transporters lecture 14

Transporters: OATP

• OATP1A2

• OATP1B1

• OATP1B3

• OATP2B1

• OATP4C1

General endogenous substrates - OATP

• steroids

• Thyroxine

• Bilirubin

• Bile acids

General Drug Class - OATP

• Cholesterol drugs (statins)

• Angiotensin receptors (sartans)

• Angiotensin enzyme blockers (prils)

• Digoxin cardiac drug

Location - OATP1A2

Brain (apical)

Location - OATP1B1

Hepatocytes (Basolateral)

Location - OATP1B3

Hepatocytes (Basolateral)

Location - OATP2B1

• Hepatocytes (Basolateral)

• Small intestine

• Placenta

Location - OATP4C1

• kidney (Basolateral)

Transporters: OAT

• OAT1

• OAT2

• OAT3

• OAT4

General endogenous substrates - OAT

• uric acid

• Folic acid

• Prostaglandins

• Cyclic nucleotides (cGMP)

• Bile acids

General Drug Class - OAT

• antiviral drugs (adefovir)

• Antibiotics (cef - Cefaclor)

• Cancer drugs (methotrexate)

Location - OAT1

Kidney proximal tubule (Basolateral)

Location - OAT2

Hepatocytes (Basolateral)

Location - OAT3

Kidney

Location - OAT4

• kidney (apical)

Transporters - OCT

• OCT1

• OCT2

General endogenous substrates - OCT

• Creatinine

• Monoamine neurotransmitters

• Acetylcholine

• Bile acids

General Drug Class - OCT1

Diabetic drug (metformin)

General Drug Class - OCT2

• antiviral drug (vir - acyclovir)

• Cancer drug (cisplatin)

General Drug Class - OCT

• blood pressure drug (atenolol)

Transporters - PEPT

Just pept lol

Location - PEPT

Kidney (apical)

General endogenous substrates - PEPT

Peptides

General Drug Class - PEPT

• peptide-like drugs

• Dietary nitrogen sources

Transporters - CNT/ENT

• CNT1

• CNT2

• CNT3

• ENT

General endogenous substrates - CNT/ENT

• Gemcitabine (Cancer drug)

• Zidovudine (antiviral)

General drug class - CNT1

Pyrimidines

General Drug Class - CNT2

Purines

General Drug Class - CNT3

Pyrimidines

General drug class - ENT

Purines and Pyrimidines

Location - CNT/ENT

Brain? lol

Transporters - MATE

• MATE1

• MATE2-K

General Endogenous Substrates - MATE

• Creatinine

• Estrone Sulfate

• N-methylnicotinamide (tryptophan metabolite)

General Drug Class - MATE

• Diabetes drug (metformin)

• Cancer Drug (cisplatin)

• Blood pressure drug (atenolol)

• Ulcer drug (cimetidine)

Location - MATE1

• kidney (apical)

• Hepatocytes (apical)

Location - MATE2-K

Kidney (apical)

Transporters - MDR1

Just MDR1 lol

Location - MDR1

APICAL

• intestinal enterocytes

• Kidney

• Hepatocytes

• BBB

• placenta

General endogenous substrates - MDR1

• steroids

• Phospholipids

• Bile acids

General Drug Class - MDR1

• digoxin, verapamil (cardiac)

• Loperamide (diarrhea)

• Quinidine (arrhythmia)

• Irinotecan, Paclitaxel, Vinblastine, doxorubicin (Cancer)

• Telithromycin, Clarithromycin (antibiotics)

• Indinavir (antiviral)

• Cyclosporine (immunosuppressant)

Transporters - BCRP

Just BCRP lol

Location - BCRP

APICAL

• enterocytes

• Hepatocytes

• BBB

• Placenta

• Stem cells

General endogenous substrates - BCRP

• uric acid (urate)

• Folic acid

• Bile acids

• Dietary flavonoids

• Sulfated conjugates

General drug class - BCRP

• Daunorubicin, doxorubicin, topotecan, irinotecan, methotrexate, imatinib (cancer drug)

• Glyburide (diabetes drug)

• Nitrofurantoin (antibiotic)

• Sulfasalazine (colitis drugs)

Transporters - MRP

• MRP2

• MRP3

• MRP4

General endogenous substrates - MRP2

Conjugated Bilirubin

General endogenous substrates - MRP3

Bile acids

General endogenous substrates - MRP4

• cyclic nucleotides (cAMP, cGMP)

• Uric acid

General drug class - MRP2

• glutathione and Glucuronide conjugates of drugs

• Cancer drugs (methotrexate, etoposide)

• Antiviral drug (indinavir)

• Blood pressure drugs (valsartan, olmesartan)

General drug class - MRP3

• some glucuronide drugs

• cancer drugs (methotrexate, etoposide, vincristine)

• Glucoronide Conjugates (morphine, acetaminophen)

General drug class - MRP4

• sulfated conjugates of drugs

• Antiviral drugs (acyclovir, ritonavir, tenofovir)

• Cancer drugs (methotrexate, 6-mercaptopurine)

Location - MRP2

APICAL

• intestine

• Liver

• Kidney

Location - MRP3

BASOLATERAL

• intestine

• Liver

Location - MRP4

• Kidney (apical)

• Liver (Basolateral)

• Brain (apical)

Transporters - bile acid transporters

• ASBT

• OSTA/B

• NTCP

• BSEP

Location - ASBT

Intestines (apical)

Location - OSTA/B

• liver (Basolateral)

• Intestines (Basolateral)

Location - NTCP

Liver (Basolateral)

Location - BSEP

Liver (apical)

General endogenous substrates - ASBT, OSTA/B, NTCP, BSEP

Bile acid for all

General drug class - NTCP

Statins

General drug class - BSEP

Statins