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Identification
NameSirolimus
Accession NumberDB00877  (APRD00178, DB02439)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [PubChem]

Structure
Thumb
Synonyms
(-)-Rapamycin
Rapamycin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gd-sirolimustablet5 mgoralGenmed A Division Of Pfizer Canada IncNot applicableNot applicableCanada
Gd-sirolimustablet2 mgoralGenmed A Division Of Pfizer Canada IncNot applicableNot applicableCanada
Gd-sirolimustablet1.0 mgoralGenmed A Division Of Pfizer Canada IncNot applicableNot applicableCanada
Gd-sirolimussolution1.0 mgoralGenmed A Division Of Pfizer Canada IncNot applicableNot applicableCanada
Rapamunesolution1 mg/mLoralWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.1999-09-01Not applicableUs
Rapamunetablet, sugar coated1 mg/1oralCardinal Health2001-07-01Not applicableUs
Rapamunetablet5 mgoralPfizer Canada IncNot applicableNot applicableCanada
Rapamunetablet, sugar coated2 mg/1oralWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.2001-07-01Not applicableUs
Rapamunetablet2 mgoralPfizer Canada IncNot applicableNot applicableCanada
Rapamunetablet, sugar coated1 mg/1oralWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.2001-07-01Not applicableUs
Rapamunetablet1.0 mgoralPfizer Canada Inc2003-03-25Not applicableCanada
Rapamunetablet, sugar coated.5 mg/1oralWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.2010-03-01Not applicableUs
Rapamune Oral Solutionsolution1.0 mgoralPfizer Canada Inc2001-05-15Not applicableCanada
Sirolimustablet, sugar coated2 mg/1oralGreenstone LLC2014-10-27Not applicableUs
Sirolimustablet, sugar coated1 mg/1oralGreenstone LLC2014-10-27Not applicableUs
Sirolimustablet, sugar coated.5 mg/1oralGreenstone LLC2014-01-07Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sirolimustablet1 mg/1oralDr. Reddy's Laboratories Limited2014-10-27Not applicableUs
Sirolimustablet, film coated.5 mg/1oralZydus Pharmaceuticals (USA) Inc.2014-01-15Not applicableUs
Sirolimustablet, film coated.5 mg/1oralAmerican Health Packaging2015-03-31Not applicableUs
Sirolimustablet1 mg/1oralAmerican Health Packaging2015-10-15Not applicableUs
Sirolimustablet, film coated.5 mg/1oralCadila Healthcare Limited2014-01-15Not applicableUs
Sirolimustablet2 mg/1oralDr. Reddy's Laboratories Limited2014-10-27Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIW36ZG6FT64
CAS number53123-88-9
WeightAverage: 914.1719
Monoisotopic: 913.555141619
Chemical FormulaC51H79NO13
InChI KeyInChIKey=QFJCIRLUMZQUOT-KLHQEZAJSA-N
InChI
InChI=1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33+,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1
IUPAC Name
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2S)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0⁴,⁹]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
SMILES
[H][C@@]1(C[[email protected]](C)[C@]2([H])CC(=O)[[email protected]](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[[email protected]](C)C[[email protected]](C)\C=C\C=C\C=C(C)\[[email protected]](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](O)[C@@H](C1)OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as macrolide lactams. These are cyclic polyketides containing both a cyclic amide and a cyclic ester group.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolide lactams
Sub ClassNot Available
Direct ParentMacrolide lactams
Alternative Parents
Substituents
  • Macrolide lactam
  • Macrolide
  • Alpha-amino acid ester
  • Cyclohexanol
  • Piperidine
  • Oxane
  • Tertiary carboxylic acid amide
  • Cyclic alcohol
  • Cyclic ketone
  • Tertiary amine
  • Secondary alcohol
  • Lactone
  • Lactam
  • Ketone
  • Hemiacetal
  • Carboxylic acid ester
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the prophylaxis of organ rejection in patients receiving renal transplants.
