Lartesertib (M4076) is a potent inhibitor of serine/threonine protein kinase ATM (information disclosed in patent WO2022058351A1).

Physicochemical Properties

Molecular Formula	C23H21FN6O3
Molecular Weight	448.45
CAS #	2495096-26-7
Related CAS #	(Rac)-Lartesertib;2020089-41-0
PubChem CID	122599280
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	33
Complexity	732
Defined Atom Stereocenter Count	0
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
HS Tariff Code	2934.99.9001
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)

Biological Activity

References

[1]. Pharmaceutical preparation. WO2022058351A1.

Additional Infomation

Lartesertib is an orally bioavailable ATP-competitive inhibitor of ataxia telangiectasia mutated kinase (ATM), with potential chemo-/radio-sensitizing and antineoplastic activities. Upon oral administration, lartesertib targets and binds to ATM, thereby inhibiting the kinase activity of ATM and ATM-mediated signaling. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. In addition, by preventing DNA damage repair, M4076 sensitizes tumor cells to chemo- and radiotherapy and increases their anti-tumor activity. ATM, a serine/threonine protein kinase upregulated in a variety of cancer cell types, is activated in response to DNA damage and plays a key role in DNA-strand repair.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~222.99 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.