Online Purchasing Account You are logged on as Guest. LoginRegister a New AccountShopping cart (Empty)
United States 

The Best Defense Against Multidrug Resistance

Several reasons can explain the failure of anticancer drugs to kill cancer cells. Chemotherapeutic compounds are given systemically and are therefore subject to variations in absorption, metabolism and delivery to target tissues that can be patient-specific. Tumors can be located in parts of the body drugs do not easily penetrate and could be protected by environmental conditions in their vicinity such as increased tissue hydrostatic pressure and altered tumor vasculature. Similarly to the study of antibiotic resistance in microorganisms, research on drug resistance in cancer has focused on the specific nature and genetic background of the cancer cell itself and on the genetic changes observed upon treatment with cytotoxic drugs. Until recently, the primary method for discovering mechanisms of multidrug resistance (MDR) was to positively select cancer cells surviving the presence of cytotoxic drugs and use cellular and molecular biology techniques to identify the altered expression of genes capable of conferring drug resistance on naïve cancer cells. Such studies determined that the most commonly encountered mechanism of MDR is the increased efflux of a broad class of hydrophobic cytotoxic drugs mediated by a family of energy-dependent transporters known as ATP-binding cassette (ABC) transporters.


Since their first description in the 1970s, several members of the ABC transporter family have been linked with MDR such as P-glycoprotein (Pgp, also referred to as ABCB1 or MDR1), MRP1-5 and BCRP. The lack of substrate specificity and the abundance of ABC transporter proteins (48 known ABC transporters in humans) might account for the difficulties encountered over the last 30 years in attempting to circumvent ABC-mediated MDR in vivo. Cancer specialists have worked to develop drugs that either evade efflux or inhibit the function of efflux transporters, and although progress in this area has been slow, the rationale for this approach is still strong. Taking the example of acute myeloid leukemia (AML), it still remains a challenging hematological malignancy with an estimated 14,000 new cases and 10,000 per year in the United States alone. The prognostic is particularly poor in older individuals because of a lower tolerance for the intensive chemotherapy regimen required to achieve remission and a higher prevalence of MDR primarily mediated through ABC transporters such as P-glycoprotein. As an alternative to systemic chemotherapy, monoclonal antibodies targeting CD33, a protein over-expressed in the vast majority of patients with AML, have been the focus of several preclinical and clinical investigations. Although unconjugated anti-CD33 antibodies were found to be largely ineffective in AML patients, encouraging results were obtained with gemtuzumab ozogamicin (GO), a CD33-targeting antibody conjugated with calicheamicin as the toxic moiety and capable of delivering the drug directly to the target cells with limited side-effects.

More recently, Dr. Kung Sutherland and collaborators from Seattle Genetics and the University of Washington reported the preclinical development and characterization of a novel antibody-drug conjugate (ADC) termed SGN-CD33A and consisting of an anti-CD33 monoclonal antibody conjugated to a novel synthetic pyrrolobenzodiazepine (PBD) dimer structurally related to anthramycin and isolated from Streptomyces refuineus. Molecules in the PBD family cause cell death by cross-linking of DNA and interruption of cell division. Using Enzo’s eFluxx-ID multidrug resistance kits and cell viability tests, they showed that SGN-CD33A has robust activity in vitro against a broad panel of AML cell lines and primary patient samples regardless of their MDR status and in vivo using preclinical AML models. It was also shown to be significantly more efficient than GO. Altogether, this study demonstrated that an efficient delivery system combined with a potent drug with proven cytotoxicity could circumvent a lot of the reasons why chemotherapies are often unsuccessful in patients including MDR and offered promises for the treatment of AML as well as other forms of cancer.

Enzo Life Sciences offers a comprehensive product portfolio to understand and assess multidrug resistance including our eFluxx-ID multidrug resistance assay kits. In addition, Enzo offers antibodies, recombinant proteins and small molecules, some of which are described below:

Share this TechNote

Never miss a new TechNote!

Receive our TechNotes as soon as they are published.


Follow Us!

 
comments powered by Disqus

References:

  1. Sutherland M.S.K., et al. SGN-CD33A: a novel CD33-targeting antibody–drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood (2013) 122, 1455..

