고마바이오텍(주)

로그인이 필요합니다.

Category 전체보기
전기영동 > 단백질 전기영동 전기영동 > 헥산 전기영동
Cat. No.전체보기

검색 결과가 없습니다.

Product전체보기

검색 결과가 없습니다.

Brand전체보기

검색 결과가 없습니다.

제품 상세

Antibody

6.5 - 270 kDa 범위를 커버하는 3가지 컬러 밴드를 포함하며,
최대 100%까지의 transfer 효과를 개런티하는 Prestained protein ladder를 소개합니다.

프린트 제품 문의

Metabolism-mediated Drug Interaction (대사 매개 의약품 상호작용의 평가)

 

간에 존재하는 Phase I (Cytochrome P450)과 Phase II (GST, UGT..) 대사효소는 대부분의 의약품 대사에 관여합니다. 의약품은 이 효소들과 작용하여 효소의 활성을 방해하거나 (CYP inhibition), nuclear receptor를 활성화시켜 gene expression을 유도합니다. (CYP induction) 

대사 매개 의약품 상호작용은 의약품이 대사 효소의 활성을 변경하여 ADME와 PK에 영향을 미칠 때 발생할 수 있습니다. 

 

1) CYP enzyme substrate assessment assays

  • 의약품이 CYP 효소에 대한 기질로 작용하는지, 즉 어떤 효소가 의약품을 대사 시키는지 평가
  • 의약품을 CYP1A12, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4등의 CYP효소와 다양한 시간에서 인큐베이션한 후, 잔량을 HPLC-MS/MS로 정량 측정
  • 의약품 소실 값을 통해 각 대사 효소에 대한 약물의 청소율 (Clearance) 확인 

CYP Enzyme Source Substrate Incubation
CYP1A2 Human recombinant CYP1A2 Test Compound 0, 15, 30, 45, 60 min, 37°C
CYP2B6 Human recombinant CYP2B6 Test Compound 0, 15, 30, 45, 60 min, 37°C
CYP2C8 Human recombinant CYP2C8 Test Compound 0, 15, 30, 45, 60 min, 37°C
CYP2C9 Human recombinant CYP2D9 Test Compound 0, 15, 30, 45, 60 min, 37°C
CYP2C19 Human recombinant CYP2C19 Test compound 0, 15, 30, 45, 60 min, 37°C
CYP2D6 Human recombinant CYP2D6 Test compound 0, 15, 30, 45, 60 min, 37°C
CYP3A4 Human recombinant CYP3A4 Test compound 0, 15, 30, 45, 60 min, 37°C


2) CYP enzyme inhibition assessment assays
  • 의약품의 CYP 효소 (CYP1A, 3A, 2B6, 2C8, 2C9, 2C19, 2D6) 활성 억제 가능성을 평가 
  • 각 CYP enzyme probe substrate의 특정한 metabolite를 정량 

a. 가역적 억제인지 평가 (10분간 37도 인큐베이션)

CYP Enzyme Substrate Measured Component Reference Inhibitor
CYP1A Phenacetin (10 µM) Acetaminophen Furafylline
CYP2B6 Bupropion (100 µM) Hydroxybupropion Clopidogrel
CYP2C8 Amodiaquine (10 µM) Desethylamodiaquine Montelukast
CYP2C9 Diclofenac (10 µM) 4'-Hydroxydiclofenac Sulfaphenazole
CYP2C19 Omeprazole (0.5 µM) 5-Hydroxyomeprazole Oxybutynin
CYP2D6 Dextromethorphan (5 µM) Dextrorphan Quinidine
CYP3A Midazolam (5 µM) 1-Hydroxymidazolam Ketoconazole
CYP3A Testosterone (50 µM) 6-Beta-hydroxytestosterone Ketoconazole

b. 시간의존적 억제 (Time-Dependant-Inhibition) 인지 평가 
(테스트 의약품을 NADPH가 생성되는 조건과 생성되지 않는 조건에서 human liver microsome과 37도에서 30분동안 사전 배양한 후 substrate를 처리하고 10분간 배양)

