| Size | Price | Stock | Qty |
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| Targets |
Lenumlostat targets lysyl oxidase-like 2 (LOXL2), a copper-dependent amine oxidase that catalyzes the crosslinking of collagen and elastin in the extracellular matrix. LOXL2 plays a critical role in tissue fibrosis and tumor progression. The compound has IC50 values of 0.71 μM for hLOXL2 and 1.17 μM for hLOXL3, with >400-fold selectivity over LOX.
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| ln Vitro |
PAT-1251 is a lysyl oxidase-like 2 (LOXL2) inhibitor that potently inhibits LOXL2 in mice, rats, and dogs (IC50 of 0.10, 1.17 μM, respectively), and has IC50 values of 0.71 and 1.17 μM for hLOXL2 and hLOXL3, respectively. 0.12 and 0.16 μM), in that order. With an inhibition rate of less than 10% at 10 μM, PAT-1251 exhibits selectivity for LOXL2 over other important members of the amine oxidase family, including diamine oxidase (DAO), copper-dependent amine oxidase, semicarbazide-sensitive amine oxidase (SSAO), and flavin-dependent Monoamine oxidase A (MAO-A) and B (MAO-B) [1].
In vitro, Lenumlostat inhibits LOXL2 with an IC50 of 0.71 μM in human whole blood assays. It shows selectivity for LOXL2 over LOX (>400-fold) and other amine oxidases. The compound potently inhibits LOXL2 in mice, rats, and dogs with IC50 values of 0.10 μM, 0.12 μM, and 0.16 μM, respectively. |
| ln Vivo |
In vivo, Lenumlostat potently inhibits LOXL2 in mice, rats, and dogs with IC50 values of 0.10 μM, 0.12 μM, and 0.16 μM, respectively. The compound is orally bioavailable and has shown efficacy in preclinical models of fibrosis. It is being developed for the treatment of fibrotic diseases.
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| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for Lenumlostat involve LOXL2 enzyme activity assays using purified recombinant LOXL2 protein. Enzyme activity is measured by detecting hydrogen peroxide production or by using fluorescent amine oxidase substrates. IC50 values are determined for hLOXL2 and hLOXL3. Selectivity is confirmed by testing against LOX and other amine oxidases.
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| Cell Assay |
In vitro cell-based assays for Lenumlostat use human whole blood or fibroblast cultures to assess LOXL2 inhibition. Cells are treated with the compound, and LOXL2 activity is measured by assessing collagen crosslinking or by using activity-based probes. The compound's effects on extracellular matrix remodeling are evaluated.
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| Animal Protocol |
In vivo animal studies for Lenumlostat have been conducted in mouse, rat, and dog models. Fibrosis models (such as bleomycin-induced lung fibrosis or CCl4-induced liver fibrosis) are used to assess the compound's efficacy. Endpoints include tissue collagen content, LOXL2 activity, and histopathological assessment of fibrosis.
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| ADME/Pharmacokinetics |
Lenumlostat (PAT1251; GB-2064) has a molecular weight of approximately 520.5 g/mol. The compound is orally bioavailable. It is supplied as a solid powder and is soluble in DMSO. Storage: powder at -20°C for 3 years or 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Lenumlostat are not extensively detailed in the available literature. The compound has been evaluated in preclinical models for fibrosis. As a LOXL2 inhibitor that affects extracellular matrix crosslinking, potential toxicities may relate to effects on tissue integrity and wound healing.
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| References | |
| Additional Infomation |
PAT-1251 is currently undergoing clinical trial NCT04054245 (PAT-1251 for the treatment of patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis). Lenumlostat is an orally administered, small-molecule, irreversible inhibitor of lysyl oxidase homologue 2 (lysyl oxidase-like protein 2; LOXL2) with potential antifibrotic activity. After oral administration, the aminomethylpyridine moiety of lenumlostat interacts with the active site of LOXL2, forming a pseudo-irreversible inhibitory complex that inhibits the catalytic activity of LOXL2. LOXL2 is a secreted glycoprotein that catalyzes the post-translational oxidative deamination of lysine residues on target proteins (including collagen and elastin) to generate deaminated lysine (lysine ene). The condensation reaction of lysine ene with other lysine or lysine forms intermolecular and intramolecular crosslinks, affecting extracellular matrix (ECM) remodeling and potentially leading to fibrosis. LOXL2 is typically highly expressed in fibrotic tissues, and inhibiting LOXL2 may help reduce the degree of fibrosis in some chronic fibrotic diseases.
Lenumlostat (PAT1251; GB-2064) (CAS 2007885-39-2) is a potent, selective, orally available LOXL2 inhibitor with an IC50 of 0.71 μM for hLOXL2. It shows >400-fold selectivity over LOX and potently inhibits LOXL2 in mice, rats, and dogs. The compound is being developed for fibrotic diseases. No clinical trial or approved indication data are available. |
| Molecular Formula |
C18H17F4N3O3
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|---|---|
| Molecular Weight |
399.339498281479
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| Exact Mass |
399.12
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| Elemental Analysis |
C, 54.14; H, 4.29; F, 19.03; N, 10.52; O, 12.02
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| CAS # |
2007885-39-2
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| Related CAS # |
Lenumlostat hydrochloride;2098884-53-6; 2098884-52-5; 2205037-03-0 (mesylate)
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| PubChem CID |
122536283
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
551
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| Defined Atom Stereocenter Count |
2
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| SMILES |
F[C@@H]1CN(C(C2C=CC=C(C=2)OC2C=C(CN)C=C(C(F)(F)F)N=2)=O)C[C@H]1O
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| InChi Key |
ODGXXYXJORZPHE-ZIAGYGMSSA-N
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| InChi Code |
InChI=1S/C18H17F4N3O3/c19-13-8-25(9-14(13)26)17(27)11-2-1-3-12(6-11)28-16-5-10(7-23)4-15(24-16)18(20,21)22/h1-6,13-14,26H,7-9,23H2/t13-,14-/m1/s1
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| Chemical Name |
[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl]methanone
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| Synonyms |
PAT1251; PAT 1251; PAT-1251
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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 (e.g. under nitrogen), 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 : ≥ 130 mg/mL (~325.54 mM)
H2O : ≥ 100 mg/mL (~250.41 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (5.43 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 21.7 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: ≥ 2.17 mg/mL (5.43 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 21.7 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: ≥ 2.17 mg/mL (5.43 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 | 2.5041 mL | 12.5207 mL | 25.0413 mL | |
| 5 mM | 0.5008 mL | 2.5041 mL | 5.0083 mL | |
| 10 mM | 0.2504 mL | 1.2521 mL | 2.5041 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04679870
Conditions:MyelofibrosisLink: https://clinicaltrials.gov/ct2/show/NCT02852551
Conditions:HealthyProducts are for research use only; We do not sell to patients
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