PharmacodynamicsSirolimus, a macrocyclic lactone produced by Streptomyces hygroscopicus, is an immunosuppressive agent indicated for the prophylaxis of organ rejection in patients receiving renal transplants. It is recommended that sirolimus be used in a regimen with cyclosporine and corticosteroids.
Mechanism of actionSirolimus inhibits T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin IL-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus:FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G1 to the S phase of the cell cycle.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding92%
Metabolism
SubstrateEnzymesProduct
Sirolimus
41-O-demethylrapamycinDetails
Route of eliminationNot Available
Half life57-63 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7841
Blood Brain Barrier-0.9599
Caco-2 permeable-0.6341
P-glycoprotein substrateSubstrate0.8052
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IIInhibitor0.8021
Renal organic cation transporterNon-inhibitor0.8116
CYP450 2C9 substrateNon-substrate0.878
CYP450 2D6 substrateNon-substrate0.9138
CYP450 3A4 substrateSubstrate0.7776
CYP450 1A2 substrateNon-inhibitor0.9007
CYP450 2C9 inhibitorNon-inhibitor0.9125
CYP450 2D6 inhibitorNon-inhibitor0.9414
CYP450 2C19 inhibitorNon-inhibitor0.9158
CYP450 3A4 inhibitorNon-inhibitor0.9333
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9742
Ames testNon AMES toxic0.6617
CarcinogenicityNon-carcinogens0.9546
BiodegradationNot ready biodegradable0.9593
Rat acute toxicity2.8689 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9831
hERG inhibition (predictor II)Non-inhibitor0.8443
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Wyeth pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Solutionoral1 mg/mL
Tabletoral1.0 mg
Tabletoral2 mg
Tabletoral5 mg
Tablet, sugar coatedoral.5 mg/1
Tablet, sugar coatedoral1 mg/1
Tablet, sugar coatedoral2 mg/1
Solutionoral1.0 mg
Tabletoral1 mg/1
Tabletoral2 mg/1
Tablet, film coatedoral.5 mg/1
Prices
Unit descriptionCostUnit
Rapamune 2 mg tablet20.59USD tablet
Rapamune 1 mg/ml Solution12.19USD ml
Rapamune 1 mg tablet11.95USD tablet
Rapamune 0.5 mg tablet5.86USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2103571 No2003-04-292012-02-21Canada
CA2293793 No2006-07-112018-06-11Canada
US5212155 No1993-05-182010-05-18Us
US5989591 Yes1998-09-112018-09-11Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP4.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00173 mg/mLALOGPS
logP4.85ALOGPS
logP7.45ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area195.43 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity250.66 m3·mol-1ChemAxon
Polarizability100.46 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Madhup K. Dhaon, Chi-nung Hsiao, Subhash R. Patel, Peter J. Bonk, Sanjay R. Chemburkar, Yong Y. Chen, “One pot synthesis of tetrazole derivatives of sirolimus.” U.S. Patent US20080167335, issued July 10, 2008.

US20080167335
General References
  1. Pritchard DI: Sourcing a chemical succession for cyclosporin from parasites and human pathogens. Drug Discov Today. 2005 May 15;10(10):688-91. [PubMed:15896681 ]
  2. Shuchman M: Trading restenosis for thrombosis? New questions about drug-eluting stents. N Engl J Med. 2006 Nov 9;355(19):1949-52. [PubMed:17093244 ]
  3. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, Khuri FR: Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res. 2005 Aug 15;65(16):7052-8. [PubMed:16103051 ]
  4. Chan S: Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer. Br J Cancer. 2004 Oct 18;91(8):1420-4. [PubMed:15365568 ]
  5. Graziani EI: Recent advances in the chemistry, biosynthesis and pharmacology of rapamycin analogs. Nat Prod Rep. 2009 May;26(5):602-9. doi: 10.1039/b804602f. Epub 2009 Mar 5. [PubMed:19387497 ]
External Links
ATC CodesL04AA10S01XA23
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelDownload (480 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Sirolimus.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Sirolimus.