CYP Enzyme Substrate Measured Component Reference Inhibitor
CYP1A Phenacetin (50 µM) Acetaminophen Furafylline
CYP2B6 Bupropion (500 µM) Hydroxybupropion Thiotepa
CYP2C8 Amodiaquine (50 µM) Desethylamodiaquine Gemfibrozil Glucuronide
CYP2C9 Diclofenac (50 µM) 4'-Hydroxydiclofenac Tienilic Acid
CYP2C19 Omeprazole (10 µM) 5-Hydroxyomeprazole Iclopidine
CYP2D6 Dextromethorphan (25 µM) Dextrorphan Methylenedioxy-methamphetamine
CYP3A Midazolam (25 µM) 1-Hydroxymidazolam Troleandomycin


3) CYP enzyme induction assessment assays
  • 약물이 CYP 효소의 유도제로 작용하는지 여부 평가 
  • CYP enzymes (CYP1A2, 2B6, 3A4, 2C8, 2C9 and 2C19)의 mRNA 레벨을 qPCR로 측정하거나 probe substrate의 metabolite를 정량함으로써 효소 활성 측정

a. CYP Induction Enzyme Activity
(3 donor로부터의 냉동 hepatocyte에서 compound와 함께 72시간 배양)

CYP Enzyme Substrate Measured Component Positive Control
CYP1A Ethoxyresorufin (2 µM) Resorufin Omeprazole
CYP2B6 Bupropion (200 µM) Hydroxybupropion Phenobarbital
CYP3A Midazolam (10 µM) 1-hydroxymidazolam Rifampicin

b. CYP Induction mRNA level 
(3 donor로부터의 냉동 hepatocyte에서 compound와 함께 72시간 배양)

CYP Enzyme Measured Component Positive Control
CYP1A2 CYP1A2 mRNA Omeprazole
CYP2B6 CYP2B6 mRNA Phenobarbital
CYP3A4 CYP3A4 mRNA Rifampicin



Transporter-mediated Drug Interaction (수송체 매개 의약품 상호작용의 평가)

수송체는 독소 및 약물과 같은 내인성 및 외인성 물질을 포함하여 이온 또는 분자의 막간 이동을 촉진하는 막 단백질 입니다. 수송체는 인체 전체의 여러 기관에서 발현되며 내인성 및 외인성 물질의 접근을 제어함으로써, 약물의 약동학과 약력학에 영향을 줍니다. 약물상호작용에 관여하는 수송체 종류는 다음과 같습니다. 
  • ATP Binding cassette (ABC) transporter : P-gp, BCRP
  • Solute Carrier (SLC) transporter : OATP1B1, OATP1B3 (for hepatic clearance drugs), OAT1, OAT3, OCT2, MATE1, MATE2-K (for renal clearance drugs)


1) Transporter inhibition assay 
  • 규제 기관은 P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 및 MATE2-K에 대한 연구 약물의 억제 가능성을 테스트할 것을 권장합니다. 
  • Eurofins Discovery는 P-gp 또는 BCRP를 발현하는 HEK 세포에서 준비한 막 소포를 사용하여 P-gp 및 BCRP inhibition 분석을 제공합니다. 

Transporter Cell line / vesicles Substrate Reference inhibitor
OATP1B1 OATP1B1-CHO Estradiol 17-(β-D-glucuronide) (5 µM) Cyclosporine
OATP1B3 OATP1B3-CHO Estradiol 17-(β-D-glucuronide) (15 µM) Cyclosporine
OAT1 OAT1-CHO p-Aminohippurate (10 µM) Probenecid
OAT3 OAT3-CHO Ranitidine (10 µM) Probenecid
OCT2 OCT2-HEK Metformin (100 µM) Verapamil
MATE1 MATE1-HEK Metformin (10 µM) Verapamil
MATE2-K MATE2-K-HEK Metformin (100 µM) Verapamil
P-gp P-gp-HEK Vesicles N-methyl-quinidine (1 µM) Verapamil
BCRP BCRP-HEK Vesicles Estrone 3-sulfate (1 µM) Ko143


