Brostallicin

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 200580

CAS#: 203258-38-2 (HCl salt)

Description: Brostallicin is a synthetic, alpha-bromoacrylic, second-generation minor groove binder (MGB), related to distamycin A, with potential antineoplastic activity. Brostallicin binds to DNA minor groove DNA, after having formed a highly reactive glutathione (GSH)-brostallicin complex in the presence of the enzyme glutathione S-transferase (GST), which is overexpressed in cancer cells; DNA replication and cell division are inhibited, resulting in tumor cell death. Compared to typical MGBs, this agent appears to bind covalently to DNA in a different manner and its activity does not depend on a functional DNA mismatch repair (MMR) mechanism. Accordingly, brostallicin may be effective against MMR-defective tumors that are refractory to various anticancer agents.


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Brostallicin, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 200580
Name: Brostallicin
CAS#: 203258-38-2 (HCl salt)
Chemical Formula: C30H36BrClN12O5
Exact Mass:
Molecular Weight: 760.04
Elemental Analysis: C, 47.41; H, 4.77; Br, 10.51; Cl, 4.66; N, 22.11; O, 10.53


Synonym: PNU166196; 4(2bromoacrylamido)N(5(5(5(2guanidinoethylcarbamoyl)1methyl 1Hpyrrol3ylcarbamoyl)1methyl1Hpyrrol3ylcarbamoyl)1methyl1H pyrrol3yl)1methyl1Hpyrrole2carboxamide

IUPAC/Chemical Name: 4-(2-bromoacrylamido)-N-(5-((5-((5-((2-guanidinoethyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide hydrochloride

InChi Key: IPKHXIAPPAKHTB-UHFFFAOYSA-N

InChi Code: InChI=1S/C30H35BrN12O5.ClH/c1-16(31)25(44)36-17-9-22(41(3)12-17)27(46)38-19-11-24(43(5)14-19)29(48)39-20-10-23(42(4)15-20)28(47)37-18-8-21(40(2)13-18)26(45)34-6-7-35-30(32)33;/h8-15H,1,6-7H2,2-5H3,(H,34,45)(H,36,44)(H,37,47)(H,38,46)(H,39,48)(H4,32,33,35);1H

SMILES Code: O=C(C1=CC(NC(C(Br)=C)=O)=CN1C)NC2=CN(C)C(C(NC3=CN(C)C(C(NC4=CN(C)C(C(NCCNC(N)=N)=O)=C4)=O)=C3)=O)=C2.[H]Cl


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Related:
203258-38-2 (Brostallicin HCl salt)
203258-60-0 (Brostallicin free base).

Brostallicin is a synthetic, alpha-bromoacrylic, second-generation minor groove binder (MGB), related to distamycin A, with potential antineoplastic activity. Brostallicin binds to DNA minor groove DNA, after having formed a highly reactive glutathione (GSH)-brostallicin complex in the presence of the enzyme glutathione S-transferase (GST), which is overexpressed in cancer cells; DNA replication and cell division are inhibited, resulting in tumor cell death. Compared to typical MGBs, this agent appears to bind covalently to DNA in a different manner and its activity does not depend on a functional DNA mismatch repair (MMR) mechanism. Accordingly, brostallicin may be effective against MMR-defective tumors that are refractory to various anticancer agents. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)
 
Current developer:   
 
 


References

1. Caponigro, F.; Lorusso, D.; Fornari, G.; Barone, C.; Merlano, M.; Airoldi, M.; Schena, M.; MacArthur, R.; Weitman, S.; Jannuzzo, M. G.; Crippa, S.; Fiorentini, F.; Petroccione, A.; Comis, S. Phase I dose-escalation study of brostallicin, a minor groove binder, in combination with cisplatin in patients with advanced solid tumors. Cancer Chemotherapy and Pharmacology (2010), 66(2), 389-394. CODEN: CCPHDZ ISSN:0344-5704. AN 2010:622626

