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ISO-1 (Synonyms: ISO1, Macrophage Migration Inhibitory Factor)

Catalog No.GC17108 Copy One-Click Copy Product Info

ISO-1 is a cell-permeable isoxazoline class macrophage migration inhibitory factor (MIF) antagonist (IC50=7μM).

Products are for research use only. Not for human use. We do not sell to patients.

ISO-1 Chemical Structure

Cas No.: 478336-92-4

Size Price Stock Qty
10mM (in 1mL DMSO)
$71.00
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1mg
$42.00
In stock
5mg
$65.00
In stock
10mg
$104.00
In stock
50mg
$310.00
In stock
100mg
$497.00
In stock

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Sample solution is provided at 25 µL, 10mM.



Description of ISO-1

ISO-1 is a cell-permeable isoxazoline class macrophage migration inhibitory factor (MIF) antagonist (IC50=7μM). ISO-1 binds to the catalytic active site of MIF and inhibits its D-dopachrome tautomerase activity, and down-regulates the production of TNFα, PGE2 and COX-2 in human monocytes. ISO-1 can be used for related research on sepsis, immune inflammatory diabetes, asthma airway remodeling, experimental autoimmune uveoretinitis, retinal detachment, pancreatic cancer and colorectal cancer[1-4].

In vitro, treatment of gallbladder cancer cells with 0-500µM ISO-1 for 48 hours decreased cell viability, and reduced colony formation ability and invasive ability[5]. Pretreatment with 7µM ISO-1 for 1 hour improved the survival rate of PC12 cells exposed to β-amyloid 1-40, reduced detached cells and cell debris, and promoted the extension and increase of neurite-like processes[6]. Treatment of PANC-1 human pancreatic cancer cells with 200-3200µM ISO-1 for 48-96 hours inhibited cell proliferation, inhibited cell migration, and down-regulated the mRNA expression of MIF, NF-κB p65 and TNF-α[7].

In vivo, a single intraperitoneal injection of 3mg/kg ISO-1 in perioperative ischemic stroke (PIS) mice 2 hours before distal middle cerebral artery occlusion (dMCAO) reduced infarct volume, decreased IgG extravasation, restored tight junction protein ZO-1 expression, and improved Garcia neurological function scores[8]. Intraperitoneal injection of 35mg/kg ISO-1 for 6 consecutive weeks in ovalbumin-sensitized and challenged C57BL/6 mice reduced eosinophils, lymphocytes and total cell counts in bronchoalveolar lavage fluid, decreased lung tissue inflammatory cell infiltration, reduced airway wall area, alleviated airway smooth muscle hypertrophy, decreased subepithelial collagen deposition, and reduced goblet cell hyperplasia[9]. Intraperitoneal injection of 35mg/kg ISO-1 twice daily for 3 consecutive days starting 24 hours after cecal ligation and puncture in BALB/c mice increased the survival rate of mice with polymicrobial sepsis[10].

References:

[1] Ji W, Ren Y, Wei X, et al. Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway. Sci Rep. 2023 Feb 16;13(1):2788.

[2] Al-Abed Y, VanPatten S. MIF as a disease target: ISO-1 as a proof-of-concept therapeutic. Future Med Chem. 2011 Jan;3(1):45-63.

[3] Liu Y, Liu Y, Wang Q, et al. MIF inhibitor ISO-1 alleviates severe acute pancreatitis-associated acute kidney injury by suppressing the NLRP3 inflammasome signaling pathway. Int Immunopharmacol. 2021 Jul;96:107555.

[4] Li T, Qu J, Hu C, et al. Macrophage migration inhibitory factor (MIF) suppresses mitophagy through disturbing the protein interaction of PINK1-Parkin in sepsis-associated acute kidney injury. Cell Death Dis. 2024 Jul 2;15(7):473.

[5] Subbannayya T, Leal-Rojas P, Barbhuiya MA, et al. Macrophage migration inhibitory factor- a therapeutic target in gallbladder cancer. BMC Cancer. 2015 Nov 4;15:843.