2) Transporter substrate assay 
  • 약물의 투과도나 용해도가 높지 않을 경우, P-gp나 BCRP의 substrate로서의 잠재성을 평가합니다.
  • 약물이 간대사나 담즙분비를 통해 제거되거나, 간으로의 약물 흡수가 임상적으로 중요하다면, OATP1B1이나 OATP1B3의 substrate로서의 잠재성을 평가합니다. 
  • 약물이 신장을 통해 주로 제거된다면 OAT1, OAT3, OCT2, MATE1이나 MATE2-K의 substrate로서의 잠재성을 평가합니다. 

Transporter Cell line Substrate Incubation and Inhibitor
P-gp Caco-2 cell line Test compound 60 min A-B and 40 min B-A, with and without Verapamil (100 µM)
BCRP Caco-2 cell line Test compound 60 min A-B and 40 min B-A, with and without Ko143 (10 µM)
OATP1B1 OATP1B1-CHO Test compound 2 min and 30 min, with and without Cyclosporine (5 µM)
OATP1B3 OATP1B3-CHO Test Compound 2 min and 30 min, with and without Cyclosporine (5 µM)
OAT1 OAT1-CHO Test Compound 2 min and 30 min with and without Probenecid (30 µM)
OAT3 OAT3-CHO Test Compound 2 min and 30 min with and without Probenecid (30 µM)
OCT2 OCT2-HEK Test Compound 2 min and 30 min, with and without Verapamil ( 50 µM)
MATE1 MATE1-HEK Test Compound 2 min and 30 min, with and without Verapamil ( 50 µM)
MATE2-K MATE2-K-HEK Test Compound 2 min and 30 min, with and without Verapamil ( 50 µM)



