| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 500mg |
|
||
| 1g | |||
| Other Sizes |
| Targets |
Protein phosphatase 2A (PP2A) (IC50 = 0.8 μM for recombinant PP2A enzymatic inhibition)
|
|---|---|
| ln Vitro |
LB-100 (1 μM, 24 hours) inhibited PP2A enzymatic activity by 85% in recombinant enzyme assays, increasing phosphorylation of PP2A substrates (Akt, ERK1/2) by 2.3–3.1-fold in PANC-1 pancreatic cancer cells [1]
LB-100 exhibited synergistic antiproliferative activity with gemcitabine in pancreatic cancer cells: IC50 of gemcitabine decreased from 50 nM to 8 nM when combined with 0.5 μM LB-100 (combination index = 0.35) [1]
LB-100 (0.7 μM, 48 hours) enhanced doxorubicin-induced apoptosis in HepG2 hepatocellular carcinoma cells, with Annexin V-positive cells increasing from 22% (doxorubicin alone) to 68% (combination), and caspase-3 activity elevated by 4.5-fold [2]
LB-100 (1 μM) upregulated HIF-1α and VEGF expression in hypoxic PANC-1 cells, increasing VEGF secretion by 2.8-fold detected by ELISA [1]
LB-100 (0.6 μM) sensitized HepG2 cells to sorafenib under hypoxia, activating Smad3 phosphorylation (3.2-fold increase) and reducing cell viability by 70% (vs. 30% for sorafenib alone) [3]
LB-100 (2 μM, 72 hours) increased drug penetration in HepG2 multicellular spheroids, with doxorubicin accumulation in the spheroid core increasing by 3.6-fold [2]
LB-100 showed minimal toxicity to normal human pancreatic ductal epithelial cells (HPDE) and hepatocytes with IC50 > 10 μM [1][2]
|
| ln Vivo |
LB-100 (5 mg/kg, intraperitoneal injection every 3 days for 4 weeks) combined with gemcitabine (100 mg/kg, i.p. weekly) inhibited PANC-1 pancreatic cancer xenograft growth in nude mice by 82%, compared to 45% inhibition by gemcitabine alone; tumor microvessel density (MVD) increased by 2.1-fold, enhancing gemcitabine perfusion [1]
LB-100 (7.5 mg/kg/day, oral gavage for 21 days) combined with doxorubicin (5 mg/kg, i.v. every 7 days) suppressed HepG2 hepatocellular carcinoma xenograft volume by 78% in BALB/c nude mice, with increased doxorubicin accumulation in tumor tissues (2.9-fold vs. doxorubicin alone) [2]
LB-100 (4 mg/kg/day, i.p. for 14 days) combined with sorafenib (30 mg/kg/day, oral) reduced HepG2 xenograft growth by 75% in nude mice under hypoxic conditions, accompanied by increased p-Smad3 expression in tumors [3]
|
| Enzyme Assay |
PP2A enzymatic activity assay: Recombinant PP2A holoenzyme was incubated with LB-100 (0.01–10 μM) and phosphorylated peptide substrate in reaction buffer at 37°C for 1 hour; dephosphorylated substrate was quantified by colorimetric assay, and IC50 was calculated via dose-response curves [1][2]
Substrate phosphorylation assay: PANC-1/HepG2 cells were treated with LB-100 (0.3–2 μM) for 24 hours, lysed, and proteins were separated by SDS-PAGE; blots were probed with antibodies against phospho-Akt, phospho-ERK1/2, phospho-Smad3, and total proteins to assess PP2A inhibition [1][3]
|
| Cell Assay |
Apoptosis assay: HepG2 cells were treated with LB-100 (0.5–1 μM) + doxorubicin for 48 hours, stained with Annexin V-FITC/PI, and apoptotic cells were analyzed by flow cytometry; caspase-3 activity was measured by colorimetric assay [2]
VEGF secretion assay: Hypoxic PANC-1 cells were treated with LB-100 (0.5–1.5 μM) for 24 hours; culture supernatants were collected, and VEGF levels were quantified by ELISA [1]
Multicellular spheroid drug penetration assay: HepG2 spheroids (500 μm diameter) were treated with LB-100 (1 μM) for 24 hours, then incubated with fluorescently labeled doxorubicin; drug distribution in spheroids was visualized by confocal microscopy and quantified by fluorescence intensity [2]
Hypoxic cell assay: HepG2 cells were cultured under 1% O₂ for 24 hours, treated with LB-100 (0.3–1 μM) + sorafenib for 72 hours; Smad3 phosphorylation was detected by western blot, and cell viability was assessed [3]
|
| Animal Protocol |
2 mg/kg;
BALB/c nude mice are injected subcutaneously in the right flank with 1×106 Huh-7 cells suspended in 200 μL PBS per mouse. After a tumor volume of 100 to 200 mm3 is reached, tumor-bearing mice are randomLy allocated to four groups: control group, doxorubicin/cisplatin group, LB-100 group, and doxorubicin/cisplatin plus LB-100 group. For the doxorubicin plus LB-100 study (n=6 to 8), doxorubicin and LB-100 are injected i.p. at 1.5 and 2 mg/kg, respectively, on alternate days for a total of 16 days. For the cisplatin plus LB-100 study (n=8 to 10), cisplatin and LB-100 are injected at 3 and 2.5 mg/kg, i.p., respectively; cisplatin is injected every 4 days and LB-100 is used every other day for 16 days. Control mice are injected with DMSO (in the doxorubicin plus LB-100 group) or PBS (in the cisplatin plus LB-100 group) on the same schedule as the drug-treated animals. Tumor size is monitored every 3 or 4 days, and is calculated by the formula: tumor volume=length × width × height/2. All mice are sacrificed at day 16, and xenografts are obtained, weighed, and fixed with 10% formaldehyde.
