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Purity: ≥98%
IDF-11774 (IDF11774) is a novel, potent, and orally bioavailable HIF-1α (hypoxia-inducible factor 1α) inhibitor with anticancer activity. It inhibits HIF-1α with an IC50 of 3.65 μM. HIF-1 is associated with poor prognoses and therapeutic resistance in cancer patients. IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells under hypoxic conditions. Moreover, IDF-11774 treatment suppressed angiogenesis of cancer cells by reducing the expression of HIF-1 target genes, reduced glucose uptake, thereby sensitizing cells to growth under low glucose conditions, and decreased the extracellular acidification rate (ECAR) and oxygen consumption rate of cancer cells. Metabolic profiling of IDF-11774-treated cells revealed low levels of NAD+, NADP+, and lactate, as well as of intermediates in glycolysis and the tricarboxylic acid cycle. In addition, elevated AMP and diminished ATP levels were observed, resulting in a high AMP/ATP ratio. The level of AMP-activated protein kinase phosphorylation also increased, leading to inhibition of mTOR signaling in treated cells. In vivo xenograft assays demonstrated that IDF-11774 exhibited substantial anticancer efficacy in mouse models containing KRAS, PTEN, or VHL mutations, which often occur in malignant cancers. Collectively, these data indicate that IDF-11774 suppressed hypoxia-induced HIF-1α accumulation and repressed tumor growth by targeting energy production-related cancer metabolism.
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| ln Vitro |
In cancer cell lines, IDF-11774 is a new inhibitor of hypoxia-inducible factor (HIF)-1, having an IC50 of 3.65 μM. A Phase I study has approved IDF-11774 as a therapeutic medication candidate. IDF-11774 treatment of human umbilical cord vascular endothelial cells (HUVEC) resulted in less capillary network development on Matrigel. Treatment with IDF-11774 led to a reduction in GLUT1 and pyruvate dehydrogenase kinase 1 (PDK1) mRNA expression. Moreover, intracellular ATP levels were considerably lowered when IDF-11774 was present, and the effects were more pronounced when low glucose levels (5.5 mM) were present [1].
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| ln Vivo |
When mice treated with oral IDF-11774 had tumors, luciferase activity and HIF-1α accumulation were significantly reduced in comparison to controls. Oral IDF-11774 treatment for two weeks resulted in significant dose-dependent tumor shrinkage in mice models [1].
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| References |
[1]. Ban HS, et al. The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth. Cell Death Dis. 2017 Jun 1;8(6):e2843
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| Molecular Formula |
C23H32N2O2
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| Molecular Weight |
368.512386322021
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| CAS # |
1429054-28-3
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| SMILES |
O=C(N1CCN(C)CC1)COC2=CC=C(C34C[C@H]5C[C@@](C4)([H])C[C@H](C5)C3)C=C2
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| InChi Key |
QGBBBLPWBSWERZ-KIOFGVERSA-N
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| InChi Code |
InChI=1S/C23H32N2O2/c1-24-6-8-25(9-7-24)22(26)16-27-21-4-2-20(3-5-21)23-13-17-10-18(14-23)12-19(11-17)15-23/h2-5,17-19H,6-16H2,1H3/t17-,18-,19-,23?
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| Chemical Name |
2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)-1-(4-methylpiperazin-1-yl)ethan-1-one
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| Synonyms |
IDF11774; IDF 11774; IDF-11774
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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) |
DMSO : ~60 mg/mL (~162.82 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.53 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 16.7 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. Solubility in Formulation 2: ≥ 1.67 mg/mL (4.53 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. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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: ≥ 1.67 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7136 mL | 13.5682 mL | 27.1363 mL | |
| 5 mM | 0.5427 mL | 2.7136 mL | 5.4273 mL | |
| 10 mM | 0.2714 mL | 1.3568 mL | 2.7136 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.
 Effect of IDF-11774 on energy metabolism.
Effect of IDF-11774 on glycolytic energy metabolism and cell growth.Cell Death Dis. 2017 Jun 1;8(6):e2843. |
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 Antitumor efficacy of IDF-11774 in HCT116 xenograft models.
Metabolic profile of cells treated with IDF-11774 under hypoxic conditions.Cell Death Dis. 2017 Jun 1;8(6):e2843. |
 IDF-11774 inhibits HIF-1αaccumulation in HCT116 cells.(a) Structure of IDF-11774 and its effect on HIF-1αaccumulation, as determined by western blot analysis. (b)In vivobioluminescence imaging of HIF-1 activity. (c) Quantitative real-time PCR analysis of the mRNA expression levels of HIF-1αtarget genes in HCT116 cells treated with IDF-11774 for 18 h. (d)In vitrotube formation: HUVECs were treated with DMSO, IDF-11774, or sunitinib under 1% O2for 24 h.Cell Death Dis. 2017 Jun 1;8(6):e2843. |
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