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| Targets |
Galectin-1 (Gal1). OTX008 is a selective inhibitor of galectin-1. Galectin-1 is a β-galactoside-binding protein that plays a critical role in cell adhesion, migration, proliferation, and apoptosis. It is overexpressed in various cancers and contributes to tumor progression, angiogenesis, and immune evasion. OTX008 binds to the amphipathic β-sheet conformation of galectin-1. Upon administration, OTX008 binds Gal-1 which leads to Gal-1 oxidation and proteasomal degradation, through an as of yet not fully elucidated mechanism, and eventually downregulation of Gal-1. By inhibiting Gal-1, OTX008 affects endothelial cell proliferation, motility, invasiveness, and cord formation. The compound has potential anti-angiogenic and antineoplastic activities.
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| ln Vitro |
OTX008's growth inhibitory concentration (GI50) spans from 3 to 500 μM in a variety of human solid tumor cell lines. In the mold group, there was a strong association found between the levels of protein expression and Gal1 mRNA (LGALS1) and OTX008 GI50 values. OTX008 stimulates G2/M cell cycle signaling through CDK1 and suppresses Gal1 expression as well as ERK1/2- and AKT-dependent survival pathways in SQ20B and A2780-1A9 cells. OTX008 inhibits head formation brought on by exogenous Gal1 and strengthens the anti-apoptotic action of semaphorin-3A (Sema3A) in SQ20B cells [1]. OTX008 has an impact on the shortest, motility, proliferation, and umbilical cord of endothelial cells. Additionally, variations in gravity between cell lines (IC50: 1-190 μM) prevent tumor growth [2].
OTX008 demonstrates potent anti-tumoural activity in vitro. It is a selective inhibitor of galectin-1 (Gal1). OTX008 inhibits SQ20B and A2780-1A9 cells by inhibiting Gal1 expression and ERK1/2 and AKT-dependent survival pathways. It triggers G2/M cell cycle arrest through CDK1. The compound enhances the anti-proliferative effect of Semaphorin-3A in SQ20B cells and reverses invasion caused by exogenous Gal1. OTX008 affected endothelial cell proliferation, motility, invasiveness, and cord formation. The compound's anti-angiogenic and antineoplastic activities have been demonstrated in various in vitro models. |
| ln Vivo |
The growth of subcutaneously transplanted A2780-1A9 tumors is transcribed by OTX008. OTX008 decreases blood vessel density and transcriptionally controls the expression of Gal1, Ki67, and VEGFR2. When OTX008 was initially introduced, it showed promise in terms of jump treatment and cell multiple toxicity [1].
OTX008 has been studied in vivo for its anti-tumoural and anti-angiogenic effects. The compound has potential anti-angiogenic and antineoplastic activities. Upon subcutaneous administration, OTX008 binds Gal-1 which leads to Gal-1 oxidation and proteasomal degradation, and eventually downregulation of Gal-1. The compound's effects on tumor growth and angiogenesis have been evaluated in preclinical models. Detailed in vivo pharmacokinetic and pharmacodynamic data are limited in publicly available sources. OTX008 is for research use only and is not for human therapeutic use. |
| Enzyme Assay |
Galectin-1 binding assays are performed using recombinant galectin-1 protein. The compound's binding affinity for galectin-1 is assessed using surface plasmon resonance (SPR) or fluorescence polarization assays. OTX008 binds to the amphipathic β-sheet conformation of galectin-1. Alternatively, pull-down assays using immobilized OTX008 can be used to assess binding to galectin-1 from cell lysates. The compound's selectivity for galectin-1 over other galectins is assessed using similar binding assays with recombinant proteins. The compound's ability to inhibit galectin-1 function can be assessed by measuring its effects on endothelial cell proliferation, motility, invasiveness, and cord formation.
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| Cell Assay |
Cellular galectin-1 inhibition is evaluated in cancer cell lines, including SQ20B and A2780-1A9 cells. Cells are cultured in appropriate media at 37°C with 5% CO₂ and treated with OTX008 at various concentrations for 24-72 hours. Galectin-1 expression is assessed by Western blotting. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. Apoptosis is evaluated by Annexin V/PI staining and caspase-3/7 activity assays. Endothelial cell tube formation assays are used to assess anti-angiogenic effects. Each experiment includes vehicle controls and appropriate positive controls to validate the assay systems.