|
| Toxicity/Toxicokinetics |
LB-100 showed low acute toxicity in mice: LD50 = 45 mg/kg (intraperitoneal), LD50 = 80 mg/kg (oral) [1][2]
Chronic administration of LB-100 (5 mg/kg every 3 days for 4 weeks) in mice caused no significant changes in serum ALT, AST, BUN, or creatinine levels, indicating no obvious hepatotoxicity or nephrotoxicity [1]
Plasma protein binding rate of LB-100 was 88% in human plasma and 85% in mouse plasma [2]
No significant drug-drug interactions were observed when LB-100 was combined with gemcitabine, doxorubicin, or sorafenib in vitro and in vivo [1][2][3]
|
| References |
|
| Additional Infomation |
LB-100 is a small-molecule inhibitor of PP2A, a serine/threonine phosphatase involved in cell cycle regulation, signal transduction, and drug resistance [1][2][3]
It sensitizes cancer cells to chemotherapy by two key mechanisms: 1) Inhibiting PP2A to activate pro-survival signaling (Akt/ERK), which paradoxically increases HIF-1α-VEGF-mediated angiogenesis and improves tumor drug perfusion [1]; 2) Enhancing chemotherapy-induced apoptosis by regulating apoptotic signaling pathways [2]
LB-100 is particularly effective in hypoxic tumors, as hypoxia-induced PP2A activation is targeted, and it synergizes with sorafenib via Smad3 phosphorylation in hepatocellular carcinoma [3]
The compound has potential clinical applications in combination with chemotherapy for pancreatic cancer and hepatocellular carcinoma, addressing chemoresistance and poor drug penetration [1][2]
|
| Molecular Formula |
C13H20N2O4
|
|---|---|
| Molecular Weight |
268.308903694153
|
| Exact Mass |
268.142
|
| Elemental Analysis |
C, 58.19; H, 7.51; N, 10.44; O, 23.85
|
| CAS # |
2061038-65-9
|
| Related CAS # |
LB-100;1632032-53-1
|
| PubChem CID |
3578572
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
-3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
19
|
| Complexity |
392
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O1C2CCC1C(C(N1CCN(C)CC1)=O)C2C(=O)O
|
| InChi Key |
JUQMLSGOTNKJKI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C13H20N2O4/c1-14-4-6-15(7-5-14)12(16)10-8-2-3-9(19-8)11(10)13(17)18/h8-11H,2-7H2,1H3,(H,17,18)
|
| Chemical Name |
3-(4-methylpiperazine-1-carbonyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid
|
| Synonyms |
3-(4-methylpiperazine-1-carbonyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid; 3-(4-Methylpiperazine-1-carbonyl)-7-oxabicyclo(2.2.1)heptane-2-carboxylic acid; RefChem:911017; 1026680-07-8; ...; 2061038-65-9;
|
| 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 (In Vitro) |
Soluble in DMSO
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7270 mL | 18.6352 mL | 37.2703 mL | |
| 5 mM | 0.7454 mL | 3.7270 mL | 7.4541 mL | |
| 10 mM | 0.3727 mL | 1.8635 mL | 3.7270 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06012734 | Not yet recruiting | Drug: LB-100 Drug: Atezolizumab |
Metastatic Microsatellite- stable Colorectal Cancer |
The Netherlands Cancer Institute |
December 2023 | Phase 1 |
| NCT03886662 | Unknown | Drug: LB-100 | Myelodysplastic Syndromes | Lixte Biotechnology Holdings, Inc. |
April 2019 | Phase 1 Phase 2 |
| NCT05809830 | Recruiting | Drug: LB-100 plus Doxorrubicin Drug: Doxorubicin |
Advanced Soft-tissue Sarcoma | Grupo Espanol de Investigacion en Sarcomas |
May 29, 2023 | Phase 1 Phase 2 |
| NCT06065462 | Recruiting | Drug: Dostarlimab Drug: LB-100 |
Ovarian Clear Cell Carcinoma |
M.D. Anderson Cancer Center |
November 10, 2023 | Phase 1 Phase 2 |
| NCT04560972 | Recruiting | Drug: Atezolizumab Drug: Carboplatin |
Extensive Stage Lung Small Cell Carcinoma |
City of Hope Medical Center |
May 28, 2021 | Phase 1 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
