| Stereochemistry | RACEMIC |
| Molecular Formula | C10H17NO3 |
| Molecular Weight | 199.2469 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COCC1(CO)N2CCC(CC2)C1=O
InChI
InChIKey=BGBNULCRKBVAKL-UHFFFAOYSA-N
InChI=1S/C10H17NO3/c1-14-7-10(6-12)9(13)8-2-4-11(10)5-3-8/h8,12H,2-7H2,1H3
| Molecular Formula | C10H17NO3 |
| Molecular Weight | 199.2469 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
APR-246 is a methylated form of PRIMA-1, 2-hydroxymethyl-2-methoxymethyl-aza-bicyclo[2.2.2]octan-3-one (PRIMA-1MET). APR-246, is a prodrug that is converted to the Michael acceptor methylene quinuclidinone (MQ) that binds covalently to cysteines in p53, leading to refolding and restoration of wild type p53 function. MQ also targets the cellular redox balance by inhibiting thioredoxin reductase (TrxR1) and depleting glutathione. APR-246 can rescue mutant forms of the p53 family members p63 and p73 that share high sequence homology with p53. APR-246 has demonstrated compelling pre-clinical antitumor activity in a wide variety of solid and hematological (blood) tumors, including ovarian cancer, small cell lung cancer, esophageal cancer and acute myeloid leukemia (AML), among others. Furthermore, strong synergy has been seen with both traditional anticancer agents, such as chemotherapy, as well as newer mechanism-based anticancer drugs.
A Phase I clinical study has been completed, demonstrating a favorable safety profile and both biological and clinical responses in hematological tumors with mutations in the p53 gene. A Phase Ib clinical study in combination with full dose chemotherapy (carboplatin and pegylated liposomal doxorubicin) has also been completed, demonstrating a favorable safety profile in patients with high-grade serous ovarian cancer (HGSOC). APR-246 is currently in a Phase II clinical trial in patients with HGSOC, and additional Phase Ib clinical studies of APR-246 in other cancer indications are planned.
Originator
Approval Year
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Sourcing
Sample Use Guides
APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg. Maximum-tolerated dose was defined as 60 mg/kg.
Route of Administration:
Intravenous