[6] Yu M, Zang D, Xu Y, et al. Protective effect of ISO-1 against advanced glycation end product aggravation of PC12 cell injury induced by Aβ1-40. Mol Med Rep. 2019;20(3):2135-2142.

[7] Cheng B, Wang Q, Song Y, et al. MIF inhibitor, ISO-1, attenuates human pancreatic cancer cell proliferation, migration and invasion in vitro, and suppresses xenograft tumour growth in vivo. Sci Rep. 2020 Apr 21;10:6741.

[8] Li Y, Zou C, Chen C, et al. Myeloid-derived MIF drives RIPK1-mediated cerebrovascular endothelial cell death to exacerbate ischemic brain injury. Proc Natl Acad Sci U S A. 2023 Jan 24;120(5):e2219091120.

[9] Chen PF, Luo YL, Wang W, et al. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma. Mol Med. 2010 Sep-Oct;16(9-10):400-408.

[10] Al-Abed Y, Dabideen D, Aljabari B, et al. 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):36541-36544.

Protocol of ISO-1

Cell experiment [1]:

Cell lines

OCUG-1, NOZ, GB-d1, TGBC24TKB, TGBC2TKB, SNU-308, G-415 (human gallbladder cancer cell lines)

Preparation Method

Gallbladder cancer cells were seeded in 96-well plates or 6-well plates and treated with ISO-1 at 0 to 500μM for 48 hours, followed by MTT assay for cell viability, colony formation assay for 14 days, and transwell Matrigel invasion assay for 48 hours.

Reaction Conditions

0-500μM; 48h

Applications

ISO-1 decreased cell viability of gallbladder cancer cells, reduced colony forming ability, and decreased invasive ability through Matrigel.
Animal experiment [2]:

Animal models

Male Balb/C mice

Preparation Method

Mice were induced with endotoxemia by intraperitoneal injection of a sublethal dose of LPS (5mg/kg), and received intraperitoneal injections of ISO-1 at 3.5-35mg/kg 30 minutes before and 6 hours after LPS, then twice daily for 3 days; survival was monitored for 2 weeks. Separately, mice underwent cecal ligation and puncture (CLP) surgery, and received intraperitoneal injections of 35mg/kg ISO-1 starting 24 hours after CLP and twice daily for 3 days; survival was monitored for 2 weeks.

Dosage form

3.5-35mg/kg; i.p.; 30min before and 6h after LPS then twice daily for 3 days (endotoxemia)

35mg/kg; i.p.; starting 24h after CLP twice daily for 3 days (CLP sepsis)

Applications

ISO-1 dose-dependently improved survival of endotoxemic mice, and ISO-1 increased survival of CLP-induced polymicrobial septic mice.

References:

[1] Subbannayya T, Leal-Rojas P, Barbhuiya MA, et al. Macrophage migration inhibitory factor- a therapeutic target in gallbladder cancer. BMC Cancer. 2015 Nov 4;15:843.

[2] Al-Abed Y, Dabideen D, Aljabari B, et al. 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):36541-36544.

Chemical Properties of ISO-1

Cas No. 478336-92-4 SDF
Synonyms ISO1, Macrophage Migration Inhibitory Factor
Formula C12H13NO4 M.Wt 235.24
Solubility DMF: 20 mg/ml,DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml,DMSO: 14 mg/ml,Ethanol: 5 mg/ml Storage Store at -20°C
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table of ISO-1

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1 mg 5 mg 10 mg
1 mM 4.251 mL 21.2549 mL 42.5098 mL
5 mM 850.2 μL 4.251 mL 8.502 mL
10 mM 425.1 μL 2.1255 mL 4.251 mL
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3. All of the above co-solvents are available for purchase on the GlpBio website.

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Review for ISO-1

Average Rating: 5 ★★★★★ (Based on Reviews and 14 reference(s) in Google Scholar.)

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