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Details

Stereochemistry RACEMIC
Molecular Formula C20H34O4
Molecular Weight 338.4816
Optical Activity ( + / - )
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APHIDICOLIN, (±)-

SMILES

C[C@@]1(CO)[C@H](O)CC[C@@]2(C)[C@H]1CC[C@H]3C[C@@H]4C[C@]23CC[C@]4(O)CO

InChI

InChIKey=NOFOAYPPHIUXJR-APNQCZIXSA-N
InChI=1S/C20H34O4/c1-17(11-21)15-4-3-13-9-14-10-19(13,7-8-20(14,24)12-22)18(15,2)6-5-16(17)23/h13-16,21-24H,3-12H2,1-2H3/t13-,14+,15-,16+,17-,18-,19-,20-/m0/s1

HIDE SMILES / InChI

Molecular Formula C20H34O4
Molecular Weight 338.4816
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Aphidicolin, a tetracyclic diterpenoid obtained from the culture filtrates of Cephalosporium aphidicola and other fungi, inhibits the growth of eukaryotic cells and of certain animal viruses (SV40, Herpes and Vaccinia viruses) by selectively inhibiting the cellular replicative DNA polymerase alpha or the viral-induced DNA polymerases. The arrest of cellular or viral growth is thus due to inhibition of cellular or viral replicative DNA synthesis without interference with mitochondrial DNA synthesis, RNA, protein and nucleic acid precursors synthesis or other major metabolic pathways. The inhibition of all sensitive eukaryotic DNA polymerases by aphidicolin is competitive with respect to dCTP. Aphidicolin has thus proved extremely useful in elucidating the functional role of DNA polymerase alpha in nuclear DNA replication, of DNA polymerase gamma in mitochondrial DNA synthesis and both DNA polymerases beta and alpha in DNA repair synthesis. An important laboratory application of aphidicolin is the synchronization of the cell cycle of eukaryotic cells both in culture and in vivo. The properties of aphidicolinhave recently aroused considerable interest for its possible exploitation in al practice. The mechanism of action of this drug suggests in fact that it may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
20.0 µM [EC50]
0.59 µM [IC50]
0.4 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
s.c. M5076 mouse sarcoma model: The most effective schedule was the 7-day infusion. With the 300-mg/kg/day infusion rate,
Route of Administration: Intraperitoneal
In Vitro Use Guide
DNA synthesis was inhibited in Ehrlich ascites tumor cells using Aphidicolin at 0.02–2 ug/mL, and at 100 ug/mL in Xenopus egg extracts
Substance Class Chemical
Record UNII
6B3F8QW8TU
Record Status Validated (UNII)
Record Version