 |
Patch Clamp hERG Safety Testing Services
hERG testing for drug candidates is a crucial element of drug development, as an estimated 25-40% of all lead compounds show some level of hERG related toxicity. As a result, regulatory agencies including FDA and EMEA require hERG/IKr pre-clinical safety data as part of any investigational new drug submission. The human cardiac delayed rectifier potassium current (IKr) is carried by a channel encoded by the human ether-a-go-go–related gene (hERG). Suppression of IKr by loss of function mutations in the hERG gene or by untoward drug block can prolong the QT interval and predispose patients to the potentially lethal arrhythmia Torsades de Pointes (TdP), is now well documented. Genscript helps our clients solve hERG safety issues at early discovery stages and during preclinical development.
In contrast to the cheaper automated hERG testing methods, manual patch clamp assays can achieve higher accuracy without any compromise, and therefore, provide the most reliable results.
GenScript’s premium technology and facilities enable the delivery of this valuable service to you at the most affordable price in market. All assays are performed using our robust hERG stable cell lines
(HEK-293).
|
|
- hERG Safety Profiling Assay
- Rapid Patch Screening Service
- Sample Screening Results
| Cell Line |
HEK-293 |
| Technology |
Manual patch clamp |
| Compound |
3 - 5 mg |
| # of Compounds |
No Limitation |
| Concentrations |
0.1-30 μM
or depending on solubility |
| Number of Concentrations |
3 - 4 |
| Measurements |
3 |
| Positive Controls |
Terfenadine, astemizole, quinidine, etc. (1 positive control) |
| Test
Conditions |
Five to ten minutes exposure;
Room temperature, or 37°C (physiological condition) |
| Deliverables |
Report includes protocol summary, plus concentration-response curve and IC50 value for each compound. |
| Turnaround time |
1 - 2 weeks |
Assays
a. Test 3 - 4 concentrations (n=3), plus positive control per study, such as terfenadine, astemizole, quinidine, etc.
b. Report includes protocol summary, plus concentration-response curve and IC50 value for each compound.
Sample Requirements
Required materials: 3 - 5 mg is sufficient for small molecules.
Study requirements: The clients should provide a study requirement in detail.
Compound requirements: Customers should provide information on the physicochemical properties of the tested compounds (molecular weight, solubility and stability).
|
Cell Line
|
HEK-293
|
Technology
|
Manual patch clamp
|
Compound
|
3 - 5 mg
|
# of Compounds
|
≥10 compounds
|
Concentrations
|
1 or 10 μM
|
Number of Concentrations
|
1 - 2
|
Measurements
|
2 - 3
|
Positive Controls
|
Terfenadine, astemizole, quinidine, etc. (1 positive control)
|
Test
Conditions
|
Five to ten minutes exposure; Room temperature
|
Deliverables
|
Report includes the channel inhibition rate for each compound.
|
Turnaround time
|
1 - 2 weeks (up to 5 compounds)
|
Assays
a. Test 1 - 2 concentrations (n=2 - 3), plus positive control per study, such as terfenadine, astemizole, quinidine, etc.
b. Report includes the channel inhibition rate for each compound.
Sample Requirements
Required materials: 3 - 5 mg is sufficient for small molecules.
Study requirements: The clients should provide a study requirement in detail.
Compound requirements: Customs provide information on the physicochemical properties of the tested compounds (molecular weight, solubility and stability).
|
|
Figure. A shows the voltage-dependent relation of hERG current. Depolarization voltages from -60 to +60 mV for 4.8 s were applied in 10 mV increments, followed by a repolarization voltage of -50 mV for 5 s, with a holding voltage of -80 mV. B shows the current-voltage curve of hERG tail current. Terfenadine induced inhibition of hERG current evoked by 20 mV conditioning pulses with a return to -50 mV is illustrated in panel C. The IC50 of 35 nM (n=3, panel D) is comparable to the publish value of 52 nM (Alexander N. et al, J of Pharm. And Exper. Ther. 316(3):1098-1106, 2006).
|
Quotation and Ordering
 To request a quotation, please download and complete the Quotation/Order Form, and send it to us by email or fax.
To order, please download and complete the Quotation/Order Form and send it to us by email or fax with a formal PO (Purchase Order) or credit card information. You can also submit PO/credit card information by phone or via our Secure Online Messaging System.
If submitting samples, please mail them together with a hard copy of the completed Quotation/Order Form to: Gene Department, GenScript, 120 Centennial Ave., Piscataway, NJ 08854, US.
For questions, or to inquire about the status of your order contact us by email, phone, fax or via our Secure Online Messaging System.
Our customer service representatives are available 24 hours a day, Monday through Friday to assist you.
|
|
Email for Quotation and Ordering: order@genscript.de |
|
Ordering by Telephone: 001-732-885-9188 (USA)
Toll Free Tel. No.: 0-800-0006-320 (Germany) 0800-369-254 (Switzerland) |
|
Fax: 001-732-210-0262 001-732-885-5878 |
|
|
|