Related Products

EFLUXX-ID® Green multidrug resistance assay kit 

Simple No-wash Assay for  Simultaneous Monitoring of All 3 Major ABC Transporter Proteins – MDR, BCRP & MRP
Flow Cytometry, Fluorescence microscopy | Print as PDF
 
ENZ-51029-K100 1 Kit 538.00 USD
Do you need bulk/larger quantities?
 

EFLUXX-ID® Gold multidrug resistance assay kit 

Simple no-wash assays for simultaneous monitoring of all 3 major  ABC transporter proteins – MDR, BCRP & MRP
Flow Cytometry, Fluorescence microscopy | Print as PDF
 
ENZ-51030-K100 1 Kit 538.00 USD
Do you need bulk/larger quantities?
 

Minor vault p193 protein (human), (recombinant) (His-tag) 

Produced in E. coli. Catalytic domain of human minor vault p193 protein (aa 220-574) is fused at the C-terminus to a His-tag., ≥98% | Print as PDF
 
ALX-201-286-C010 10 µg 336.00 USD
Do you need bulk/larger quantities?
 

PGP-4008 

P-glycoprotein inhibitor
365565-02-2, ≥93% | Print as PDF
 
ALX-270-290-M002 2 mg 115.00 USD
 
ALX-270-290-M010 10 mg 372.00 USD
Do you need bulk/larger quantities?
 

Reversin 121 

P-glycoprotein inhibitor
≥98% (HPLC) | Print as PDF
 
ALX-270-305-M005 5 mg 260.00 USD
Do you need bulk/larger quantities?
 

WK-X-34 

Inhibitor of P-glycoprotein and BCRP
908859-10-9 | Print as PDF
 
ALX-270-510-M001 1 mg 206.00 USD
Do you need bulk/larger quantities?
 

KS-176 

BCRP inhibitor
≥98% (TLC) | Print as PDF
 
ALX-270-512-M002 2 mg 300.00 USD
Do you need bulk/larger quantities?
 

(S)-(+)-Camptothecin 

Potent antitumor agent
7689-03-4, Isolated from Mappia foetida Miers (Nothapodytes foetida (Wt.) Sleumer)., ≥98% (HPLC) | Print as PDF
 
ALX-350-015-M050 50 mg 53.00 USD
 
ALX-350-015-M250 250 mg 182.00 USD
 
ALX-350-015-G001 1 g 397.00 USD
Do you need bulk/larger quantities?
 

Fumitremorgin C 

BCRP inhibitor
118974-02-0, Isolated from Aspergillus fumigatus., ≥96% (HPLC) | Print as PDF
 
ALX-350-127-C250 250 µg 420.00 USD
Do you need bulk/larger quantities?
 

Tryprostatin A 

Cell cycle blocker and BCRP inhibitor
171864-80-5, Isolated from Aspergillus fumigatus., ≥90% (HPLC) | Print as PDF
 
ALX-380-090-C500 500 µg 199.00 USD
Do you need bulk/larger quantities?
 

Probenecid 

MRP inhibitor
57-66-9, ≥98% (Titration NaOH 0.1M) | Print as PDF
 
ALX-430-113-G005 5 g 35.00 USD
Do you need bulk/larger quantities?
 

P-glycoprotein monoclonal antibody (C219) 

ICC, IHC (FS), IHC (PS), IP | Print as PDF
 
ALX-801-002-C100 1 ml 735.00 USD
Do you need bulk/larger quantities?
 

P-glycoprotein (human) monoclonal antibody (C494) 

Flow Cytometry, ICC, IHC (FS), IHC (PS), IP, WB | Print as PDF
 
ALX-801-003-C100 1 ml 1,004.00 USD
Do you need bulk/larger quantities?
 

P-glycoprotein (human) monoclonal antibody (JSB-1) 

Flow Cytometry, ICC, IHC (FS), IHC (PS) | Print as PDF
 
ALX-801-004-C125 125 µg 453.00 USD
 
ALX-801-004-C250 250 µg 777.00 USD
Do you need bulk/larger quantities?
 

