| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H22Cl2N4O2.ClH |
| Molecular Weight | 469.792 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CC(C)NC1=CC(C2=CNC(=C2)C(=O)N[C@H](CO)C3=CC(Cl)=CC=C3)=C(Cl)C=N1
InChI
InChIKey=DKGYQCPFBWFTHM-FSRHSHDFSA-N
InChI=1S/C21H22Cl2N4O2.ClH/c1-12(2)26-20-8-16(17(23)10-25-20)14-7-18(24-9-14)21(29)27-19(11-28)13-4-3-5-15(22)6-13;/h3-10,12,19,24,28H,11H2,1-2H3,(H,25,26)(H,27,29);1H/t19-;/m1./s1
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C21H22Cl2N4O2 |
| Molecular Weight | 433.331 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
BVD-523 potently and selectively inhibits ERK1 and ERK2 kinases in a reversible, ATP-competitive fashion. Consistent with its mechanism of action, BVD-523 inhibits signal transduction, cell proliferation, and cell survival, most potently in cell lines bearing mutations that activate MAPK pathway signaling. Similarly, single-agent BVD-523 inhibits tumor growth in vivo in BRAF-mutant melanoma and colorectal xenografts as well as in KRAS-mutant colorectal and pancreatic models. BioMed Valley Discoveries is developing ulixertinib, a potent and selective small molecule inhibitor of ERK 1 and 2 kinases, as an oral treatment for cancers harbouring mutations in the MAPK signaling pathway. Phase I/II development of the drug for advanced cancers including, acute myeloid leukaemia and myelodysplastic syndromes is underway in the US. A phase I trial is underway in the US for pancreatic cancer.
Originator
Approval Year
Sourcing
PubMed
Sample Use Guides
In March 2016, BioMed Valley Discoveries, in collaboration with Washington University School of Medicine, initiated a phase Ib trial to evaluate the safety and efficacy of ulixertinib 600 mg bid at the RP2D in combination with nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 in patients with newly diagnosed metastatic pancreatic cancer (15-x384; NCT02608229)
Route of Administration:
Oral
In an A375 melanoma cell line containing a b-RAFV600E mutation, Ulixertinib reduces the levels of phosphorylated ERK2 (pERK) and of the phosphorylation of the downstream kinase RSK (pRSK) with IC50 of 4.1/0.14 μM, respectively. Ulixertinib also inhibits A375 cell proliferation with IC50 of 180 nM.
