Brostallicin - CAS 203258-60-0
Catalog number:
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
Molecular Weight:
Brostallicin, a-bromo-acrylamido tetra-pyrrole derivative, is a second-generation minor groove binder (MGB) structurally related to distamycin A with potential antineoplastic activity. Compared with that of other minor groove binders, 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.
Publictions citing BOC Sciences Products
  • >> More
White crystalline powder with a mild odor
4-[[4-[[4-[[4-(2-bromoprop-2-enoylamino)-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-N-[2-(diaminomethylideneamino)ethyl]-1-methylpyrrole-2-carboxamide; brostallicin; PNU 166196; PNU-166196; PNU166196
1.14 g/cm3
Canonical SMILES:
1.Zebularine partially reverses GST methylation in prostate cancer cells and restores sensitivity to the DNA minor groove binder brostallicin.
Sabatino MA1, Geroni C, Ganzinelli M, Ceruti R, Broggini M. Epigenetics. 2013 Jun;8(6):656-65. doi: 10.4161/epi.24916. Epub 2013 Jun 14.
Brostallicin is a DNA minor groove binder that shows enhanced antitumor activity in cells with high glutathione S-transferase (GST)/glutathione content. Prostate cancer cells present, almost invariably, methylation of the GSTP1 gene promoter and, as a consequence, low levels of GST-pi expression and activity. In these cells, brostallicin shows very little activity. We tested whether pretreatment of heavily GST-methylated prostate cancer cells with demethylating agents could enhance the activity of brostallicin. Human prostate cancer cells LNCaP and DU145 were used for these studies both in vitro and in vivo. The demethylating agent zebularine was used in combination with brostallicin. Methylation specific PCR and pyrosequencing were used to determine the level of GST methylation. Pretreatment with demethylating agents enhanced the in vitro activity of brostallicin in LNCaP cells. Zebularine, in particular, induced an enhancement of activity in vivo comparable to that obtained by transfecting the human GSTP1 gene in LNCaP cells in vitro.
2.Brostallicin (PNU-166196), a new minor groove DNA binder: preclinical and clinical activity.
Lorusso D1, Mainenti S, Pietragalla A, Ferrandina G, Foco G, Masciullo V, Scambia G. Expert Opin Investig Drugs. 2009 Dec;18(12):1939-46. doi: 10.1517/13543780903401284.
Brostallicin (PNU-166196), a-bromo-acrylamido tetra-pyrrole derivative, showed high cytotoxic potency and myelotoxicity dramatically reduced compared with other minor groove DNA-binding agents. In the presence of high intracellular glutathione concentrations, which are associated with resistance to chemotherapy, brostallicin performs a DNA minor groove attack leading to alkylation of DNA nucleophilic functions. In preclinical models, the antitumor activity of brostallicin has been tested in ovarian cancer xenografts, L1210 murine leukemia models, renal, colon and prostatic cancer cells and glutathione-S-transferase (GST) transfected human breast carcinoma cells. In clinical setting, the antitumor activity of brostallicin has been tested in ovarian cancer and in soft tissue sarcoma patients. A clear therapeutic advantage is also observed in preclinical models when brostallicin is combined with anticancer agents such as cisplatin (CDDP), doxorubicin, irinotecan and docetaxel.
3.Brostallicin versus doxorubicin as first-line chemotherapy in patients with advanced or metastatic soft tissue sarcoma: an European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group randomised phase II and pharmacogenetic study.
Gelderblom H1, Blay JY2, Seddon BM3, Leahy M4, Ray-Coquard I2, Sleijfer S5, Kerst JM6, Rutkowski P7, Bauer S8, Ouali M9, Marreaud S9, van der Straaten RJ10, Guchelaar HJ10, Weitman SD11, Hogendoorn PC12, Hohenberger P13. Eur J Cancer. 2014 Jan;50(2):388-96. doi: 10.1016/j.ejca.2013.10.002. Epub 2013 Nov 8.
AIM: Brostallicin is a DNA minor groove binder that has shown activity in patients with soft tissue sarcoma (STS) failing first-line therapy. The present study assessed the safety and efficacy of first-line brostallicin in patients with advanced or metastatic STS >60 years or not fit enough to receive combination chemotherapy. A prospective explorative pharmacogenetic analysis was undertaken in parallel.
4.Role of glutathione transferases in the mechanism of brostallicin activation.
Pezzola S1, Antonini G, Geroni C, Beria I, Colombo M, Broggini M, Marchini S, Mongelli N, Leboffe L, MacArthur R, Mozzi AF, Federici G, Caccuri AM. Biochemistry. 2010 Jan 12;49(1):226-35. doi: 10.1021/bi901689s.
Brostallicin is a novel and unique glutathione transferase-activated pro-drug with promising anticancer activity, currently in phase I and II clinical evaluation. In this work, we show that, in comparison with the parental cell line showing low GST levels, the cytotoxic activity of brostallicin is significantly enhanced in the human breast carcinoma MCF-7 cell line, transfected with either human GST-pi or GST-mu. Moreover, we describe in detail the interaction of brostallicin with GSH in the presence of GSTP1-1 and GSTM2-2, the predominant GST isoenzymes found within tumor cells. The experiments reported here indicate that brostallicin binds reversibly to both isoenzymes with K(d) values in the micromolar range (the affinity being higher for GSTM2-2). Direct evidence that both GSTP1-1 and GSTM2-2 isoenzymes catalyze the Michael addition reaction of GSH to brostallicin has been obtained both by an HPLC-MS technique and by a new fluorometric assay.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Products

