| Size | Price | Stock | Qty |
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| 1mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target of LFHP-1c is phosphoglycerate mutase 5 (PGAM5), a mitochondrial protein that functions as a serine/threonine phosphatase and plays a role in mitochondrial dynamics, cell death, and oxidative stress responses. LFHP-1c is a PGAM5 inhibitor. It binds to endothelial PGAM5 to inhibit its interaction with NRF2. By inhibiting PGAM5, the compound promotes the nuclear translocation of NRF2, a key transcription factor that regulates antioxidant responses.
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| ln Vitro |
In rat brain microvascular endothelial cells (rBMECs), treatment with LFHP-1c (1, 2 or 5 μmol/L; 9 h) followed by hypoxia enhanced NRF2 protein expression and encouraged NRF2 nuclear translocation [1].
In vitro, LFHP-1c binds to PGAM5 and promotes the nuclear translocation of NRF2 in primary rat brain microvascular endothelial cells (rBMECs). This effect is observed at a concentration of 2 μmol/L after 1 hour of treatment. The compound's ability to modulate the PGAM5-NRF2 axis is central to its neuroprotective mechanism. |
| ln Vivo |
In rats, LFHP-1c (5 mg/kg; i.v.; 2 doses) inhibits disruption of the blood brain barrier after temporary middle cerebral artery occlusion (tMCAO)[1]. Through the PGAM5-NRF2 axis, LFHP-1c (3 mg/kg, 1 mL/kg; intravenous injection; 8 doses) reduces cerebral ischemia damage in the fascicularis tMCAO model[1].
In vivo, LFHP-1c demonstrates neuroprotective activity in an ischemic stroke model. In a non-human primate (cynomolgus monkey) tMCAO model, LFHP-1c (3 mg/kg, 1 mL/kg; intravenous injection) administered at 4 hours and on days 1, 2, 3, 4, 5, 6, and 7 after tMCAO onset reduces infarct volume, brain edema, and neurological deficits. These results demonstrate the compound's efficacy in a clinically relevant large animal model of stroke. |
| Enzyme Assay |
In vitro assays for LFHP-1c involve measuring its binding to PGAM5 and its effects on NRF2 nuclear translocation. Binding studies can be performed using techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The promotion of NRF2 nuclear translocation can be assessed by immunofluorescence staining or by fractionating cells and measuring NRF2 levels in the nuclear and cytosolic fractions via Western blotting.
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| Cell Assay |
Immunofluorescence[1]
Cell Types: Primary rat brain microvascular endothelial cells (rBMECs) Tested Concentrations: 2 μmol/L Incubation Duration: 1 h Experimental Results: Bound to PGAM5, to facilitate nuclear translocation of NRF2. Cellular assays for LFHP-1c are performed using primary rat brain microvascular endothelial cells (rBMECs). Cells are treated with the compound at a concentration of 2 μmol/L for 1 hour. The effects on PGAM5 binding and NRF2 nuclear translocation are assessed as described above. These assays help to elucidate the compound's mechanism of action in a cellular context. |
| Animal Protocol |
Animal/Disease Models: Nonhuman primate Macaca fascicularis model with tMCAO[1]
Doses: 3 mg/kg, 1 mL/kg Route of Administration: IV; at 4 h, 1, 2, 3, 4, 5, 6 and 7 days after tMCAO onset. Experimental Results: decreased infarct volume, brain edema and neurological deficits in Transient MCAO model in M. fascicularis. Animal/Disease Models: SD rats (230-250 g)[1] Doses: 1 mg/kg, 5 mg/kg in 0.5 mL volume Route of Administration: IV; injected at 4 or 12 h after ischemia onset, and then injected another time at 24 h post-ischemia Experimental Results: Dose-dependently protected rat brains against ischemia/reperfusion injury at 72 h after ischemia onset with a moderate therapeutic window. Prevented BBB disruption and attenuated endothelial inflammation in rat cerebral microvessels at 72 h after ischemia onset. In vivo animal studies for LFHP-1c have been conducted in a non-human primate (cynomolgus monkey) model of transient middle cerebral artery occlusion (tMCAO). The compound is administered intravenously at a dose of 3 mg/kg (1 mL/kg) at 4 hours after tMCAO onset and then daily for 7 days. Endpoints include infarct volume, brain edema, and neurological deficit scores. These studies demonstrate the compound's neuroprotective efficacy in a clinically relevant model. |
| ADME/Pharmacokinetics |
LFHP-1c has a molecular weight of 873.13 and a molecular formula of C55H64N6O4. It is soluble in DMSO at 80 mg/mL (91.62 mM). It can be formulated for in vivo studies in 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. It is typically stored at low temperature as a powder at -20°C for up to 3 years or in solution at -80°C for up to 1 year.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for LFHP-1c in the available literature. As a research chemical, it should be handled with standard safety precautions. It is not approved for human therapeutic use.
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| References | |
| Additional Infomation |
LFHP-1c is a novel PGAM5 inhibitor with neuroprotective activity in ischemic stroke models. It has a molecular formula of C55H64N6O4 and a molecular weight of 873.13. It promotes NRF2 nuclear translocation and reduces infarct volume and neurological deficits in a primate tMCAO model.
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| Molecular Formula |
C55H64N6O4
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| Molecular Weight |
873.134473800659
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| Exact Mass |
872.498
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| CAS # |
2102347-47-5
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| PubChem CID |
168355614
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| Appearance |
White to off-white solid powder
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| LogP |
11.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
65
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| Complexity |
1460
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCC(C1=CC=CC=C1C(=O)NCCCCCCCCNC(=O)C2=CC=CC=C2C3=CC=C(C=C3)CN4C5=C(C(=CC(=C5)C6=NC7=CC=CC=C7N6C)C)N=C4CCC)OC(=O)C
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| InChi Key |
OITTXMIOSJEXLY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C55H64N6O4/c1-6-8-28-50(65-39(4)62)44-23-14-16-25-46(44)55(64)57-34-20-12-10-9-11-19-33-56-54(63)45-24-15-13-22-43(45)41-31-29-40(30-32-41)37-61-49-36-42(35-38(3)52(49)59-51(61)21-7-2)53-58-47-26-17-18-27-48(47)60(53)5/h13-18,22-27,29-32,35-36,50H,6-12,19-21,28,33-34,37H2,1-5H3,(H,56,63)(H,57,64)
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| Chemical Name |
1-[2-[8-[[2-[4-[[4-methyl-6-(1-methylbenzimidazol-2-yl)-2-propylbenzimidazol-1-yl]methyl]phenyl]benzoyl]amino]octylcarbamoyl]phenyl]pentyl acetate
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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 |
| 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: 100 mg/mL (114.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (2.86 mM) in 10% DMSO 20% HS-15 70% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.86 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1453 mL | 5.7265 mL | 11.4530 mL | |
| 5 mM | 0.2291 mL | 1.1453 mL | 2.2906 mL | |
| 10 mM | 0.1145 mL | 0.5727 mL | 1.1453 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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