| Stereochemistry | ABSOLUTE |
| Molecular Formula | C30H42N8O3 |
| Molecular Weight | 562.7063 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)N(C[C@H]1O[C@H]([C@H](O)[C@@H]1O)N2C=NC3=C(N)N=CN=C23)[C@@H]4C[C@H](CCC5=NC6=CC(=CC=C6N5)C(C)(C)C)C4
InChI
InChIKey=LXFOLMYKSYSZQS-LURJZOHASA-N
InChI=1S/C30H42N8O3/c1-16(2)37(13-22-25(39)26(40)29(41-22)38-15-34-24-27(31)32-14-33-28(24)38)19-10-17(11-19)6-9-23-35-20-8-7-18(30(3,4)5)12-21(20)36-23/h7-8,12,14-17,19,22,25-26,29,39-40H,6,9-11,13H2,1-5H3,(H,35,36)(H2,31,32,33)/t17-,19+,22-,25-,26-,29-/m1/s1
| Molecular Formula | C30H42N8O3 |
| Molecular Weight | 562.7063 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Pinometostat, also known as EPZ-5676, is a small molecule inhibitor of histone methyltransferase with potential antineoplastic activity. Upon intravenous administration, EPZ-5676 specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes. Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L, for the treatment of patients with MLL-r, a genetically defined acute leukemia. Epizyme is conducting a phase 1 clinical trial in pediatric patients. Epizyme is evaluating preclinical combinations of pinometostat with other anti-cancer agents in MLL-r leukemia. Pinometostat is being developed in collaboration with Celgene. Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.
Originator
Approval Year
Doses
AEs
PubMed
Patents
Sample Use Guides
28-day continuous IV infusion of each 28-day cycle
Route of Administration:
Intravenous
Pinometostat reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. Pinometostat treatment results in concentration- and time-dependent reduction of H3K79 methylation without effect on the methylation status of other histone sites, which leads to inhibition of key MLL target genes and selective, apoptotic cell killing in MLL-rearranged leukemia cells. Pinometostat inhibits proliferation of MLL-AF4 rearranged cell line MV4-11 with an IC50 of 9 nM.