AprepitantThe serum concentration of Sirolimus can be increased when it is combined with Aprepitant.
BenazeprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Benazepril.
BexaroteneThe serum concentration of Sirolimus can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Sirolimus can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Sirolimus can be decreased when it is combined with Bosentan.
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Sirolimus.
CaptoprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Captopril.
ChlorpropamideThe therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Sirolimus.
CilazaprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Cilazapril.
ClarithromycinThe metabolism of Sirolimus can be decreased when combined with Clarithromycin.
ClotrimazoleThe serum concentration of Sirolimus can be increased when it is combined with Clotrimazole.
ClozapineThe risk or severity of adverse effects can be increased when Sirolimus is combined with Clozapine.
ConivaptanThe serum concentration of Sirolimus can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Sirolimus can be increased when it is combined with Crizotinib.
CyclosporineThe risk or severity of adverse effects can be increased when Sirolimus is combined with Cyclosporine.
DabrafenibThe serum concentration of Sirolimus can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Sirolimus can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Sirolimus can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Sirolimus.
EfavirenzThe serum concentration of Sirolimus can be decreased when it is combined with Efavirenz.
EnalaprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Enalapril.
EnalaprilatThe risk or severity of adverse effects can be increased when Sirolimus is combined with Enalaprilat.
EnzalutamideThe serum concentration of Sirolimus can be decreased when it is combined with Enzalutamide.
ErythromycinThe metabolism of Sirolimus can be decreased when combined with Erythromycin.
FluconazoleThe metabolism of Sirolimus can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Sirolimus can be increased when it is combined with Fosaprepitant.
FosinoprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Fosinopril.
FosphenytoinThe serum concentration of Sirolimus can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Sirolimus can be increased when it is combined with Fusidic Acid.
GliclazideThe therapeutic efficacy of Gliclazide can be decreased when used in combination with Sirolimus.
GlimepirideThe therapeutic efficacy of Glimepiride can be decreased when used in combination with Sirolimus.
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Sirolimus.
GlyburideThe therapeutic efficacy of Glyburide can be decreased when used in combination with Sirolimus.
IdelalisibThe serum concentration of Sirolimus can be increased when it is combined with Idelalisib.
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Sirolimus.
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Sirolimus.
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Sirolimus.
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Sirolimus.
Insulin HumanThe therapeutic efficacy of Insulin Regular can be decreased when used in combination with Sirolimus.
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Sirolimus.
ItraconazoleThe serum concentration of Sirolimus can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Sirolimus can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Sirolimus can be increased when it is combined with Ketoconazole.
LeflunomideThe risk or severity of adverse effects can be increased when Sirolimus is combined with Leflunomide.
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Sirolimus.
LisinoprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Lisinopril.
LuliconazoleThe serum concentration of Sirolimus can be increased when it is combined with Luliconazole.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Sirolimus.
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Sirolimus.
MifepristoneThe serum concentration of Sirolimus can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Sirolimus can be decreased when it is combined with Mitotane.
MoexiprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Moexipril.
NatalizumabThe risk or severity of adverse effects can be increased when Sirolimus is combined with Natalizumab.
NelfinavirThe serum concentration of Sirolimus can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Sirolimus can be increased when it is combined with Netupitant.
PalbociclibThe serum concentration of Sirolimus can be increased when it is combined with Palbociclib.
PerindoprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Perindopril.
PhenytoinThe serum concentration of Sirolimus can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Sirolimus.
PosaconazoleThe serum concentration of Sirolimus can be increased when it is combined with Posaconazole.
QuinaprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Quinapril.
RamiprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Ramipril.
RanolazineThe serum concentration of Sirolimus can be increased when it is combined with Ranolazine.
RepaglinideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Sirolimus.
RifampicinThe metabolism of Sirolimus can be increased when combined with Rifampicin.
RitonavirThe serum concentration of Sirolimus can be increased when it is combined with Ritonavir.
RoflumilastRoflumilast may increase the immunosuppressive activities of Sirolimus.
