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ISO-1

Alias: ISO-1 ISO 1 ISO1 MIF Antagonist Macrophage Migration Inhibitory Factor
Cat No.:V9770 Purity: ≥98%
ISO-1, formerly known as MIF Antagonist and ISO-1 and Macrophage Migration Inhibitory Factor, is a MIF inhibitor.
ISO-1
ISO-1 Chemical Structure CAS No.: 478336-92-4
Product category: MIF
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

ISO-1, formerly known as MIF Antagonist and ISO-1 and Macrophage Migration Inhibitory Factor, is a MIF inhibitor. ISO-1 has CAS#478336-92-4. INVIVO-6924 Protects Photoreceptors and Reduces Gliosis in Experimental Retinal Detachment. Systemic administration of the MIF inhibitor ISO-1 significantly blocked photoreceptor apoptosis, outer nuclear layer (ONL) thinning, and retinal gliosis. ISO-1 and MIF knockout (MIFKO) had greater accumulation of Müller glia pERK expression in the detached retina, suggesting that Müller survival pathways might underlie the neuroprotective response.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
Without recombinant MIF added, ISO-1 (0.1–20 μM; 16 hours) has a mild inhibitory effect on Cox-2 secretion [1].
ln Vivo
ISO-1 (ip; 3.5–35 mg/kg; twice daily; 2 weeks) has anti-inflammatory properties and increases survival from lethal endotoxemia [2]. Intraperitoneal injection ISO-1 (35 mg/kg, twice daily, 3 days) significantly lowers Flk1 expression in the implants and decreases mean implant size [3].
Cell Assay
Western Blot Analysis[1]
Cell Types: RAW 264.7 macrophages
Tested Concentrations: 0.1μM, 1μM, 10μM, 20μM
Incubation Duration: 16 hrs (hours)
Experimental Results: Inhibition of Cox-2 secretion.
Animal Protocol
Animal/Disease Models: C57Bl/6 MIF+/+ and MIF–/– mice [2]
Doses: 3.5-35 mg/kg
Route of Administration: intraperitoneal (ip) injection; 3.5-35 mg/kg; twice (two times) daily; 2 weeks
Experimental Results: Yes Preventing fatal sepsis.

Animal/Disease Models: Female C57BL/6-Tg(ACTB-EGFP)1Osb/J mice [3]
Doses: 35 mg/kg
Route of Administration: intraperitoneal (ip) injection; 35 mg/kg; twice (two times) daily; 3 days
Experimental Results: In utero The average size of the endometriotic implants diminished.
References

[1]. The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents. J Biol Chem. 2002 Jul 12;277(28):24976-82.

[2]. ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis. J Biol Chem. 2005 Nov 4;280(44):36541-4.

[3]. Inhibition of macrophage migration inhibitory factor reduces endometriotic implant size in mice with experimentally induced disease. J Endometr. 2011 Sep 30;3(3):135-142.

Additional Infomation
5-Isoxazoleacetic acid, 4,5-dihydro-3-(4-hydroxyphenyl)-, methyl ester is a member of phenols.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C12H13NO4
Molecular Weight
235.239
Exact Mass
235.084
CAS #
478336-92-4
Related CAS #
478336-92-4;
PubChem CID
4633677
Appearance
White to off-white solid powder
Density
1.3±0.1 g/cm3
Boiling Point
365.0±48.0 °C at 760 mmHg
Melting Point
114 °C
Flash Point
174.6±29.6 °C
Vapour Pressure
0.0±0.8 mmHg at 25°C
Index of Refraction
1.582
LogP
0.89
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
5
Rotatable Bond Count
4
Heavy Atom Count
17
Complexity
308
Defined Atom Stereocenter Count
0
InChi Key
AIXMJTYHQHQJLU-UHFFFAOYSA-N
InChi Code
InChI=1S/C12H13NO4/c1-16-12(15)7-10-6-11(13-17-10)8-2-4-9(14)5-3-8/h2-5,10,14H,6-7H2,1H3
Chemical Name
4,5-dihydro-3-(4-hydroxyphenyl)-5-isoxazoleacetic acid, methyl ester
Synonyms
ISO-1 ISO 1 ISO1 MIF Antagonist Macrophage Migration Inhibitory Factor
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 : ~50 mg/mL (~212.55 mM)
Solubility (In Vivo)
Solubility in Formulation 1: 5 mg/mL (21.25 mM) in 5% DMSO + 95% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (10.63 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.63 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.
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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.


