| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Top1
Target: LMP744 targets topoisomerase I (TOP1), a nuclear enzyme that relaxes DNA supercoiling by forming transient single-strand breaks via a covalent TOP1-DNA cleavage complex (TOP1cc). LMP744 binds to and stabilizes these complexes, preventing the religation step. This trapping leads to persistent DNA damage, replication fork collapse, and apoptosis in cancer cells. The indenoisoquinoline scaffold was rationally designed to produce more stable ternary complexes and overcome drug efflux-mediated resistance. |
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| ln Vitro |
LMP744 (MJ-III-65) has a GI50 value of 0.1 μM for NCI60 cells[2].
LMP744 (0.1–5 μM, 3 days) causes a dose-dependent accumulation of cells in the S and G2 phases of the cell cycle[2]. In Vitro Activity: LMP744 shows potent TOP1 inhibition and cytotoxicity against various cancer cell lines, including those resistant to camptothecins. It forms persistent TOP1 cleavage complexes, inducing DNA damage and apoptosis. In Ewing sarcoma preclinical models, LMP744 was evaluated alongside LMP400 and LMP776. The compound overcomes multidrug resistance (MDR) and exhibits activity in NCI60 panel with GI50 values in nanomolar range. It induces S and G2 phase cell cycle arrest and protein-linked DNA breaks at nanomolar concentrations. |
| ln Vivo |
LMP744 (MJ-III65) (10-50 mg/kg) moderately active against human A253 and FaDu tumor xenografts without significant toxicity when given intraperitoneally (i.v.) once a week for four weeks in nude mice[1].
In Vivo Activity: In a Phase 1 trial (NCT03030417), 35 patients with advanced refractory solid tumors or lymphomas received LMP744 IV daily for 5 days (QDx5) in 28-day cycles. One confirmed partial response (cPR) was observed (3% ORR). In murine xenografts, LMP744 (10-50 mg/kg/week IP) showed moderate activity against A253 and FaDu head and neck tumors without significant toxicity. Canine lymphoma studies also demonstrated antitumor activity. Further clinical development may be ongoing. |
| Enzyme Assay |
In Vitro Enzyme/Receptor Binding Protocol: TOP1 activity assays measure stabilization of cleavable complexes. Typically, recombinant human TOP1 is incubated with a radiolabeled DNA substrate (e.g., 3'-end-labeled oligonucleotide) and varying compound concentrations. The reaction is stopped with SDS and proteinase K, and DNA fragments are resolved by gel electrophoresis to quantify cleaved DNA. Alternatively, plasmid relaxation assays measure inhibition of TOP1-mediated supercoil relaxation. IC50 values are determined from densitometric analysis.
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| Cell Assay |
Cell Line: P388 and P388 Top1-deficient murine leukemia cells
Concentration: 0.1-100 μM Incubation Time: 3 days Result: Induced dose-dependent accumulation of cells in the S and G2 phases of the cell cycle. In Vitro Cell-Based Assay Protocol: P388 murine leukemia cells (and P388/CPT45 TOP1-deficient) are treated with LMP744 at 0.1-100 μM for 3 days. Cell cycle distribution is analyzed by flow cytometry after propidium iodide staining. Protein-linked DNA breaks are detected by alkaline elution or comet assay. Cytotoxicity is assessed by MTT or clonogenic assays. Apoptosis is measured by Annexin V/PI and caspase activation. For resistant cell lines, MDR reversal is evaluated by comparing IC50 values with and without verapamil. |
| Animal Protocol |
Athymic nude mice (nu/nu, female, 20-25 g, 8-12 weeks old) transplanted with A253 and FaDu human head and neck xenografts[1].
