| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Lartesertib targets ATM (ataxia telangiectasia mutated), a serine/threonine protein kinase that plays a central role in the DNA damage response. ATM is activated in response to DNA double-strand breaks and phosphorylates key substrates involved in cell cycle checkpoints, DNA repair, and apoptosis. By inhibiting ATM, Lartesertib disrupts the DNA damage response, sensitizing cancer cells to DNA-damaging agents such as chemotherapy and radiation.
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| ln Vitro |
In vitro, Lartesertib inhibits ATM kinase activity with high potency and can inhibit the growth of multiple hematopoietic cell lines. As an ATP-competitive inhibitor, it binds to the ATP-binding pocket of ATM and prevents substrate phosphorylation. The compound's ability to sensitize cancer cells to DNA-damaging agents makes it a valuable tool for studying the DNA damage response and for developing cancer therapeutics.
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| ln Vivo |
In vivo, Lartesertib is orally bioavailable and has potential chemo-/radio-sensitizing and antineoplastic activities. It has potential anticancer activity for the study of lung cancer. By inhibiting ATM, the compound may enhance the efficacy of chemotherapy and radiation therapy in ATM-proficient tumors. However, specific in vivo efficacy data have not been detailed in the available literature.
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| Enzyme Assay |
For in vitro kinase assays, recombinant ATM protein is incubated with a peptide substrate and ATP in kinase assay buffer. The test compound is added at various concentrations (0.1-1000 nM). Kinase activity is measured using radioactive ATP incorporation or luminescent ADP detection assays. IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
For cell proliferation assays, cancer cell lines (such as hematopoietic cell lines or lung cancer cell lines) are seeded in 96-well plates and treated with Lartesertib at concentrations ranging from 0.01-10 µM for 72 hours. Cell viability is assessed using CellTiter-Glo or MTT assays. IC50 values are calculated from dose-response curves. Combination studies with DNA-damaging agents (such as cisplatin or ionizing radiation) can be performed to assess sensitization effects.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are implanted with tumor xenografts. When tumors reach a predetermined size, mice are randomized and treated with Lartesertib via oral gavage at doses determined from pharmacokinetic studies, alone or in combination with radiation or chemotherapy. Tumor volumes are measured twice weekly. At study endpoint, tumors are collected for analysis of ATM phosphorylation and DNA damage markers.
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| ADME/Pharmacokinetics |
Lartesertib is orally bioavailable. It is soluble in DMSO at ≥90 mg/mL. Storage is recommended at -20°C for long-term stability. Further detailed PK parameters including half-life, Cmax, AUC, and tissue distribution would be available from the primary literature. The compound is for research use only and is not intended for human or veterinary use.
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| Toxicity/Toxicokinetics |
Toxicological data for Lartesertib would be available from preclinical studies. As a clinical-stage compound, it has undergone safety evaluation. Common adverse effects associated with ATM inhibitors may include myelosuppression and gastrointestinal disturbances. As a research compound, standard safety precautions should be followed. Comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
Lartesertib is an orally bioavailable ATP-competitive ataxia-telangiectasia mutant kinase (ATM) inhibitor with potential chemosensitizing/radiotherapy-enhancing and antitumor activities. After oral administration, lartesertib targets and binds to ATM, thereby inhibiting ATM kinase activity and its mediated signaling pathways. This prevents activation of DNA damage checkpoints, interferes with DNA damage repair, induces tumor cell apoptosis, and leads to the death of ATM-overexpressing tumor cells. Furthermore, by inhibiting DNA damage repair, M4076 enhances the sensitivity of tumor cells to chemotherapy and radiotherapy and improves their antitumor activity. ATM is a serine/threonine protein kinase upregulated in various cancer cell types; it is activated after DNA damage and plays a crucial role in DNA chain repair.
Lartesertib (M4076, ATM Inhibitor-5) is a potent, orally bioavailable ATP-competitive ATM inhibitor. It has chemo-/radio-sensitizing and antineoplastic activities and can inhibit hematopoietic cell line growth. Lartesertib has potential for studying lung cancer. It is an investigational compound and is not approved for clinical use. |
| Molecular Formula |
C23H21FN6O3
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|---|---|
| Molecular Weight |
448.45
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| Exact Mass |
448.165
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| CAS # |
2495096-26-7
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| Related CAS # |
(Rac)-Lartesertib;2020089-41-0
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| PubChem CID |
122599280
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| Appearance |
White to off-white solid powder
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| LogP |
2.1
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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 |
4
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| Heavy Atom Count |
33
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| Complexity |
732
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C(N(C2=C(F)C=NC=C2OC)C2C1=CN=C1C=2C=C(C(=C1)OC)C1C(C)=NN(C=1)C)=O)C
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| InChi Key |
WNEFOSMCGCLLJU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21FN6O3/c1-12-15(11-28(2)27-12)13-6-14-17(7-19(13)32-4)26-9-18-21(14)30(23(31)29(18)3)22-16(24)8-25-10-20(22)33-5/h6-11H,1-5H3
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| Chemical Name |
8-(1,3-dimethylpyrazol-4-yl)-1-(3-fluoro-5-methoxypyridin-4-yl)-7-methoxy-3-methylimidazo[4,5-c]quinolin-2-one
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| Synonyms |
Lartesertib; M-4076 HCl; M4076 HCl; 8-(1,3-Dimethyl-1H-pyrazol-4-yl)-1-(3-fluoro-5-methoxy-4-pyridinyl)-1,3-dihydro-7-methoxy-3-methyl-2H-imidazo(4,5-C)quinolin-2-one; compound 1M [PMID: 34662544]; 2H-Imidazo(4,5-C)quinolin-2-one, 8-(1,3-dimethyl-1H-pyrazol-4-yl)-1-(3-fluoro-5-methoxy-4-pyridinyl)-1,3-dihydro-7-methoxy-3-methyl-;
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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 (~223.0 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.57 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.57 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 25.0 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: ≥ 2.5 mg/mL (5.57 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 | 2.2299 mL | 11.1495 mL | 22.2990 mL | |
| 5 mM | 0.4460 mL | 2.2299 mL | 4.4598 mL | |
| 10 mM | 0.2230 mL | 1.1150 mL | 2.2299 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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