2. Pezzola, Silvia; Antonini, Giovanni; Geroni, Cristina; Beria, Italo; Colombo, Maristella; Broggini, Massimo; Marchini, Sergio; Mongelli, Nicola; Leboffe, Loris; MacArthur, Robert; Mozzi, Alessia Francesca; Federici, Giorgio; Caccuri, Anna Maria. Correction to Role of Glutathione Transferases in the Mechanism of Brostallicin Activation. Biochemistry (2010), 49(23), 4930. CODEN: BICHAW ISSN:0006-2960. AN 2010:618736

3. Rickles, Richard; Lee, Margaret S.  -Adrenergic receptor agonists for the treatment of B-cell proliferative disorders. PCT Int. Appl. (2009), 111 pp. CODEN: PIXXD2 WO 2009151569 A2 20091217 CAN 152:67621 AN 2009:1566750

4. Pezzola, Silvia; Antonini, Giovanni; Geroni, Cristina; Beria, Italo; Colombo, Maristella; Broggini, Massimo; Mongelli, Nicola; Leboffe, Loris; MacArthur, Robert; Mozzi, Alessia Francesca; Federici, Giorgio; Caccuri, Anna Maria. Role of Glutathione Transferases in the Mechanism of Brostallicin Activation. Biochemistry (2010), 49(1), 226-235. CODEN: BICHAW ISSN:0006-2960. CAN 152:111089 AN 2009:1537627

5. Lorusso, Domenica; Mainenti, Sara; Pietragalla, Antonella; Ferrandina, Gabriella; Foco, Gilda; Masciullo, Valeria; Scambia, Giovanni. Brostallicin (PNU-166196), a new minor groove DNA binder: preclinical and clinical activity. Expert Opinion on Investigational Drugs (2009), 18(12), 1939-1946. CODEN: EOIDER ISSN:1354-3784. CAN 152:110619 AN 2009:1472481

6. Bruckheimer, Elizabeth; Kiefer, Jeff; Mousses, Spyro; Shanmugam, Kandavel; Yin, Hongwei; Weitman, Steve. Target expression-based method for assessing sensitivity to brostallicin. PCT Int. Appl. (2009), 66pp. CODEN: PIXXD2 WO 2009126970 A1 20091015 CAN 151:440645 AN 2009:1262339

7. Romagnoli, Romeo; Baraldi, Pier Giovanni; Cruz-Lopez, Olga; Preti, Delia; Bermejo, Jaime; Estevez, Francisco.  -Bromoacrylamido N-Substituted Isatin Derivatives as Potent Inducers of Apoptosis in Human Myeloid Leukemia Cells. ChemMedChem (2009), 4(10), 1668-1676. CODEN: CHEMGX ISSN:1860-7179. CAN 152:51175 AN 2009:1215039

8. Guirouilh-Barbat, Josee; Zhang, Yong-Wei; Pommier, Yves. Induction of glutathione-dependent DNA double-strand breaks by the novel anticancer drug brostallicin. Molecular Cancer Therapeutics (2009), 8(7), 1985-1994. CODEN: MCTOCF ISSN:1535-7163. CAN 151:279230 AN 2009:848543

9. Romagnoli, Romeo; Baraldi, Pier Giovanni; Cruz-Lopez, Olga; Lopez-Cara, Carlota; Preti, Delia.  -halogenoacrylic derivatives of antitumor agents. Mini-Reviews in Medicinal Chemistry (2009), 9(1), 81-94. CODEN: MMCIAE ISSN:1389-5575. CAN 151:310 AN 2009:460861

10. Rickles, Richard; Lee, Margaret S. Use of adenosine A2A receptor agonists and phosphodiesterase (PDE) inhibitors for the treatment of B-cell proliferative disorders, and combinations with other agents. PCT Int. Appl. (2009), 70 pp. CODEN: PIXXD2 WO 2009011893 A2 20090122 CAN 150:160095 AN 2009:86451