Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C32H36BrN5O8.BrH |
Molecular Weight | 779.473 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Br.COC(=O)C1=C(C)NC2=C(OC(=O)N3CCN(C)CC3)C=C4N(C[C@@H](CBr)C4=C12)C(=O)C5=CC6=C(N5)C(OC)=C(OC)C(OC)=C6
InChI
InChIKey=YMALQNICPSISCA-GMUIIQOCSA-N
InChI=1S/C32H36BrN5O8.BrH/c1-16-23(31(40)45-6)25-24-18(14-33)15-38(20(24)13-21(27(25)34-16)46-32(41)37-9-7-36(2)8-10-37)30(39)19-11-17-12-22(42-3)28(43-4)29(44-5)26(17)35-19;/h11-13,18,34-35H,7-10,14-15H2,1-6H3;1H/t18-;/m1./s1
Molecular Formula | C32H36BrN5O8 |
Molecular Weight | 698.561 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | BrH |
Molecular Weight | 80.912 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Pibrozelesin (KW-2189) is a semisynthetic water-soluble derivative of the antineoplastic antibiotic duocarmycin B2. Activated by carboxyl esterase, pibrozelesin alkylates DNA by binding to adenine-thymine (A-T)-rich sequences in the minor groove of DNA, thereby inhibiting DNA replication and inducing apoptosis. KW-2189 induced DNA strand breaks in H69 cells in a concentration-dependent manner. DNA cleavage is one of the major mechanisms of KW-2189-mediated cytotoxicity. KW-2189 showed evidence of anti-tumor activity in hepatocellular carcinoma (HCC). However, because of significant and prolonged hematologic toxicity, when given as a single dose every 6 weeks, further development of this drug in HCC is not possible. Pibrozelesin had been in phase II clinical trial for the treatment of advanced malignant melanoma and advanced renal cell carcinoma. No activity in metastatic renal cell carcinoma was demonstrated and the lack of significant antitumor activity in advanced malignant melanoma treatment was shown.
Originator
Approval Year
PubMed
Title | Date | PubMed |
---|---|---|
A novel antitumor antibiotic, KW-2189 is activated by carboxyl esterase and induces DNA strand breaks in human small cell lung cancer cells. | 1994 Apr |
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Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors. | 1994 May 1 |
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Phase I study of the duocarmycin semisynthetic derivative KW-2189 given daily for five days every six weeks. | 1998 Sep |
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Novel cyclopropapyrroloindole derivative (AT-3510) bearing methoxycarbonyl and trifluoromethyl groups. | 1999 Apr 22 |
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hnRNP L enhances sensitivity of the cells to KW-2189. | 2004 Feb 20 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10857997
0.4 mg/m2 for Cycle I. Cycles were repeated every 5 to 6 weeks with escalations to 0.5 mg/m2.
Route of Administration:
Intravenous
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 06:45:10 GMT 2023
by
admin
on
Sat Dec 16 06:45:10 GMT 2023
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Record UNII |
0481JCC90T
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C2156
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