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| Animal Protocol |
In vivo efficacy of OTX008 is evaluated in mouse xenograft models using human cancer cell lines. Tumor cells are implanted subcutaneously in immunodeficient mice. When tumors reach a predetermined size, mice are randomized into treatment and control groups. OTX008 is administered subcutaneously at doses determined by preclinical studies. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis, immunohistochemistry (Ki67 for proliferation, CD31 for angiogenesis), and biochemical assays (Gal-1 expression). Body weight and clinical signs are monitored throughout the study to assess tolerability. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 937.18. Formula: Not fully specified. CAS No.: 286936-40-1. Synonyms: Calixarene 0118, PTX008. Appearance: Solid. Purity: Typically 99.09%. Solubility: DMSO: 3 mg/mL (3.2 mM); Ethanol: 25 mg/mL. Water: Insoluble. In vivo: Homogeneous suspension in CMC-NA at ≥5 mg/mL. Storage: Typically at -20°C. OTX008 is a selective inhibitor of galectin-1 with anti-tumoural activity.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for OTX008. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As a galectin-1 inhibitor, potential toxicities may include effects on cell adhesion, migration, and immune function. Standard toxicity studies would include acute toxicity assessment in rodents, repeated dose toxicity studies (14-day and 28-day), and genotoxicity screening (Ames test, micronucleus assay). The compound is for research use only and not for human therapeutic use.
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| References |
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| Additional Infomation |
OTX008 has been used in clinical trials for the treatment of solid tumors. OTX008, a galactolectin-1 inhibitor, is a calixarene-based compound and a galactolectin-1 (Gal-1) inhibitor with potential anti-angiogenic and anti-tumor activity. After subcutaneous injection, OTX008 binds to Gal-1, leading to Gal-1 oxidation and proteasome degradation (the mechanism of which is not fully elucidated), ultimately resulting in downregulation of Gal-1 expression. This reduces tumor cell growth and inhibits angiogenesis. Gal-1 is a multifunctional carbohydrate-binding protein that is typically overexpressed on tumor cells and plays a crucial role in cancer cell proliferation, apoptosis, tumor angiogenesis, and immune escape.
OTX008 is also known as Calixarene 0118, PTX008. Its IUPAC name is not fully resolved in publicly available sources. OTX008 is a selective inhibitor of galectin-1 with anti-tumoural activity. It affects endothelial cell proliferation, motility, invasiveness, and cord formation. OTX008 inhibits SQ20B and A2780-1A9 cells by inhibiting Gal1 expression and ERK1/2 and AKT-dependent survival pathways, and triggers G2/M cell cycle arrest through CDK1. No clinical trials have been reported for this compound. OTX008 is for research use only. |
| Molecular Formula |
C52H72N8O8
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|---|---|
| Molecular Weight |
937.18
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| Exact Mass |
936.547
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| CAS # |
286936-40-1
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| PubChem CID |
11953346
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
1143.4±65.0 °C at 760 mmHg
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| Flash Point |
645.3±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.569
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| LogP |
4.14
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
68
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| Complexity |
1250
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CQVAQQNDZCZBSU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C52H72N8O8/c1-57(2)25-21-53-45(61)33-65-49-37-13-9-14-38(49)30-40-16-11-18-42(51(40)67-35-47(63)55-23-27-59(5)6)32-44-20-12-19-43(52(44)68-36-48(64)56-24-28-60(7)8)31-41-17-10-15-39(29-37)50(41)66-34-46(62)54-22-26-58(3)4/h9-20H,21-36H2,1-8H3,(H,53,61)(H,54,62)(H,55,63)(H,56,64)
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| Chemical Name |
N-[2-(dimethylamino)ethyl]-2-[[26,27,28-tris[2-[2-(dimethylamino)ethylamino]-2-oxoethoxy]-25-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaenyl]oxy]acetamide
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| Synonyms |
OTX008; OTX 008; OTX-008
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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 |
| 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) |
Ethanol : ~33.33 mg/mL (~35.56 mM)
DMSO : ~5 mg/mL (~5.34 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (1.33 mM) (saturation unknown) in 10% EtOH + 90% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.5 mg/mL (0.53 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 5.0 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: ≥ 0.5 mg/mL (0.53 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: ≥ 0.5 mg/mL (0.53 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 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 5: 0.5 mg/mL (0.53 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0670 mL | 5.3352 mL | 10.6703 mL | |
| 5 mM | 0.2134 mL | 1.0670 mL | 2.1341 mL | |
| 10 mM | 0.1067 mL | 0.5335 mL | 1.0670 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.
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