Inxight Drugs

Showing 1 - 9 of 9 results

Status:

US Approved Rx (2010)

First approved in 1996

Class (Stereo):

CHEMICAL (ABSOLUTE)

Targets:

Conditions:

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell n...

ucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug. Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor. Topotecan is used for the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy. Topotecan is sold under the trade name Hycamtin.

MELPHALAN

MORE DETAILS

Q41OR9510P

Status:

Possibly Marketed Outside US

Class (Stereo):

CHEMICAL (ABSOLUTE)

Targets:

Conditions:

Development Status

Primary Target

Highest Phase

Approval Year

Condition

Treatment Modality

CNS Activity

Originator

Substance Class

Code System

ATC Level 1

ATC Level 2

ATC Level 3

ATC Level 4

Substance Form

TOPOTECAN

7M7YKX2N15

MELPHALAN

Q41OR9510P

RALTITREXED

FCB9EGG971

TOPOTECAN HYDROCHLORIDE (1:1.25)

O0BO5T84GD

TOPOTECAN HYDROCHLORIDE

956S425ZCY

MELPHALAN FLUFENAMIDE HYDROCHLORIDE

3412470A0V

MELPHALAN FLUFENAMIDE

F70C5K4786

Melphalan hydrochloride

1VXP4V453T

RALTITREXED DISODIUM

50VZN4BPUK