| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H21ClNO8P |
| Molecular Weight | 481.82 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CC[C@@H]([C@H](O)C1)C2=C(OP(O)(O)=O)C=C(O)C3=C2OC(=CC3=O)C4=C(Cl)C=CC=C4
InChI
InChIKey=YRNFLVUMZIRYKY-BLLLJJGKSA-N
InChI=1S/C21H21ClNO8P/c1-23-7-6-12(16(26)10-23)19-18(31-32(27,28)29)9-15(25)20-14(24)8-17(30-21(19)20)11-4-2-3-5-13(11)22/h2-5,8-9,12,16,25-26H,6-7,10H2,1H3,(H2,27,28,29)/t12-,16+/m0/s1
| Molecular Formula | C21H21ClNO8P |
| Molecular Weight | 481.82 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Alvocidib (also known as Flavopiridol or HMR-1275) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development for the treatment of acute myeloid leukemia, by Tolero Pharmaceuticals, Inc. As a broad spectrum CDK inhibitor, Alvocidib can inhibit cell cycle progression in either G1 or G2 and induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. Alvocidib exhibits potent cytotoxicity against a wide variety of tumor cell lines (LNCAP, HCT116, A2780, K562, PC3, and Mia PaCa-2) with IC50 values ranging from 16 nM for LNCAP to 130 nM for K562. Administration of Alvocidib at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, and active against the human A2780 ovarian carcinoma implanted sc in nude mice). Alvocidib treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. Tolero Pharmaceuticals Inc. announced that the FDA has granted orphan drug designation for Alvocidib, its cyclin-dependent kinase small molecule inhibitor, for the treatment of patients with acute myeloid leukemia.
Originator
Approval Year
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
Sourcing
PubMed
Patents
Sample Use Guides
30 mg/m2 as a 30-minute intravenous (IV) infusion followed by 30 mg/m2 as a 4-hour continuous infusion. Cycles with 4-week treatment with alvocidib followed by 2-week rest period for up to a maximum of 6 cycles
Route of Administration:
Intravenous
Skov-3 and BG-1 human ovarian cancer cells were used for activity evaluation. Cells (104/ml) were distributed into 96 well plates (“Greiner”, Frickenhausen, Germany) and allowed to adhere for 24 h. Medium was replaced by fresh medium containing vehicle or treatment reagents (Alvocidib 0.01, 0.1, 1, 10 ,100, 100 nM). After the indicated treatment period, cells were fixed by adding 10% glutamatealdehyde (“Merck”, Darmstadt, Germany) solution and stained by 0.05% crystal violet (“Sigma”) in 25% methanol. Following washing three times with double distilled water, cell bound crystal violet was dissolved in 0.1 M sodium citrate and measured at 560 nm (“ELISA Reader, Tecan”, Grödig, Austria). Experiments repeated in triplicate.
