Print E-mail Contact us
Transporter
Transporters are transmembrane proteins that act as nature's gatekeeper for cellular entry and exit by facilitating the movement of substances including drugs across cell and organ
membranes.
Transporters can mediate drug disposition and can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. Currently there are more than 400 unique human transporters, and the body of evidence is growing rapidly for their role in DDI, ADMET and early drug discovery. More and more studies show that Inhibition or activation of a specific transporter that involves in the absorption, disposition, metabolism, elimination and toxicity (ADMET) of a drug could have significant clinical effects ranging from lowering drug efficacy to compromising safety, including drug-drug interactions (DDIs) etc. As part of the growing importance of transporters in drug development process, both FDA and EMA reviewers routinely request transporter mediated drug interaction assessment data for seven transporters including Pgp (MDR1),
BCRP, OAT1, OAT3, OATP1B1, OATP1B3, OCT2.
HD Biosciences uses proprietary knowledge and technologies to overcome the challenges associated with transporter assay development. We have successfully generated various transporter assays targeting not only FDA/EMA’s transporter safety panel but also many
drug related small panels suitable for compound profiling purpose.
FDA/SFDA Transporter Profiling Panel:
"The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule,
and information required for drug labelling."----FDA
Transporter
Gene
Cell
Model
Probe
Substrate
Reference
Inhibitor
P-gp
(MDR1)
ABCB1
MDCK-II/Caco2
[3H]-digoxin
verapamil
BCRP
ABCG2
MDCK-II/Caco-2
[3H]-estrone-3-sulfate
chrysin
OCT2
SLC22A2
MDCK-II/HEK293
[3H]-MPP+
quinidine
OAT1
SLC22A6
MDCK-II/HEK293
[3H]-p-aminohippurate
probenecid
OAT3
SLC22A8
MDCK-II/HEK293
[3H]-estrone-3-sulfate
probenecid
OATP1B1
SLCO1B1
MDCK-II/HEK293
[3H]-estrone-3-sulfate
rifampicin
OATP1B3
SLCO1B3
MDCK-II/HEK293
[3H]-estrone-3-sulfate
rifampicin
-
A full panel of seven (7) FDA transporters
-
Individual transporter expressed in polarized mammalian cells
-
Validated uptake assays
-
Inhibition screen at single or multiple concentrations
-
Designed for FDA/SFDA submissions
-
FDA/SFDA-ready report
Monoamine Transporter Screening/Profiling Panel:
Monoamine transporters (MATs) are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible for the reuptake of their associated amine neurotransmitters (serotonin, dopamine, norepinephrine). Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs, a line that can become quite blurred in many cases. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms (Adderall, Dexedrine) and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore drugs such as MDMA ("ecstasy", "molly") natural alkaloids like cocaine exert their effects
in a large part by their interaction with MATs.
Transporter
Gene
Cell
Model
Probe
Substrate
Reference
Inhibitor
SERT
SLC6A4
HEK293
[3H]Serotonin
Fluoxetine
DAT
SLC6A3
HEK293
[3H]Dopamine
Nomifensine
NET
SLC6A2
HEK293
[3H] norepinephrine
Desiparmine
-
A panel of all three transporters
-
Validated uptake/binding assays
-
Screening/profiling at single or multiple concentrations
-
FDA/SFDA-ready report
Other Transporters at HDB:
HDB carries a large collection of transporters that covers almost every major family such as cationic amino acid transpoter (ASC1, LAT2 etc), Na/K co-transporter (NKCC1), organic cation/anion/zwitterion transporter (OCT1/2, EMT, PMAT etc), Sodium-coupled neutral amino acid transporter (SNAT1/2 etc). For a full list of functional validated transporters,
please contact us at info@hdbiosciences.com.
----------------------
----------------------
HD Biosciences (China) Co.,Ltd
590 Ruiqing Road
Zhangjiang East Campus, Pudong, Shanghai 201201,
P.R.China
Tel: +86 (21) 5116 3700
Fax: +86 (21) 5116 3766
info@hdbiosciences.com
SERVICES
|
THERAPEUTIC AREAS
|
NEWS & EVENTS