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Purity: ≥98%
Motesanib, the diphosphate salt of Motesanib (formerly AMG706) is an ATP-competitive and orally bioavailable inhibitor of vascular endothelial growth factor (VEGFR1/2/3) with potential antitumor activity. Its IC50s are 2 nM, 3 nM, and 6 nM for VEGFR1/2/3 inhibition, respectively.
| Targets |
VEGFR1 (IC50 = 2 nM); VEGFR2 (IC50 = 3 nM); VEGFR2/Flk1 (IC50 = 6 nM); VEGFR3 (IC50 = 6 nM); Kit (IC50 = 8 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Homogeneous time-resolved fluorescence (HTRF) assays are used to determine suitable enzyme, ATP, and substrate (gastrin peptide) concentrations for each enzyme. Using a two-thirds Km ATP concentration for each enzyme, motesanib is tested in a 10-point dose-response curve. An enzyme is combined with kinase reaction buffer (20 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 5 mM MnCl2, 100 mM NaCl, 1.5 mM EGTA) in the majority of assays. Prior to each experiment, a final concentration of 20 μg/mL BSA, 0.2 mM NaVO4, and 1 mM DTT is added. The HTRF reaction is preceded in all assays by the addition of 0.1125 nM Eu-PT66 and 5.75 mg/mL streptavidin-allophycocyanin. Using a Discovery instrument, plates are read after 30 minutes of room temperature incubation. Levenberg-Marquardt algorithm is used to calculate IC50 values, which are then entered into a four-parameter logistic equation.
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| Cell Assay |
After exposing the cells to either 50 ng/mL VEGF or 20 ng/mL bFGF for an extra 72 hours, the cells are preincubated for two hours at varying concentrations of motesanib. Plates are frozen for 24 hours at -70°C after cells are twice cleaned with DPBS. Plates are read using a Victor 1420 workstation, and proliferation is measured by adding CyQuant dye. The four-parameter logistic equation is derived from the IC50 data using the Levenberg-Marquardt algorithm.
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| Animal Protocol |
DMEM (low glucose) supplemented with 10% FBS, penicillin, streptomycin, and glutamine is used to cultivate A431 cells. Trypsinization is used to harvest the cells, which are then cleaned and concentrated to 5×107/mL in serum-free medium. 1x107 cells in 0.2 mL are given to the animals s.c. over the left flank as a challenge. After about ten days, mice are treated with either vehicle (Ora-Plus) or motesanib, according to initial tumor volume measurements. Body weights and tumor volumes are measured twice a week, as well as on the day of sacrifice. Using a Pro-Max electronic digital caliper, the tumor volume is measured and expressed in millimeter-three (mm3) by calculating the formula length (mm)×width (mm)×height (mm). The data is presented as mean±SE. Repeated actions ANOVA is used to assess the statistical significance of observed differences, with Scheffe post hoc testing for multiple comparisons used afterward[1].
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| References |
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| Additional Infomation |
Motesanib Diphosphate is the orally bioavailable diphosphate salt of a multiple-receptor tyrosine kinase inhibitor with potential antineoplastic activity. Motesanib selectively targets and inhibits vascular endothelial growth factor (VEGFR), platelet-derived growth factor (PDGFR), kit, and Ret receptors, thereby inhibiting angiogenesis and cellular proliferation.
See also: Motesanib (annotation moved to). |
| Molecular Formula |
C22H29N5O9P2
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|---|---|
| Molecular Weight |
569.44
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| Exact Mass |
569.144
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| Elemental Analysis |
C, 46.40; H, 5.13; N, 12.30; O, 25.29; P, 10.88
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| CAS # |
857876-30-3
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| Related CAS # |
Motesanib;453562-69-1
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| PubChem CID |
16097729
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| Appearance |
White to off-white solid powder
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| Boiling Point |
858.7ºC at 760 mmHg
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| Flash Point |
473.1ºC
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| LogP |
2.781
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| Hydrogen Bond Donor Count |
9
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
38
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| Complexity |
583
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| Defined Atom Stereocenter Count |
0
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| SMILES |
P(=O)(O[H])(O[H])O[H].P(=O)(O[H])(O[H])O[H].O=C(C1C([H])=C([H])C([H])=NC=1N([H])C([H])([H])C1C([H])=C([H])N=C([H])C=1[H])N([H])C1C([H])=C([H])C2=C(C=1[H])N([H])C([H])([H])C2(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
ONDPWWDPQDCQNJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N5O.2H3O4P/c1-22(2)14-26-19-12-16(5-6-18(19)22)27-21(28)17-4-3-9-24-20(17)25-13-15-7-10-23-11-8-15;2*1-5(2,3)4/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28);2*(H3,1,2,3,4)
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| Chemical Name |
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide;phosphoric acid
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| Synonyms |
AMG-706; Motesanib Diphosphate; AMG 706; AMG706; motesanib phosphate;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 25 mg/mL (43.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 250.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Saline: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7561 mL | 8.7806 mL | 17.5611 mL | |
| 5 mM | 0.3512 mL | 1.7561 mL | 3.5122 mL | |
| 10 mM | 0.1756 mL | 0.8781 mL | 1.7561 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.
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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05371964 | Recruiting | Drug: Imetelstat Drug: Ruxolitinib |
Myelofibrosis | Geron Corporation | May 4, 2022 | Phase 1 |
| NCT05583552 | Recruiting | Drug: Imetelstat | Myelodysplastic Syndromes Acute Myeloid Leukemia |
GCP-Service International West GmbH |
June 5, 2023 | Phase 2 |
| NCT04576156 | Recruiting | Drug: Imetelstat Drug: Best Available Therapy (BAT) |
Myelofibrosis | Geron Corporation | April 12, 2021 | Phase 3 |
| NCT02598661 | Active Recruiting |
Drug: Imetelstat Drug: Placebo |
Myelodysplastic Syndromes | Geron Corporation | November 24, 2015 | Phase 2 Phase 3 |
| NCT00427349 | Completed | Drug: AMG 706 Drug: octreotide |
Islet Cell Tumor Neoplastic Syndrome |
Eastern Cooperative Oncology Group/td> | November 7, 2008 | Phase 2 |
Motesanib in vitro activity on VEGFR2 signaling and interaction with radiation. Clin Cancer Res. 2010 Jul 15;16(14):3639-47. |
Vascular distribution and tumor architecture in UM-SCC1 xenografts. Clin Cancer Res. 2010 Jul 15;16(14):3639-47. |
Impact of motesanib on intratumoral hypoxia (pimonidazole), proliferation (Ki67), and vasculature (9F1). Clin Cancer Res. 2010 Jul 15;16(14):3639-47. |
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