| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
Indimitecan targets topoisomerase I (Top1), an essential nuclear enzyme involved in DNA replication and repair. By stabilizing the Top1-DNA cleavage complex, it prevents the relegation of DNA single-strand breaks, leading to the accumulation of DNA damage and ultimately cell death. Its indenoisoquinoline core distinguishes it from the camptothecin class of Top1 inhibitors.
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| ln Vitro |
The antiproliferative potency of indomethenecan (LMP776) (0-100 μM) against several human cancer cell lines is demonstrated by its mean midpoint (MGM) of 0.079 ± 0.023 μM [1]. Because of Top1 inhibition, indomitecan exhibits effective DNA cleavage [1]. For metabolic ketoreductase, indomethoxycan can act as a substrate [1].
In vitro, Indimitecan shows potent antiproliferative activity against various human cancer cell lines. It has a mean-graph midpoint (MGM) of 0.079 ± 0.023 µM across the NCI-60 cancer cell line panel. It demonstrates broad-spectrum activity, with GI50 values of <0.01 µM against several cell lines including HOP-62, HCT-116, and DU-145. It also shows potent DNA cleavage due to Top1 inhibition. |
| ln Vivo |
In vivo, Indimitecan has demonstrated antitumor efficacy in xenograft models of human cancers. Its non-camptothecin structure may offer advantages over camptothecins, such as improved stability and reduced susceptibility to drug resistance. It can be a substrate for metabolic ketone reductases, which may influence its pharmacokinetic and metabolic profile.
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| Enzyme Assay |
Topoisomerase I inhibition is assessed using a DNA relaxation assay. Purified human topoisomerase I is incubated with supercoiled plasmid DNA in the presence of varying concentrations of Indimitecan. The extent of DNA relaxation is analyzed by agarose gel electrophoresis to determine the compound's inhibitory potency.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HOP-62, HCT-116, SF-539, UACC-62, OVCAR-3, SN12C, DU-145, MCF-7 Tested Concentrations: 0-100 μM Incubation Duration: Experimental Results: Display Growth inhibition of HOP-62, HCT-116, SF-539, UACC-62, OVCAR-3, SN12C, DU, GI50 was <0.01, <0.01, 0.04, <0.01, 0.08, <0.01, <0.01 and 0.01 μM for -145 and MCF-7 cells respectively. The mean midpoint of the graph (MGM) for growth inhibition of all human cancer cell lines successfully tested (National Cancer Institute's Developmental Therapeutics Assay ("NCI60")) was 0.079 ± 0.023 μM. Antiproliferative activity is evaluated using a panel of human cancer cell lines (e.g., the NCI-60 panel). Cells are treated with Indimitecan for 48-72 hours, and cell viability is measured using a colorimetric assay (e.g., SRB or MTT). The concentration causing 50% growth inhibition (GI50) is calculated for each cell line. |
| Animal Protocol |
Antitumor efficacy is evaluated in mice bearing human tumor xenografts. Indimitecan is administered intravenously or orally, and tumor volume is measured over time. Tumor growth inhibition (TGI) is calculated by comparing the treatment group to the control group.
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| ADME/Pharmacokinetics |
As a small molecule, Indimitecan is expected to have favorable pharmacokinetic properties. It may be administered orally or intravenously. Its clearance and half-life are consistent with other topoisomerase I inhibitors. It can be a substrate for metabolic ketone reductases, which may influence its metabolic stability and elimination.
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| Toxicity/Toxicokinetics |
Based on its mechanism of DNA damage, potential toxicities include myelosuppression (decreased blood cell counts), gastrointestinal effects (nausea, vomiting, diarrhea), and other effects associated with DNA-damaging agents. As a Top1 inhibitor, it may also cause fatigue and alopecia, which are common with this class of drugs.
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| References | |
| Additional Infomation |
Indimitecan is a research compound that has been investigated in preclinical and early clinical trials for the treatment of various cancers. Its indenoisoquinoline core represents a promising class of non-camptothecin topoisomerase I inhibitors. It was developed as part of a program to identify more stable and effective Top1 inhibitors, alongside its analogue indotecan (LMP400).
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| Molecular Formula |
C25H21N3O6
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|---|---|
| Molecular Weight |
459.450746297836
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| Exact Mass |
459.143
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| Elemental Analysis |
C, 65.07; H, 5.02; N, 9.11; O, 20.80
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| CAS # |
915360-05-3
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| PubChem CID |
11519397
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| Appearance |
Brown to black solid powder
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| LogP |
3.245
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
864
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1COC2C1=CC1=C(C=2)C(C2C3C=C(C(=CC=3C(N(CCCN3C=NC=C3)C=21)=O)OC)OC)=O
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| InChi Key |
GCILEJUNEYIABW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H21N3O6/c1-31-18-8-14-17(11-19(18)32-2)25(30)28(6-3-5-27-7-4-26-12-27)23-15-9-20-21(34-13-33-20)10-16(15)24(29)22(14)23/h4,7-12H,3,5-6,13H2,1-2H3
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| Chemical Name |
20-(3-imidazol-1-ylpropyl)-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 |
LM P776; INDIMITECAN; 915360-05-3; LMP-776; V5T7S4HP8A; NSC-725776; LMP776; Indimitecan
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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 : ~8.33 mg/mL (~18.13 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 | 2.1765 mL | 10.8826 mL | 21.7652 mL | |
| 5 mM | 0.4353 mL | 2.1765 mL | 4.3530 mL | |
| 10 mM | 0.2177 mL | 1.0883 mL | 2.1765 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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