CAS 794466-70-9 Vemakalant

(CAS: 794466-70-9)

Vernakalant is an drug under regulatory for the treatment for conversion of atrial fibrillation. It blocks atrial potassium channels, thereby prolonging repolar...

CAS 16200-50-3 PYR-0503

(CAS: 16200-50-3)

PYR-0503, a pyrrole compound, could be commonly used in production of sorts of important compounds like some anticancer drugs and porphyrins.

(CAS: 1398609-39-6)

Sarolaner is an antiparasitic agent. It is used as veterinary drug.

(CAS: 1252927-47-1)

GSK-1071306 is one of the metabolites of pazopanib which is a inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity as a approve...

CAS 26328-04-1 Cinepazide maleate

Cinepazide maleate
(CAS: 26328-04-1)

Cinepazide maleate is a maleate salt form of cinepazide which is a vasodilator.

CAS 172377-52-5 Estradiol 3-sulfamate

Estradiol 3-sulfamate
(CAS: 172377-52-5)

Estradiol 3-sulfamate, also known as J 995 or BLE 00084, is a potent, long-acting, and orally active steroid sulfatase inhibitor (IC50= 251 nM, and Ki= 133 nM f...

CAS 116680-01-4 Mycophenolate mofetil hydrochloride

Mycophenolate mofetil hydrochloride
(CAS: 116680-01-4)

Mycophenolate mofetil is a non-competitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase I/II with IC50 of 39 nM and 27 nM, respect...

CAS 24512-63-8 Geniposide

(CAS: 24512-63-8)

Geniposide is an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis.Geniposide is widely used in multi-component injection in the treatment...

CAS 55290-63-6 Atractylodin

(CAS: 55290-63-6)

Atractylodin is an active component of the essential oil contained in the rhizomes of Atractylodes lancea and A.

CAS 532-91-2 Coixol

(CAS: 532-91-2)

Isolated from the seed of Coix lacryma-jobi L. var. meyuan (Romen.) Stapf acts as a central muscle relaxant with an anti-convulsant effect.

CAS 83-40-9 3-Methylsalicylic acid

3-Methylsalicylic acid
(CAS: 83-40-9)

3-Methylsalicylic acid has marked fibrinolytic activity in human plasma by activating its fibrinolytic system. It is a salicylic acid derivative compound, which...

CAS 472-61-7 Astaxanthin

(CAS: 472-61-7)

Carotenoid pigment found mostly in animal organisms, but also occuring in plants; thought to be the precursor of astacin. Astaxanthin is a carotenoid pigment fo...

CAS 125-03-1 Hydrocortamate hydrochloride

Hydrocortamate hydrochloride
(CAS: 125-03-1)

This active molecular is a synthetic glucocorticoid with immunosuppressive and anti-inflammatory properties. Hydrocortamate hydrochloride is applicated for the ...

Aftobetin Hydrochloride
(CAS: 1353222-83-9)

AM-156 sodium
(CAS: 1175525-98-0)

AM-156 is a bio-active chemical and detailed information has not been published yet.

CAS 1009104-85-1 Smad3 Inhibitor

Smad3 Inhibitor
(CAS: 1009104-85-1)

Smad3 Inhibitor is a inhibitor of SMAD3, which is a receptor-regulated intracellular protein that functions downstream of TGF-β and activin receptors and mediat...

(CAS: 305822-63-3)

CP-394531 is an effective Glucocorticoid receptor agonist and probably has steroid-like anti-inflammatory properties with anti-GR and anti-obesity activity in a...

CTX-0294885 hydrochloride

CTX-0294885 hydrochloride is the hydrochloride salt of CTX-0294885 which displays high affinity toward an extensive range of kinases. The evaluation of the bind...

CAS 176957-55-4 CCT007093

(CAS: 176957-55-4)

CCT007093 is a potent PPM1D inhibitor or WIP1 inhibitor that selectively reduces viability of human tumour cell lines

CAS 176975-26-1 Izonsteride

(CAS: 176975-26-1)

Izonsteride, a benzothiazolyl derivative, has been found to be a cholestenone 5-alpha reductase inhibitor that was once studied in prostate cancer and probably ...

Chemical Structure

CAS 203258-60-0 Brostallicin

Quick Inquiry

Verification code

Featured Items