Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C24H22F3N5O5.ClH |
| Molecular Weight | 553.918 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.COC1=CC2=C(C=C1OC)C(OC3=CC(NC(=O)NC4=NOC(=C4)C(C)(C)C(F)(F)F)=CC=C3)=NC=N2
InChI
InChIKey=XCZIYUDQUDWQHI-UHFFFAOYSA-N
InChI=1S/C24H22F3N5O5.ClH/c1-23(2,24(25,26)27)19-11-20(32-37-19)31-22(33)30-13-6-5-7-14(8-13)36-21-15-9-17(34-3)18(35-4)10-16(15)28-12-29-21;/h5-12H,1-4H3,(H2,30,31,32,33);1H
| Molecular Formula | C24H22F3N5O5 |
| Molecular Weight | 517.4572 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24930831 | https://www.ncbi.nlm.nih.gov/pubmed/22319199
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24930831 | https://www.ncbi.nlm.nih.gov/pubmed/22319199
CEP-32496 (RXDX 105) is an orally administered, small molecule, VEGFRsparing, RET, BRAF, EGFR tyrosine kinase inhibitor, for the treatment of solid tumours, including malignant melanoma and colorectal cancer. CEP-32496 was originally discovered by Ambit Biosciences (now Daiichi Sankyo) and Cephalon (now owned by Teva) as part of a research programme to develop orally administered kinase inhibitors. The worldwide rights to the compound were licensed to Teva by Ambit, following the acquisition of Cephalon by Teva. Teva, in March 2015, entered into an asset purchase agreement with Ignyta, pursuant to which, Ignyta has acquired worldwide rights and assets of four oncology development programmes, including CEP-32496. Following the acquisition of the compound by Ignyta, CEP 32496 has been renamed to RXDX 105. Phase I/Ib development of RXDX 105 for the treatment of advanced solid tumours is underway in the US.
CNS Activity
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E. | 2012 Feb 9 |
Patents
Sample Use Guides
CEP-32496 was evaluated for antitumor efficacy and tolerability in several BRAFV600E-driven human carcinoma xenograft mouse models, including both Colo-205 and A375. Athymic nu/nu nude mice (6-8 week old, 20−25 g) were dosed orally for 14 days with either vehicle only (22% 2-hydroxypropyl-beta-cyclodextrin) or with CEP-32496 at 10, 30, or 100 mg/kg twice daily (BID), and each dose of drug was given in a volume of 0.1 mL per 20 g of body weight. All doses were well tolerated, with no mortality or significant body weight loss (<5% relative to vehicle matched controls) observed during treatment or up to 1 week post dosing. Dosing at 10 mg/kg BID had little effect on tumor growth compared to the control group. However, increasing the dose to either 30 or 100 mg/kg BID resulted in significant efficacy.
Route of Administration:
Oral
CEP-32496 has demonstrated potent and sustained antiproliferative activity in nanomolar range against A375, Colo-679, Colo-205, SK-MEL-28, HT-144, cell lines expressing BRAFV600E. The CEP-32496 were added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h.
| Substance Class |
Chemical
Created
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| Record UNII |
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