RO4929097 Property

Boiling point:

696.3±55.0 °C(Predicted)

Density 

1.40

storage temp. 

Store at -20°C

solubility 

≥23.47 mg/mL in DMSO; insoluble in H2O; ≥45.2 mg/mL in EtOH with ultrasonic

form 

solid

pka

12.35±0.46(Predicted)

Safety

HS Code 

29242990

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..…

RO4929097 Chemical Properties,Usage,Production

Uses

Ro 4929097 acts as a γ-secretase inhibitor used in the treatment of those suffering from solid tumors. It is used to treat pancreatic adenocarcinoma.

Definition

ChEBI: A member of the class of dibenzoazepines that is the amide formed from formal condensation of the carboxy group of 2,2-dimethyl-3-oxo-3-[(2,2,3,3,3-pentafluoropropyl)amino]propanoic acid with the amino group of (7S)-7-amino-5,7-dihydrodibe zo[b,d]azepin-6-one.

Biological Activity

ro4929097 is a small-molecule inhibitor of γ secretase with ic50 of 4 nm and ec50 of 5 nm [1]. it shows no in vitro inhibitory activity on the closely related proteases. it also has greater than 100-fold selectivity with respect to 75 other proteins of various types [1]. ro4929097 binds to γ secretase and inhibits its protease activity, therefore blocking the cleavage of notch and reducing notch signaling. up-regulaton of this signaling pathway promotes tumorigenesis of multiple cancers.ro4929097 has shown potential antitumor activity both in vitro and in vivo. it impaired the growth of melanoma cell lines and tumor formation of human primary melanoma xenograft [2]. it slowed proliferation and reduces colony formation of breast cancer cell lines[1]. in addition, ro4929097 decreased tumor formation in xenograft models of colorectal, pancreatic, lung cancer and melanoma[1, 2]. ro4929097 has been tested in multiple phase i/ii

target

γ secretase

References

1. luistro l, he w, smith m et al. preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. cancer res 2009; 69: 7672-7680. 2. huynh c, poliseno l, segura mf et al. the novel gamma secretase inhibitor ro4929097 reduces the tumor initiating potential of melanoma. plos one 2011; 6: e25264. 3. richter s, bedard pl, chen ex et al. a phase i study of the oral gamma secretase inhibitor r04929097 in combination with gemcitabine in patients with advanced solid tumors (phl-078/ctep 8575). invest new drugs 2014; 32: 243-249. 4. sahebjam s, bedard pl, castonguay v et al. a phase i study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (pjc-004/nci 8503). br j cancer 2013; 109: 943-949. 5. diaz-padilla i, hirte h, oza am et al. a phase ib combination study of ro4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors. invest new drugs 2013; 31: 1182-1191. 6. tolcher aw, messersmith wa, mikulski sm et al. phase i study of ro4929097, a gamma secretase inhibitor of notch signaling, in patients with refractory metastatic or locally advanced solid tumors. j clin oncol 2012; 30: 2348-2353. 7. strosberg jr, yeatman t, weber j et al. a phase ii study of ro4929097 in metastatic colorectal cancer. eur j cancer 2012; 48: 997-1003. 8. kolb ea, gorlick r, keir st et al. initial testing (stage 1) by the pediatric preclinical testing program of ro4929097, a gamma-secretase inhibitor targeting notch signaling. pediatr blood cancer 2012; 58: 815-818.