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Gigantol is an orally active bibenzyl compound. Gigantol targets MYC to promote its ubiquitin-proteasomal degradation and inhibit the growth of lung cancer cells. Gigantol exerts anti-lung cancer activity by inducing ferroptosis (Ferroptosis) via the SLC7A11-GPX4 axis. Gigantol restores the sensitivity of mcr-harboring multidrug-resistant bacteria to colistin. Gigantol ameliorates carbon tetrachloride-induced liver injury by inhibiting the activation of the JNK/cPLA2/12-LOX inflammatory pathway. Gigantol promotes cholesterol metabolism and progesterone biosynthesis in Leydig cells. Gigantol can be used in studies related to diseases such as lung cancer, multidrug-resistant Gram-negative bacterial infections, and acute liver injury.
For research use only. We do not sell to patients.
Gigantol is an orally active bibenzyl compound. Gigantol targets MYC to promote its ubiquitin-proteasomal degradation and inhibit the growth of lung cancer cells. Gigantol exerts anti-lung cancer activity by inducing ferroptosis (Ferroptosis) via the SLC7A11-GPX4 axis. Gigantol restores the sensitivity of mcr-harboring multidrug-resistant bacteria to colistin. Gigantol ameliorates carbon tetrachloride-induced liver injury by inhibiting the activation of the JNK/cPLA2/12-LOX inflammatory pathway. Gigantol promotes cholesterol metabolism and progesterone biosynthesis in Leydig cells. Gigantol can be used in studies related to diseases such as lung cancer, multidrug-resistant Gram-negative bacterial infections, and acute liver injury[1][2][3][4][5].
Cellular Effect
Cell Line
Type
Value
Description
References
A549
IC50
> 10 μM
Compound: 17
Cytotoxicity against human A549 cells assessed as decrease in cell viability after 6 days by MTT assay
Cytotoxicity against human A549 cells assessed as decrease in cell viability after 6 days by MTT assay
Antiinflammatory activity in human neutrophils assessed as inhibition of FMLP/cytochalasin B-induced superoxide anion generation by measuring superoxide dismutase-inhibitable reduction of ferricytochrome c preincubated for 5 mins followed by FMLP/cytochalasin B-induction by spectrophotometric analysis
Antiinflammatory activity in human neutrophils assessed as inhibition of FMLP/cytochalasin B-induced superoxide anion generation by measuring superoxide dismutase-inhibitable reduction of ferricytochrome c preincubated for 5 mins followed by FMLP/cytochalasin B-induction by spectrophotometric analysis
Antiinflammatory activity in human neutrophils assessed as inhibition of fMLP/CB-induced elastase release using MeO-Suc-Ala-Ala-Pro-Val-p-nitroanilide as elastase substrate preincubated for 5 mins followed by fMLP/CB-induction
Antiinflammatory activity in human neutrophils assessed as inhibition of fMLP/CB-induced elastase release using MeO-Suc-Ala-Ala-Pro-Val-p-nitroanilide as elastase substrate preincubated for 5 mins followed by fMLP/CB-induction
Gigantol (0-200 μM; 0-72 h) exhibits dose-dependent cytotoxicity and dose- and time-dependent antiproliferative effects against H460, A549 and H292 cells[1]. Gigantol (0-20 μM; 10 days) dose-dependently inhibits the colony-forming ability of H460, A549 and H292 cells[1]. Gigantol (5-20 μM; 24 h) dose-dependently downregulates MYC protein expression in human lung cancer cell lines H460, A549 and H292[1]. Gigantol (5-20 μM; 24 h) reduces the inactive phosphorylated Ser9 form of GSK3β in a dose-dependent manner (thereby enhancing GSK3β activity), without altering the total GSK3β levels in human lung cancer cell lines H460, A549 and H292[1]. Gigantol (20 μM; 15–90 min) significantly reduced the stability of MYC protein and shortened its half-life in H460, A549, and H292 human lung cancer cells when co-incubated with Cycloheximide (HY-12320) [1]. Gigantol (20 μM; 1 h) downregulates MYC expression and enhances the ubiquitination level of MYC in H460, A549 and H292 human lung cancer cells, whereas pretreatment with the proteasome inhibitor MG132 (HY-13259) reverses this effect, confirming that gigantol promotes proteasomal degradation of MYC[1]. Gigantol (50-150 μM; 24 h) dose-dependently increases the levels of ROS and Fe2+ in H460 and A549 human lung cancer cells, induces ferroptosis-related mitochondrial cristae loss, and reduces mitochondrial membrane potential in these cells[2]. Gigantol (50-150 μM; 24 h) dose-dependently enhances lipid peroxidation in human lung cancer cells H460 and A549[2]. Gigantol (50-150 μM; 24 h) reduces the protein expression levels of SLC7A11 and GPX4 in human lung cancer cells H460 and A549 in a dose-dependent manner[2]. Gigantol (50-150 μM; 24 h) reduces extracellular cystine uptake as well as intracellular cysteine and GSH levels, and increases intracellular glutamate and MDA levels in H460 and A549 human lung cancer cells[2]. Gigantol (32 μg/mL, serial dilution treatment; 18 h) exerts a synergistic effect with colistin to restore the sensitivity of colistin-resistant Gram-negative bacteria carrying the *mcr* gene (including *E. coli* B2, *Salmonella* 15E343 and *K. pneumoniae* 19-2-1) to colistin, with a FICI value ≤ 0.375. However, it does not enhance the activity of colistin against colistin-sensitive strains or *mcr*-negative strains[3]. Gigantol (10 μM; 4 h) upregulates genes associated with cholesterol and steroid biosynthesis/metabolism (Star, Lss, Idi1) in mouse MA-10 cells, increases lipid droplet accumulation in cells, and promotes progesterone production[5]. Gigantol (10-100 μM; 4 h) increases the basal StAR protein level and the transcriptional activity of AP-1 in mouse MA-10 Leydig cells[5]. Gigantol (100 μM; 4 h) reduces the viability of mouse MA-10 Leydig cells[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Caused significant dose-dependent toxic effects, reducing cell viability, at 50, 100, and 200 μM in all three cell lines. Caused no significant reduction in cell viability at 5, 10, and 20 μM in any of the tested cell lines.
