Cellular Mechanism, DNA Damage & Repair I
Product Name: Adriamycin (Doxorubicin) l DNA intercalator (#C2374-5)
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Adriamycin (Doxorubicin) is an intravenous, anthracycline-based antibiotic and antineoplastic agent derived
from Streptomyces bacterium. Adriamycin enters cancer cell DNA and inhibits cell replication by arresting
protein synthesis.
In HK-2 cells, adriamycin decreases cell viability in a dose-dependent manner and induces an increase in
cells in the sub G1 and G2/M phases. It also increases secretion of TNFa, decreases expression of
phosphorylated PKA and Bcl-2, and increases phosphoryled signal transducer and activator of transcription
3, phospho-ERK,and ATF3. [1]
Due to adriamycin's route of administration and cytotoxic effects, extensive research has been conducted in
the area of assisted delivery of the chemotherapeutic (liposome [2], prodrug [3], polymer, gold-particles,
etc.)
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Details
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Chemical Formula:
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C19H18FN3O.H3PO4
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CAS No.:
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459868-92-9
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Molecular weight:
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421.36
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Purity:
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> 98%
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Appearance:
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Yellow
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Chemical name:
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8-Fluoro-2-(4-methylaminomethyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]
indol-6-one phosphate
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Solubility:
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Up to 100 mM in DMSO
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Synonyms:
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AG-014699, AG014699, AG-14699, AG14699, AG-014447, PF-01367338, PF01367338,
Rucaparib phosphate, Rucaparib
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Storage:
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For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution
at -20oC
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1. "Phase II trial of the Poly(ADP-ribose) polymerase (PARP) inhibitor AG-014699 in BRCA1 and 2 mutated
advanced ovarian and breast cancer" Cancer Research UK / Newcastle Univ. Abstract 3104
2. Thomas et al., Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol.
Cancer. Ther. 2007, 6(3), 945-956. Pubmed ID: 17363489
3. Daniel et al., Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity
against childhood neuroblastoma. Clin. Cancer Res. 2009, 15(4), 1241-1249. Pubmed ID: 19174487
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Product Name: AG-014699 (PF-01367338, Rucaparib) l PARP1/2 inhibitor (#C2401-5)
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AG-014699 (Rucaparib) is an intraveneously-administered, azepinone-indole-based inhibitor of PARP 1 and 2
(Ki = 1.4 nM) [1] AG-014699 induces selective cytotoxicity in tumor cells defective in homologous
recombination repair (HRR) through BRCA1 and 2 mutation and non-BRCA mutated HRR defects. It is a potent
chemosensitizer of temozolomide (3 to 10 fold) and topotecan (1.5 to 2.3 fold) antitumor activity in
neuroblastoma cells. [2, 3]
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Details
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Chemical Formula:
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C16H17Cl2N5O2
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CAS No.:
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902135-91-5
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Molecular weight:
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382.24
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Purity:
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> 98%
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Appearance:
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Light Yellow
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Chemical name:
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4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide
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Solubility:
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Up to 25 mM in DMSO
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Synonyms:
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AT7519, AT 7519, AT-7519
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Storage:
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For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution
at -20oC
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References
1. Santo et al., AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in
multiple myeloma via GSK-3b activation and RNA polymerase II inhibition. Oncogene, 2010, 29, 2325-2336.
Pubmed ID: 20101221
2. Squires et al., Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent
kinases, in human tumor cell lines. 2009, 8, 324-332. Pubmed ID: 19174555
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Product Name: AS-1413 (Amonafide) |DNA intercalator (#C2714-5)
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Amonafide (AS-1413) is a reversible, benzoisoquinolinedione-based DNA intercalator that produces protein-
associated DNA cleaveage and single- and double-strand cleavage by mechanisms suggesting an
interaction with topoisomerase II. [1]
Amonafide has demonstrated significant activity against P388 leukemia and L1210 cell lines as well as B16
melanoma and M5076 sarcoma cell lines. [2] In phase II studies with cytarabine, overall CR rates of 42%
were observed and produced a high complete remission rate and durable responses in patients with acute
myeloid leukemia. [3]
Amonafide is easily metabolized and is a substrate of N-acetyl transferase-2 (NAT2); the acetylation adduct
is roughly equipotent to amonafide, but has been attributed to the toxicity observed in the clinic. [4]
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Details
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Chemical Formula:
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C16H17N3O2
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CAS No.:
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69408-81-7
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Molecular weight:
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283.33
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Purity:
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> 98%
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Appearance:
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Yellow
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Chemical name:
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1H-Benz[de]isoquinoline-1,3(2H)-dione, 5-amino-2-[2-(dimethylamino)ethyl]-
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Solubility:
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Up to 100 mM in DMSO
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Synonyms:
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AS-1413, AS1413, Amonafide, Nafidimide, 5-Aminomitonafide, NSC308847
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Storage:
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For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution
at -20oC
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References
1. Andersson et al., In vitro toxicity and DNA cleaving capacity of benzisoquinolinedione (nafidimide; NSC
308847) in human leukemia. Cancer Res. 1987, 47, 1040-1044. Pubmed ID: 3026621
2. Costanza et al., Amonafide: An active agent in the treatment of previously untreated advanced breast
cancer--a cancer and leukemia group B study (CALGB 8642). Clin Cancer Res., 1995, 1, 699-704. Pubmed
ID: 9816035
3. Zhu et al., Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights. J.
Hemat. Oncol. 2010, 3, 17-26. Pubmed ID: 20416083
4. Innocenti et al., Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan. Drug
Met. Dispos. 2001, 29(4), 596-600. Pubmed ID: 9816035
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Product Name: BSI-201 (Iniparib) | PARP inhibitor (#C2201-5)
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BSI-201 (Iniparib), a iodonitrobenzamide-based cytotoxic agent, was initially considered to be a PARP
inhibitor based on its abillity to inactivate PARP by means of zinc ejection from the zinc finger of the enzyme.
[1]
Despite its ability to kill normal and neoplastic cells at high concentrations (>40 uM), further studies revealed
that BSI-201 did not selectivly kill homologous-recombination (HR)-deficient cells, sensitize cells to
topoisomerase I poisons, or inhibit PARP in situ, as seen with olaparib and veliparib. [2]
Through a battery of enzymatic, cellular, and viability assays, BSI-201 was shown to nonselectively modify
cysteine-containing proteins in tumor cells. It is also postulated that the formation of nonspecific adducts can
alter stability, activity, and localization, thus inducing apoptosis, stress, cell-cycle perturbation, or DNA
damage. [3]
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Details
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Chemical Formula:
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C7H5IN2O3
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CAS No.:
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160003-66-7
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Molecular weight:
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292.03
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Purity:
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> 98%
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Appearance:
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White
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Chemical name:
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4-iodo-3-nitrobenzamide
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Solubility:
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Up to 100 mM in DMSO
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Synonyms:
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BSI-201, BSI201, BSI 201, 160003-66-7, Iniparib
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Storage:
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For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution
at -20oC
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References
1. Mendeleyev et al., Potential chemotherapeutic activity of 4-iodo-3-nitrobenzamide. Biochem. Pharmacol.
1995, 50(5), 705-714. Pubmed ID: 7669074
2. Patel et al., Failure of Iniparib to inhibit poly(ADP-Ribose) polymerase in vitro. Clin. Cancer Res. 2012, 18,
1655-1662. Pubmed ID: 22291137
3. Liu et al., Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bonafide
PARP inhibitor. Clin. Cancer Res. 2012, 18, 510-523.
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