SaquinavirThe serum concentration of Sirolimus can be increased when it is combined with Saquinavir.
SaxagliptinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Sirolimus.
SiltuximabThe serum concentration of Sirolimus can be decreased when it is combined with Siltuximab.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Sirolimus.
St. John's WortThe serum concentration of Sirolimus can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Sirolimus can be increased when it is combined with Stiripentol.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Sirolimus.
TelaprevirThe serum concentration of Sirolimus can be increased when it is combined with Telaprevir.
TelithromycinThe metabolism of Sirolimus can be decreased when combined with Telithromycin.
TesmilifeneThe serum concentration of Sirolimus can be decreased when it is combined with Tesmilifene.
TocilizumabThe serum concentration of Sirolimus can be decreased when it is combined with Tocilizumab.
TofacitinibSirolimus may increase the immunosuppressive activities of Tofacitinib.
TolbutamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Sirolimus.
TrandolaprilThe risk or severity of adverse effects can be increased when Sirolimus is combined with Trandolapril.
TrastuzumabTrastuzumab may increase the neutropenic activities of Sirolimus.
VerapamilThe serum concentration of Sirolimus can be increased when it is combined with Verapamil.
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Sirolimus.
VoriconazoleThe serum concentration of Sirolimus can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Tfiiic-class transcription factor binding
Specific Function:
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activ...
Gene Name:
MTOR
Uniprot ID:
P42345
Molecular Weight:
288889.05 Da
References
  1. Dowling RJ, Topisirovic I, Fonseca BD, Sonenberg N: Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta. 2010 Mar;1804(3):433-9. doi: 10.1016/j.bbapap.2009.12.001. Epub 2009 Dec 11. [PubMed:20005306 ]
  2. Shuuin T, Karashima H: [Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma]. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9. [PubMed:19620795 ]
  3. Sehgal SN: Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003 May;35(3 Suppl):7S-14S. [PubMed:12742462 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
other
General Function:
Type i transforming growth factor beta receptor binding
Specific Function:
Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins....
Gene Name:
FKBP1A
Uniprot ID:
P62942
Molecular Weight:
11950.665 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Sehgal SN: Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003 May;35(3 Suppl):7S-14S. [PubMed:12742462 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
other/unknown
General Function:
Ligand-dependent nuclear receptor transcription coactivator activity
Specific Function:
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name:
FGF2
Uniprot ID:
P09038
Molecular Weight:
30769.715 Da
References
  1. Sehgal SN: Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003 May;35(3 Suppl):7S-14S. [PubMed:12742462 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [PubMed:10490933 ]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitorinducer
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Schuetz EG, Beck WT, Schuetz JD: Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8. [PubMed:8632764 ]
  2. Wacher VJ, Silverman JA, Wong S, Tran-Tau P, Chan AO, Chai A, Yu XQ, O'Mahony D, Ramtoola Z: Sirolimus oral absorption in rats is increased by ketoconazole but is not affected by D-alpha-tocopheryl poly(ethylene glycol 1000) succinate. J Pharmacol Exp Ther. 2002 Oct;303(1):308-13. [PubMed:12235265 ]
  3. Arceci RJ, Stieglitz K, Bierer BE: Immunosuppressants FK506 and rapamycin function as reversal agents of the multidrug resistance phenotype. Blood. 1992 Sep 15;80(6):1528-36. [PubMed:1381629 ]
  4. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. Fehrenbach T, Cui Y, Faulstich H, Keppler D: Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Naunyn Schmiedebergs Arch Pharmacol. 2003 Nov;368(5):415-20. Epub 2003 Oct 3. [PubMed:14530907 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport...
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
References
  1. Meyer zu Schwabedissen HE, Verstuyft C, Kroemer HK, Becquemont L, Kim RB: Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005. doi: 10.1152/ajprenal.00431.2009. Epub 2010 Jan 6. [PubMed:20053795 ]
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Drug created on June 13, 2005 07:24 / Updated on June 27, 2016 03:07