10, 25, or 50 mg/kg/week, 4 weeks I.V. push via tail vein In Vivo Animal Assay Protocol: Athymic nude mice (nu/nu, female, 20-25 g, 8-12 weeks) are implanted subcutaneously with A253 or FaDu human tumor xenografts. LMP744 is administered intraperitoneally at 10, 25, or 50 mg/kg once weekly for four weeks. Tumor volumes are measured by calipers twice weekly. Body weight and general health are monitored for toxicity. At study end, tumors are excised for histology and pharmacodynamic markers. Comparison with vehicle control and reference agents is performed. |
| ADME/Pharmacokinetics |
Pharmacokinetics: Detailed PK of LMP744 is not fully published in open literature. As a small indenoisoquinoline (MW 452.46), it is expected to have moderate oral bioavailability but is typically administered IV in clinical trials. In preclinical studies, IP dosing at 10-50 mg/kg achieved therapeutic exposures. Half-life, clearance, and volume of distribution have been characterized in canine and murine models but are not publicly detailed. Clinical PK from Phase 1 would include Cmax, AUC, and t1/2.
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| Toxicity/Toxicokinetics |
Toxicity: In murine and canine studies, LMP744 at therapeutic doses (up to 50 mg/kg/week) showed no significant toxicity. In the Phase 1 trial, adverse events were likely manageable (myelosuppression, GI effects) typical of TOP1 inhibitors, but detailed toxicity profile is not fully published. Preclinical toxicology would include hematology, chemistry, and histopathology. As an investigational drug, comprehensive safety data are generated during clinical development.
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| References |
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| Additional Infomation |
LMP744, a topoisomerase-1 inhibitor, is an indomethacin derivative and a topoisomerase 1 (Top1) inhibitor with potential antitumor activity. After administration, LMP744 binds to and stabilizes broken DNA-Top1 complexes, preventing DNA rejoining, inducing stable, irreversible DNA strand breaks, inhibiting DNA repair, and ultimately leading to cell cycle arrest and apoptosis. Because tumor cells proliferate at a much higher rate than normal cells, LMP744 can specifically target cancer cells. Top1 is a DNA-modifying enzyme crucial for transcription, replication, and the repair of double-strand DNA breaks, and is overexpressed in tumor cells.
Additional Information: LMP744 has CAS 308246-52-8, molecular formula C24H24N2O7, MW 452.46. Also known as MJ-III-65 and NSC-706744. It is an indenoisoquinoline TOP1 inhibitor designed to overcome camptothecin resistance. It forms more persistent cleavage complexes and is not a substrate for ABC transporters. It has been investigated in Ewing sarcoma and other solid tumors. Phase 1 trial showed modest single-agent activity; combination strategies may be explored. Not FDA-approved, for research and clinical investigation only. |
| Molecular Formula |
C24H24N2O7
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|---|---|
| Molecular Weight |
452.45656
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| Exact Mass |
452.158
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| Elemental Analysis |
C, 63.71; H, 5.35; N, 6.19; O, 24.75
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| CAS # |
308246-52-8
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| Related CAS # |
LMP744 hydrochloride;308246-57-3
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| PubChem CID |
397888
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| Appearance |
Brown to dark brown solid powder
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| LogP |
2.321
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
802
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OCCNCCCN1C2=C(C(C3=CC(OCO4)=C4C=C23)=O)C5=CC(OC)=C(OC)C=C5C1=O
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| InChi Key |
QCSDJDQOJBQTDV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24N2O7/c1-30-17-8-13-16(11-18(17)31-2)24(29)26(6-3-4-25-5-7-27)22-14-9-19-20(33-12-32-19)10-15(14)23(28)21(13)22/h8-11,25,27H,3-7,12H2,1-2H3
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| Chemical Name |
20-[3-(2-hydroxyethylamino)propyl]-15,16-dimethoxy-5,7-dioxa-20-azapentacyclo[10.8.0.02,10.04,8.013,18]icosa-1(12),2,4(8),9,13,15,17-heptaene-11,19-dione
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| Synonyms |
LMP744; LMP-744; LMP 744; Mj-III-65; MJ-III65; MJ-III 65; NSC 706744; NSC-706744; NSC-706744
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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: ≥ 4.17 mg/mL (~9.2 mM）
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| 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 | 2.2101 mL | 11.0507 mL | 22.1014 mL | |
| 5 mM | 0.4420 mL | 2.2101 mL | 4.4203 mL | |
| 10 mM | 0.2210 mL | 1.1051 mL | 2.2101 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 |
| NCT03030417 | Completed | Drug: LMP744 | Solid Tumors Lymphoma |
National Cancer Institute (NCI) |
February 27, 2017 | Phase 1 |
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