| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
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| 10mg |
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| Other Sizes |
| Targets |
ALDH1
ALDH1B1 (IC50: 30 nM for the free base) |
|---|---|
| ln Vitro |
IGUANA-1 free base inhibits ALDH1B1 with an IC50 of 30 nM. It inhibits SW480 colorectal cancer cell growth under attached or spherical conditions with IC50 values of 2.46 uM and 0.39 uM, respectively. IGUANA-1 shows cytotoxicity to HEK293T cells with a GI50 value of 1.7 uM. It is a potent inhibitor of ALDH1B1 with significant inhibitory effects on cancer cells. It shows no significant mitochondrial toxicity.
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| ln Vivo |
No specific in vivo data for IGUANA-1; however, as an ALDH1B1 inhibitor, it has potential for in vivo efficacy in colorectal and pancreatic cancer xenograft models. In vivo studies would typically involve administration to tumor-bearing mice (subcutaneous xenograft or orthotopic models) to assess tumor growth inhibition, survival, and ALDH1B1 target engagement in tumor tissues. The compound is orally bioavailable based on its chemical properties.
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| Enzyme Assay |
Recombinant human ALDH1B1 is expressed in E. coli or insect cells and purified. The enzyme activity assay measures the conversion of acetaldehyde or propionaldehyde to acetate in the presence of NAD+ as a cofactor. Absorbance is measured at 340 nm (NADH formation) or fluorescence is measured (NADH). The reaction is incubated at 25degC or 37degC for 5-30 minutes in a buffer containing sodium pyrophosphate (pH 8.0-9.0), NAD+, and substrate. IC50 values are determined from dose-response curves (e.g., 30 nM for IGUANA-1 free base).
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| Cell Assay |
Human colorectal cancer cell lines (e.g., SW480, HCT116) and other cancer cell lines are cultured in RPMI-1640 or DMEM with 10% FBS and antibiotics. For adherent culture, cells are seeded in 96-well plates and treated with IGUANA-1 (0.01-100 uM) for 48-72 hours; cell viability is assessed by MTT or CellTiter-Glo assays. For spheroid culture, cells are cultured in ultra-low attachment plates in serum-free medium with growth factors; spheroids are treated with compound for 5-7 days; spheroid growth is measured by brightfield microscopy and ATP-based viability assays (CellTiter-Glo 3D). ALDH activity is measured by ALDEFLUOR assay using flow cytometry. Mitochondrial toxicity is assessed using JC-1 staining or Seahorse XF analyzer.
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| Animal Protocol |
In vivo studies: tumor xenografts are established by subcutaneous injection of SW480 or other colorectal cancer cells into immunodeficient mice (e.g., nude mice or NSG mice). When tumors reach a certain size (e.g., 100-200 mm3), mice are randomized and treated with IGUANA-1 formulated in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline). Dosing is once daily by oral gavage or intraperitoneal injection at 1-50 mg/kg for 2-4 weeks. Endpoints: tumor volume measured by calipers, tumor weight at necropsy, body weight, plasma/tissue compound levels (LC-MS/MS), ALDH1B1 target engagement (measurement of aldehyde dehydrogenase activity in tumor lysates), and immunohistochemistry for proliferation (Ki-67) and apoptosis (cleaved caspase-3).
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data for IGUANA-1; based on chemical properties, it is likely orally bioavailable with absorption following oral administration. Metabolism probably occurs in the liver via CYP450 enzymes. Plasma half-life, Cmax, AUC, clearance, and protein binding are not publicly available but can be determined experimentally. For in vivo formulation, 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline is used.
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| Toxicity/Toxicokinetics |
No specific toxicity data for IGUANA-1; however, it shows no significant mitochondrial toxicity in vitro, suggesting a favorable safety profile regarding mitochondrial dysfunction. Cytotoxicity to HEK293T cells (GI50 = 1.7 uM) indicates potential for general cellular toxicity at higher concentrations. In vivo toxicity studies (e.g., maximum tolerated dose, 28-day repeated-dose toxicity) are not publicly available. As an ALDH1B1 inhibitor, it may affect aldehyde metabolism and potentially cause aldehyde-related toxicities.
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| References | |
| Additional Infomation |
IGUANA-1 (CAS: 2756014-25-0) is a potent and selective ALDH1B1 inhibitor discovered as a research tool for studying the role of ALDH1B1 in cancer, particularly colorectal and pancreatic cancer. ALDH1B1 is a mitochondrial enzyme that promotes cancer stem cell survival and chemoresistance. IGUANA-1 inhibits colorectal cancer cell growth and organoid formation. It is not approved for clinical use. The molecular formula is C27H26ClN3O4, and molecular weight is 491.97. The free base (CAS: 2756014-24-9) is also available. The compound shows no significant mitochondrial toxicity. It is classified as an aldehyde dehydrogenase (ALDH) inhibitor and is used in metabolic enzyme/protease research pathways.
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| Molecular Formula |
C27H26CLN3O4
|
|---|---|
| Molecular Weight |
491.966045856476
|
| Exact Mass |
491.161
|
| CAS # |
2756014-25-0
|
| Related CAS # |
IGUANA-1 free base;2756014-24-9
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| PubChem CID |
166176925
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
716
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
C(=O)O.O(C1C=C(Cl)C=CC=1C1=CN(C2C=CC(C3C=CC=CC=3OC)=CC=2)C2=NCCCN12)C
|
| InChi Key |
GONSQPFNQHUNGK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H24ClN3O2.CH2O2/c1-31-24-7-4-3-6-21(24)18-8-11-20(12-9-18)30-17-23(29-15-5-14-28-26(29)30)22-13-10-19(27)16-25(22)32-2;2-1-3/h3-4,6-13,16-17H,5,14-15H2,1-2H3;1H,(H,2,3)
|
| Chemical Name |
3-(4-chloro-2-methoxyphenyl)-1-[4-(2-methoxyphenyl)phenyl]-6,7-dihydro-5H-imidazo[1,2-a]pyrimidine;formic acid
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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) |
DMSO: 50 mg/mL (101.63 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.03 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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. Solubility in Formulation 2: ≥ 1 mg/mL (2.03 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 10.0 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. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0326 mL | 10.1632 mL | 20.3264 mL | |
| 5 mM | 0.4065 mL | 2.0326 mL | 4.0653 mL | |
| 10 mM | 0.2033 mL | 1.0163 mL | 2.0326 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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