XL765 Property

Density 

1.387±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

insoluble in H2O; insoluble in EtOH; ≥15 mg/mL in DMSO

form 

solid

pka

5.88±0.30(Predicted)

color 

Light yellow to yellow

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

XL765 Chemical Properties,Usage,Production

Uses

XL765 is a low-molecular mass PI3K inhibitor that also inhibits DNA-PK and mTOR.

Definition

ChEBI: XL765 is a sulfonamide obtained by formal condensation of the sulfonic acid group of 4-[(3-methoxy-4-methylbenzoyl)amino]benzenesulfonic acid with the primary aromatic amino group of N-(3,5-dimethoxyphenyl)quinoxaline-2,3-diamine. A dual PI3K/mTOR inhibitor used in cancer treatment. It has a role as an EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor, an antineoplastic agent and a mTOR inhibitor. It is a sulfonamide, a quinoxaline derivative, an aromatic amine, a member of benzamides and an aromatic ether.

Biological Activity

sar245409 (xl765) is a selective dual inhibitor of pi3k and mtor (ic50= 9 nm for pi3kγ).pi3k (phosphatidylinositol-4,5-bisphosphate 3-kinase) is a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. it plays a key role in pi3k/akt/mtor pathway.in pa cell lines, combination of xl765 and tmz blocked the cell growth and led to apoptosis [1]. in a variety of tumor cell lines that mutated on pi3k signaling, xl765 inhibited pip3 formation in the membrane and akt/p70s6k/s6 phosphorylation [2].in gh3 xenograft tumor mouse models, combination use of xl765 and tmz inhibited tumor growth, reduced serum gh and prolactin levels with no increased systemic side effects [1]. in severe combined immunodeficient mice, xl765 abolished mpnst local and metastatic growth. [3]. in multiple human xenograft models in nude mice, repeat dose administration showed significant tumor growth inhibition that related to antiproliferative and antiangiogenic response etc. [2]

References

1. dai c, zhang b, liu x et al. inhibition of pi3k/akt/mtor pathway enhances temozolomide-induced cytotoxicity in pituitary adenoma cell lines in vitro and xenografted pituitary adenoma in female nude mice. endocrinology. 2013 mar;154(3):1247-59.2. yu p, laird ad, du x et al. characterization of the activity of the pi3k/mtor inhibitor xl765 (sar245409) in tumor models with diverse genetic alterations affecting the pi3k pathway. molcancer ther. 2014 may;13(5):1078-91.3. ghadimi mp, lopez g, torres ke et al. targeting the pi3k/mtor axis, alone and in combination with autophagy blockade, for the treatment of malignant peripheral nerve sheath tumors. mol cancer ther. 2012 aug;11(8):1758-69.