MVP/LRP (human) monoclonal antibody (LMR5) 

Flow Cytometry, ICC, IHC (FS), IHC (PS) | Print as PDF
 
ALX-801-014-C025 25 µg 270.00 USD
 
ALX-801-014-C050 50 µg 450.00 USD
Do you need bulk/larger quantities?
 

MRP1 monoclonal antibody (MRPr1) 

Flow Cytometry, ICC, IHC (FS), IHC (PS), WB | Print as PDF
 
ALX-801-007-C125 125 µg 453.00 USD
 
ALX-801-007-C250 250 µg 830.00 USD
Do you need bulk/larger quantities?
 

P-glycoprotein (human) monoclonal antibody (MRK16) 

Flow Cytometry, IHC (FS), IP, FUNC | Print as PDF
 
ALX-801-008-C150 150 µg 1,057.00 USD
Do you need bulk/larger quantities?
 

MRP1 (human) monoclonal antibody (MRPm5) 

Flow Cytometry, ICC, IHC (FS), WB | Print as PDF
 
ALX-801-012-C250 250 µg 777.00 USD
Do you need bulk/larger quantities?
 

MRP2 (human) monoclonal antibody (M2I-4) 

ICC, IHC (FS), WB | Print as PDF
 
ALX-801-015-C250 250 µg 788.00 USD
Do you need bulk/larger quantities?
 

MRP2 monoclonal antibody (M2III-6) 

ICC, IHC (FS), IHC (PS), WB | Print as PDF
 
ALX-801-016-C250 250 µg 830.00 USD
Do you need bulk/larger quantities?
 

MRP3 (human) monoclonal antibody (M3II-9) 

Flow Cytometry, ICC, IHC (FS), WB | Print as PDF
 
ALX-801-019-C250 250 µg 820.00 USD
Do you need bulk/larger quantities?
 

MRP5 (human) monoclonal antibody (M5I-1) 

Flow Cytometry, ICC, IHC (FS), WB | Print as PDF
 
ALX-801-021-C250 250 µg 735.00 USD
Do you need bulk/larger quantities?
 

Minor vault p193 protein (human) monoclonal antibody (p193-10) 

IHC (FS), WB | Print as PDF
 
ALX-801-025-C250 250 µg 470.00 USD
Do you need bulk/larger quantities?
 

MDR3 P-glycoprotein (human) monoclonal antibody (P3II-26) 

ICC, IHC (FS), WB | Print as PDF
 
ALX-801-028-C125 125 µg 453.00 USD
 
ALX-801-028-C250 250 µg 777.00 USD
Do you need bulk/larger quantities?
 

Breast cancer resistance protein (human) monoclonal antibody (BXP-21) 

ICC, IHC (FS), IHC (PS), WB | Print as PDF
 
ALX-801-029-C125 125 µg 453.00 USD
 
ALX-801-029-C250 250 µg 788.00 USD
Do you need bulk/larger quantities?
 

Breast cancer resistance protein monoclonal antibody (BXP-53) 

ICC, IHC (FS), IHC (PS), WB | Print as PDF
 
ALX-801-036-C050 50 µg 326.00 USD
 
ALX-801-036-C100 100 µg 571.00 USD
Do you need bulk/larger quantities?
 

MRP4 monoclonal antibody (M4I-10) 

ICC, IHC (FS), WB | Print as PDF
 
ALX-801-038-C075 75 µg 430.00 USD
 
ALX-801-038-C150 150 µg 777.00 USD
Do you need bulk/larger quantities?
 

Ko143 

BCRP inhibitor
461054-93-3, ≥96% (HPLC) | Print as PDF
 
BML-EI396-0005 5 mg 135.00 USD
 
BML-EI396-0025 25 mg 522.00 USD
Do you need bulk/larger quantities?
 

S-Farnesyl-L-cysteine methyl ester 

Multidrug resistance transporter activator
125741-64-2 , Synthetic., ≥98% (TLC) | Print as PDF
 
BML-G201-0005 5 mg 87.00 USD
 
BML-G201-0025 25 mg 349.00 USD
Do you need bulk/larger quantities?
 

Recommend this page

 
For Research Use Only. Not for use in diagnostic procedures.
Keep in touch

©2017 Enzo Life Sciences, Inc.,