Solubility in Formulation 4: ≥ 2.5 mg/mL (10.63 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 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 4.2510 mL 21.2549 mL 42.5098 mL
5 mM 0.8502 mL 4.2510 mL 8.5020 mL
10 mM 0.4251 mL 2.1255 mL 4.2510 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.

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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?
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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:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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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.)
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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
NCT02284919 ACTIVE, NOT RECRUITING Drug: [18F]ISO-1 Breast Cancer
Breast Neoplasm
University of Pennsylvania 2014-11 Phase 1
NCT00968656 COMPLETED Radiation: PET/CT
Other: Laboratory Testing
Other: Safety Testing
Breast Cancer
Diffuse Large B-cell Lymphoma
Head and Neck Cancer
Washington University School of Medicine 2009-01 Phase 1
NCT02204202 TERMINATED Drug: [18F]FDG
Drug: [18F]ISO-1
Lung Disease Washington University School of Medicine 2014-02
NCT03057743 TERMINATED Device: Positron emission tomography (PET/CT) imaging
Device: radiotracer [18F]ISO-1
METASTATIC BREAST CANCER Abramson Cancer Center at Penn Medicine 2016-04-05
NCT04831892 COMPLETED Other: Moisturizer Containing Isosorbide
Diesters and Colloidal Oatmeal
Other: Moisturizer containing Colloidal Oatmeal only
Atopic Dermatitis Integrative Skin Science and Research 2021-04-12 Not Applicable
Biological Data
  • The MIF inhibitor, ISO-1 reduces endometriotic implant mass. Endometriosis was induced and mice were subsequently treated as described in Materials and Methods. Average endometriotic implant size (mm3) was calculated between treatment groups. Data are displayed as the mean ± SD and are representative of 10 mice per treatment group (N=10). Data was analyzed by unpaired t-tests. Significance was set at p < 0.05 for all comparisons. Asterisks (*) indicates statistical significantly different means. Broken line indicates size of implants at start of experiment (1 mm3).[3]. Nothnick WB, et al. Inhibition of macrophage migration inhibitory factor reduces endometriotic implant size in mice with experimentally induced disease. J Endometr. 2011 Sep 30;3(3):135-142.
  • ISO-1 induced endometriotic implant regression is associated with reduced expression of the VEGF receptor, Flk1. Endometriosis was induced and mice were subsequently treated as described in Materials and Methods. Endometriotic implants were harvested after measurement and prepared for RNA isolation. Flk1 transcript levels were quantitated as described in Materials and Methods by qRT-PCR and normalized to 18S rRNA levels. Data are displayed as the mean ± SD and are representative of 6 independent samples per time point per treatment (N=6). Data was analyzed by unpaired t-tests. Significance was set at p < 0.05 for all comparisons. Asterisks (*) indicates statistical significantly different means.[3]. Nothnick WB, et al. Inhibition of macrophage migration inhibitory factor reduces endometriotic implant size in mice with experimentally induced disease. J Endometr. 2011 Sep 30;3(3):135-142.
  • ISO-1 induced regression of endometriotic implant mass is associated with reduced peritoneal fluid MIF activity. Peritoneal fluid was obtained from mice treated with vehicle or ISO-1and MIF activity was determined as described under Materials and Methods. Data are displayed as the mean ± SD and are representative of 9 independent samples per time point per treatment (N=9). Data was analyzed by unpaired t-tests. Significance was set at p < 0.05 for all comparisons. Asterisks (*) indicates statistical significantly different means. One sample was lost during the aspiration process.[3]. Nothnick WB, et al. Inhibition of macrophage migration inhibitory factor reduces endometriotic implant size in mice with experimentally induced disease. J Endometr. 2011 Sep 30;3(3):135-142.
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