptor, c-kit, in human myeloid leukemia MO7E cells, with an IC50 of 0.1-1 μM. Furthermore, orantinib induces apoptosis and, at an IC50 of 0.29 μM, suppresses the proliferation of MO7E cells induced by SCF[2].
ln Vivo
Orantinib (SU6668; 75-200 mg/kg) inhibits the growth of various tumor types, including A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 cells, in xenograft models in athymic mice. C6 glioma xenograft tumor angiogenesis is likewise inhibited by orantinib (75 mg/kg)[1]. Orantinib (200 mg/kg) reduces average vessel permeability and average fractional plasma volume in the tumor rim and core of an HT29 human colon carcinoma tumor model. Around the edges of carcinomas, orantinib promotes aberrant stromal development[3]. In addition, a rabbit VX2 liver tumor model shows that Orantinib (TSU-68; 200 mg/kg) enhances the effects of chemotherapy infusion[4].
Enzyme Assay
Tyrosine kinase assays are used in 96-well microtiter plates that have been precoated (20 μg/well) in PBS and incubated overnight at 4 °C with the peptide substrate poly-Glu,Tyr (4:1). The purpose of these assays is to quantify the trans-phosphorylation activity of Flk-1 and FGFR1. One to five percent (w/v) BSA in PBS is used to block excess protein binding sites. The microtiter wells are then filled with purified GST-FGFR1 (kinase domain) or GST-Flk-1 (cytoplasmic domain) fusion proteins in a 2 × concentration kinase dilution buffer that contains 40 μM NaVO4, 50 mM NaCl, 100 mM HEPES, and 0.02% (w/v) BSA. For GST-Flk-1 and GST-FGFR1, the final enzyme concentration is 50 ng/mL. SU6668 is diluted 1:25 in H2O after being dissolved in DMSO at 100× the final required concentration. Each reaction well is then filled with 25 μL of diluted SU6668. Different concentrations of ATP are added to a solution of MnCl2 to start the kinase reaction. The final concentration of MnCl2 is 10 mM, and the final ATP concentrations span the Km for the enzyme. Before adding EDTA to stop the reaction, the plates are incubated for five to fifteen minutes at room temperature. TBST is then used to wash the plates three times. In TBST containing 0.5% (w/v) BSA, 0.025% (w/v) nonfat dry milk, and 100 μM NaVO4, rabbit polyclonal antiphosphotyrosine antisera are diluted 1: 10,000 and added to the wells. The incubation process lasts for one hour at 37 °C. Next, goat anti-rabbit antisera conjugated with HRP is added to the plates after three TBST washes. Three TBST washes are performed after the plates are incubated for an hour at 37 °C. After adding 2,2 to each well, the amount of phosphotyrosine is measured.
Cell Assay
In DMEM containing 10% (v/v) FBS, cells (HUVECs and NIH-3T3 cells overexpressing PDGFRβ or EGFR) are seeded (3 × 105 cells/35-mm well), grown to confluence, and then quiesced in DMEM containing 0.1% serum for two hours prior to drug treatment. After being seeded at a density of 2 × 106 cells/10-cm plate, HUVECs are grown to confluence in endothelial cell growth media and subsequently quiesce for 24 hours in endothelial cell basal media containing 0.5% FBS prior to drug treatment. Before being stimulated with ligand (100 ng/mL) for 10 minutes, all cell lines are incubated with SU6668 for 1 hour.
Animal Protocol
Mouse (Female, BALB/c, nu/nu) xenograft models of A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 tumor cells
75-200 mg/kg
Via i.p. injection or oral gavage once daily.
References

[1]. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res, 2000, 60(15), 4152-4160.

[2]. The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood, 2001, 97(5), 1413-1421.

[3]. In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. Clin Cancer Res, 2004, 10(2), 739-750.

[4]. Augmentation of chemotherapeutic infusion effect by TSU-68, an oral targeted antiangiogenic agent, in a rabbit VX2 liver tumor model. Cardiovasc Intervent Radiol. 2012 Feb;35(1):168-75.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C18H18N2O3
Molecular Weight
310.35
Exact Mass
310.13
Elemental Analysis
C, 69.66; H, 5.85; N, 9.03; O, 15.47
CAS #
252916-29-3
Appearance
Solid powder
SMILES
CC1=C(NC(=C1CCC(=O)O)C)/C=C\2/C3=CC=CC=C3NC2=O
InChi Key
NHFDRBXTEDBWCZ-ZROIWOOFSA-N
InChi Code
InChI=1S/C18H18N2O3/c1-10-12(7-8-17(21)22)11(2)19-16(10)9-14-13-5-3-4-6-15(13)20-18(14)23/h3-6,9,19H,7-8H2,1-2H3,(H,20,23)(H,21,22)/b14-9-
Chemical Name
3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid
Synonyms
Orantinib; NSC 702827; NSC-702827; NSC702827; TSU68; TSU-68; SU-6668; SU 6668; SU6668; NSC702827; TSU 68
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~62 mg/mL (~199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.2222 mL 16.1108 mL 32.2217 mL
5 mM 0.6444 mL 3.2222 mL 6.4443 mL
10 mM 0.3222 mL 1.6111 mL 3.2222 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00024206 Completed Other: pharmacological study
Drug: orantinib
Unspecified Adult Solid Tumor,
Protocol Specific
National Cancer Institute
(NCI)
July 2001 Phase 1
NCT00784290 Completed Drug: Orantinib
(TSU-68)
Hepatocellular Carcinoma Taiho Pharmaceutical Co., Ltd. September 2003 Phase 1
Phase 2
NCT01465464 Terminated Drug: Orantinib
(TSU-68)
Drug: Placebo
Hepatocellular Carcinoma Taiho Pharmaceutical Co., Ltd. December 2010 Phase 3
Biological Data
  • TSU-68 (SU6668, Orantinib)

    Efficacy of SU6668 on s.c. A431 xenograft growth in athymic mice.2000Aug 1;60(15):4152-60.

  • TSU-68 (SU6668, Orantinib)

    Effect of SU6668 on tumor xenograft angiogenesis.2000Aug 1;60(15):4152-60.

  • TSU-68 (SU6668, Orantinib)

    Efficacy of SU6668 against established A431 s.c. xenografts in athymic mice. A, SU6668 regresses established tumors in athymic mice.2000Aug 1;60(15):4152-60.

  • TSU-68 (SU6668, Orantinib)

    A, HUVECs;B, NIH-3T3 cells overexpressing PDGFRβ;C, NIH-3T3 cells;D, NIH-3T3 cells overexpressing EGFR.2000Aug 1;60(15):4152-60.

  • TSU-68 (SU6668, Orantinib)

    Inhibition of endothelial cell proliferation stimulated by either VEGF or FGF.2000Aug 1;60(15):4152-60.

  • TSU-68 (SU6668, Orantinib)

    Crystal structure of SU6668 in FGFR1 (left panel) and homology model of SU6668 in PDGFR (right panel).2000Aug 1;60(15):4152-60.

Contact Us