Significantly reduced proliferation after 24 h in H460 and A549 cells at 20 μM. Significantly suppressed proliferation after 72 h in H460 and A549 cells at 5 and 10 μM. Significantly reduced proliferation after 48 h in H292 cells at all tested concentrations (5, 10, 20 μM).
Dose-dependently reduced MYC protein levels. Significantly reduced MYC levels in all three cell lines at 10 and 20 μM. Significantly reduced MYC levels in H460 and A549 cells at 5 μM. Dose-dependently reduced the level of inactive phosphorylated Ser9 GSK3β, with no significant effect on total GSK3β levels in all three cell lines. Significantly reduced the ratio of phosphorylated to total GSK3β in a dose-dependent manner, indicating increased GSK3β activity.
Significantly reduced MYC protein levels when administered alone. Induced MYC down-regulation that was reversed by pretreatment with 5-20 μM MG132 in all three cell lines.
Caused a concentration-dependent decrease in SLC7A11 and GPX4 protein expression in both H460 and A549 cells, with lower protein levels observed at higher concentrations compared to the control group.
Increased DCFH-DA and ferroOrange fluorescent expression. Decrease Mito-Tracker Red CMXRos fluorescent expression. Increased C11 BODIPY 581/591 fluorescent ratio expression. Caused a significant decrease in GPX4 fluorescence intensity in both H460 and A549 cells, indicating reduced GPX4 protein expression compared to the control group.
Increased Star gene expression in the absence of forskolin, and increased Lss gene expression. Showed a non-significant improvement in Nsdhl gene expression. Improved Idi1 gene expression in the presence of forskolin. Detected no significant changes in Fra2, Creb1, Mvd, Mvk, or Fdx1 gene expression.
Reduced cell viability relative to untreated controls at 100 μM. Detected no significant changes in viability at 1 or 10 μM.
In Vivo
Gigantol (30-60 mg/kg; i.p.; daily for 12 consecutive days) significantly reduces the volume and weight of lung tumors in BALB/c-nu mice without causing obvious in vivo toxicity[2]. Gigantol (40 mg/kg; p.o.; once daily for 7 consecutive days) significantly alleviates CCl4-induced acute liver injury and hepatic inflammation in male ICR mice by inhibiting the JNK/cPLA2/12-LOX pathway, reducing the infiltration and activation of proinflammatory immune cells, and restoring the levels of arachidonic acid metabolites[4]. Gigantol (40 mg/kg; i.v.; once every 12 hours, 3 times total) significantly alleviates liver ischemia-reperfusion injury in male C57 mice by improving liver function and reducing pathological damage[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
BALB/c-nu (female, subcutaneous H460 lung cancer tumor model)[2]
Dosage:
30 mg/kg; 60 mg/kg
Administration:
i.p.; daily; 12 days
Result:
Significantly inhibited tumor volume and tumor weight relative to the control group. Showed no significant differences in mouse body weight relative to the control group. Induced no apparent treatment-related toxicity in heart, liver, spleen, lung, and kidney tissues (confirmed via hematoxylin-eosin staining).
Reversed the CCl4-induced elevation of serum ALT and AST levels. Reduced centrilobular necrosis, swelling, steatosis, and inflammatory infiltration in liver histology. Decreased the proportion of M1 macrophages (CD86+/F4/80+) from 38.1% to 16.3%, and the proportion of neutrophil infiltration (CD11b+/Ly6G+) from 21.7% to 9.94%. Inhibited the CCl4-induced elevation of p-JNK/JNK protein ratio, p-cPLA2/cPLA2 protein ratio, and PLA2 mRNA expression in liver tissue. Reversed the CCl4-induced elevation of multiple hepatic arachidonic acid metabolites, particularly significantly reducing 12-HETE levels from 6.67-fold to 2.85-fold in the control group, while also reducing the levels of 11-HETE, 8-HETE, 5,6-DHET, and 8,9-DHET. Significantly reduced the CCl4-induced increase in the expression levels of Alox12 and Alox15 mRNA in the liver, and reduced the protein expression of platelet- and leukocyte-type 12-lipoxygenase (12-LOX) in liver tissue.
Animal Model:
C57 (male, 22-25 g, hepatic ischemia-reperfusion injury induced by 70% warm hepatic ischemia for 1 hour followed by 6 hours of reperfusion)[4]
Dosage:
40 mg/kg
Administration:
i.v.; 3 times at 12-hour intervals
Result:
Reduced serum ALT and AST levels. Improved liver histopathological changes (reduced centrilobular necrosis, tumefaction, and inflammatory infiltration) compared to the ischemia-reperfusion injury group.
Room temperature in continental US; may vary elsewhere.
Storage
Pure form
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (182.28 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
3.6455 mL
18.2276 mL
36.4551 mL
5 mM
0.7291 mL
3.6455 mL
7.2910 mL
10 mM
0.3646 mL
1.8228 mL
3.6455 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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