DDI Panel 서비스 종류

CYP450 Inhibition Assays - Human Liver Microsomes (HLM) Item # Panel
CYP Inhibition (HLM; package of 8 assays) 　 G232
CYP3A Inhibition (HLM, midazolam substrate) 1770 P
CYP3A Inhibition (HLM, testosterone substrate) 1769 P
CYP1A Inhibition (HLM, phenacetin substrate) 2064 P
CYP2B6 Inhibition (HLM, bupropion substrate) 2065 P
CYP2C8 Inhibition (HLM, amodiaquine substrate) 4481 P
CYP2C9 Inhibition (HLM, diclofenac substrate) 2066 P
CYP2C19 Inhibition (HLM, omeprazole substrate) 1772 P
CYP2D6 Inhibition (HLM, dextromethorphan substrate) 1838 P
CYP450 Inhibition Assays - Time Dependent (+/- NADPH) Item # Panel
Time-dependent CYP Inhibition (HLM; package of 14 assays) 　 G234
Time-dependent CYP3A Inhibition (HLM; midazolam substrate) G201 P
Time-dependent CYP1A Inhibition (HLM; phenacetin substrate) G197 P
Time-dependent CYP2C9 Inhibition (HLM; diclofenac substrate) G199 P
Time-dependent CYP2C19 Inhibition (HLM; omeprazole substrate) G198 P
Time-dependent CYP2D6 Inhibition (HLM; dextromethorphan substrate) G200 P
Time-dependent CYP2B6 Inhibition (HLM; bupropion substrate) G413 P
Time-dependent CYP2C8 Inhibition (HLM; amodiaquine substrate) G414 P
CYP450 Phenotyping Assays - Recombinant Item # Panel
CYP Phenotyping (recombinant, panel of 7 CYP's) 　 G230
Intrinsic clearance (CYP3A4) 1649 P
Intrinsic clearance (CYP1A2) 1645 P
Intrinsic clearance (CYP2B6) 2387 P
Intrinsic clearance (CYP2C8) 2384 P
Intrinsic clearance (CYP2C9) 1646 P
Intrinsic clearance (CYP2C19) 1647 P
Intrinsic clearance (CYP2D6) 1648 P
CYP Induction Assays - Human Hepatocytes (mRNA level) Item # Panel
CYP Induction Panel (human hepatocytes, mRNA level, 3 donors) 　 G345
CYP1A2 Induction (human hepatocytes, mRNA level, 3 donors) 3862 P
CYP2B6 Induction (human hepatocytes, mRNA level, 3 donors) 3863 P
CYP3A4 Induction (human hepatocytes, mRNA level, 3 donors) 3865 P
Drug Transporters - P-gp & BCRP Substrate Assessment Item # Panel
Caco-2 Efflux Transporter (P-gp & BCRP) Substrate Assessment Panel 　 G357
A-B Permeability (Caco-2, pH 7.4/7.4) 3319 P
B-A Permeability (Caco-2, pH 7.4/7.4) 3321 P
A-B Permeability (Caco-2, pH 7.4/7.4 + verapamil) 3325 P
B-A Permeability (Caco-2, pH 7.4/7.4 + verapamil) 3326 P
A-B Permeability (Caco-2 pH 7.4/7.4 + Ko143) 4482 P
B-A Permeability (Caco-2 pH 7.4/7.4 + Ko143) 4483 P
Drug Transporters - Liver & Renal Transporter Substrate Assessment Item # Panel
Liver Drug Transporter Substrate Assessment Panel 　 G382
OATP1B1 Substrate Assessment (OATP1B1-CHO) 5015 P
OATP1B3 Substrate Assessment (OATP1B3-CHO) 5016 P
Renal Drug Transporter Substrate Assessment Panel 　 G383
OAT1 Substrate Assessment (OAT1-CHO) 5017 P
OAT3 Substrate Assessment (OAT3-CHO) 5018 P
OCT2 Substrate Assessment (OCT2-HEK) 5094 P
MATE1 Substrate Assessment (MATE1-HEK) 5092 P
MATE2-K Substrate Assessment (MATE2-K-HEK) 5093 P
Drug Transporters - P-gp & BCRP Inhibition Item # Panel
P-gp Inhibition (P-gp-HEK Vesicles, N-methyl-quinidine Substrate) 5500 　
BCRP Inhibition (BCRP-HEK Vesicles, Estrone 3-sulfate Substrate) 5501 　
Drug Transporters - Liver & Renal Transporter Inhibition Item # Panel
Liver Drug Transporter Inhibition Panel - IC50 　 G380
OATP1B1 Inhibition IC50 (OATP1B1-CHO, Estradiol-17Beta-Glucuronide Substrate) 5038 　
OATP1B3 Inhibition IC50 (OATP1B3-CHO, Estradiol-17Beta-Glucuronide Substrate) 5040 　
Renal Drug Transporter Inhibition Panel - IC50 　 G381
OAT1 Inhibition IC50 (OAT1-CHO, P-aminohippurate Substrate) 5039 　
OAT3 Inhibition IC50 (OAT3-CHO, Ranitidine Substrate) 5041 　
OCT2 Inhibition IC50 (OCT2-HEK, Metformin Substrate) 5098 　
MATE1 Inhibition IC50 (MATE1-HEK, Metformin Substrate) 5090 　
MATE2-K Inhibition IC50 (MATE2-K-HEK, Metformin Substrate) 5096 　


주문정보

주문정보 - Cat No, PRODUCT, SIZE, 수량 등 항목으로 구성되어있습니다.
  Product Cat.No. Size Maker Qty Data Sheet
전체보기

추천제품

관련제품

주문정보 - Cat No, PRODUCT, SIZE, 수량 등 항목으로 구성되어있습니다.
  Product Cat.No. Size Maker Qty Data Sheet
전체보기

자료

웨비나/Video

TOP

제품 문의

 0.5 ml Elite Pre-stained Protein Ladder (2 x 0.25 ml) PAL-EPL-500 0.5ml 500
Maker
Cat.No.
Product
Size
Qty
Data Sheet

로그인

로그인