Details of the Drug

General Information of Drug (ID: DMS104F)

Drug Name
Temsirolimus
Synonyms Torisel
Indication
Disease Entry ICD 11 Status REF
Renal cell carcinoma 2C90 Approved [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 4 Molecular Weight (mw) 1030.3
Logarithm of the Partition Coefficient (xlogp) 5.6
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 16
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Clearance
The clearance of drug is 16.2 L/h []
Elimination
4.6% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 17.3 hours (temsirolimus), and 54.6 hours (sirolimus) [3]
Metabolism
The drug is metabolized via the cytochrome P450 3A4 in the human liver []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.14767 micromolar/kg/day [4]
Vd
The volume of distribution (Vd) of drug is 172 L []
Water Solubility
The ability of drug to dissolve in water is measured as 0.01 mg/mL [2]
Chemical Identifiers
Formula
C56H87NO16
IUPAC Name
[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl] 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate
Canonical SMILES
C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)OC(=O)C(C)(CO)CO)C)/C)O)OC)C)C)/C)OC
InChI
InChI=1S/C56H87NO16/c1-33-17-13-12-14-18-34(2)45(68-9)29-41-22-20-39(7)56(67,73-41)51(63)52(64)57-24-16-15-19-42(57)53(65)71-46(30-43(60)35(3)26-38(6)49(62)50(70-11)48(61)37(5)25-33)36(4)27-40-21-23-44(47(28-40)69-10)72-54(66)55(8,31-58)32-59/h12-14,17-18,26,33,35-37,39-42,44-47,49-50,58-59,62,67H,15-16,19-25,27-32H2,1-11H3/b14-12+,17-13+,34-18+,38-26+/t33-,35-,36-,37-,39-,40+,41+,42+,44-,45+,46+,47-,49-,50+,56-/m1/s1
InChIKey
CBPNZQVSJQDFBE-FUXHJELOSA-N
Cross-matching ID
PubChem CID
6918289
ChEBI ID
CHEBI:79699
CAS Number
162635-04-3
DrugBank ID
DB06287
TTD ID
D0ES1Q
VARIDT ID
DR00432
INTEDE ID
DR1548
ACDINA ID
D01471
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [7]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Renal cell carcinoma
ICD Disease Classification 2C90
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Serine/threonine-protein kinase mTOR (mTOR) DTT MTOR 2.16E-05 -0.44 -2.3
P-glycoprotein 1 (ABCB1) DTP P-GP 2.04E-02 -1.13E+00 -1.00E+00
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 3.51E-02 1.53E+00 1.16E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.84E-01 -1.61E-01 -3.61E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Temsirolimus (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Decreased renal excretion of Temsirolimus caused by Remdesivir mediated nephrotoxicity. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [8]
Metreleptin DM1NOEK Moderate Decreased metabolism of Temsirolimus caused by Metreleptin mediated inhibition of CYP450 enzyme. Acute diabete complication [5A2Y] [9]
Ivosidenib DM8S6T7 Moderate Increased metabolism of Temsirolimus caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [8]
Arn-509 DMT81LZ Major Increased metabolism of Temsirolimus caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [8]
Oliceridine DM6MDCF Moderate Increased plasma concentrations of Temsirolimus and Oliceridine due to competitive inhibition of the same metabolic pathway. Acute pain [MG31] [10]
Inotersen DMJ93CT Major Increased risk of nephrotoxicity by the combination of Temsirolimus and Inotersen. Amyloidosis [5D00] [11]
Siltuximab DMGEATB Moderate Additive myelosuppressive effects by the combination of Temsirolimus and Siltuximab. Anemia [3A00-3A9Z] [11]
Troleandomycin DMUZNIG Major Increased metabolism of Temsirolimus caused by Troleandomycin mediated induction of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [8]
Erdafitinib DMI782S Moderate Increased metabolism of Temsirolimus caused by Erdafitinib mediated induction of CYP450 enzyme. Bladder cancer [2C94] [12]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Temsirolimus caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [8]
Tucatinib DMBESUA Major Increased metabolism of Temsirolimus caused by Tucatinib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [8]
Palbociclib DMD7L94 Moderate Decreased metabolism of Temsirolimus caused by Palbociclib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [13]
Cabazitaxel DMPAZHC Moderate Increased plasma concentrations of Temsirolimus and Cabazitaxel due to competitive inhibition of the same metabolic pathway. Breast cancer [2C60-2C6Y] [10]
Levonorgestrel DM1DP7T Moderate Increased plasma concentrations of Temsirolimus and Levonorgestrel due to competitive inhibition of the same metabolic pathway. Contraceptive management [QA21] [10]
Lumacaftor DMCLWDJ Major Increased metabolism of Temsirolimus caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [8]
Ivacaftor DMZC1HS Moderate Decreased metabolism of Temsirolimus caused by Ivacaftor mediated inhibition of CYP450 enzyme. Cystic fibrosis [CA25] [13]
OPC-34712 DMHG57U Moderate Increased plasma concentrations of Temsirolimus and OPC-34712 due to competitive inhibition of the same metabolic pathway. Depression [6A70-6A7Z] [10]
Stiripentol DMMSDOY Moderate Decreased metabolism of Temsirolimus caused by Stiripentol mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [13]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Temsirolimus caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [8]
Tazemetostat DMWP1BH Moderate Increased metabolism of Temsirolimus caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [8]
Boceprevir DMBSHMF Major Increased metabolism of Temsirolimus caused by Boceprevir mediated induction of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [8]
177Lu-DOTATATE DMT8GVU Major Increased risk of nephrotoxicity by the combination of Temsirolimus and 177Lu-DOTATATE. Hepatitis virus infection [1E50-1E51] [10]
Cobicistat DM6L4H2 Major Increased metabolism of Temsirolimus caused by Cobicistat mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [8]
Etravirine DMGV8QU Moderate Increased metabolism of Temsirolimus caused by Etravirine mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [8]
Teriflunomide DMQ2FKJ Major Additive myelosuppressive effects by the combination of Temsirolimus and Teriflunomide. Hyper-lipoproteinaemia [5C80] [14]
BMS-201038 DMQTAGO Moderate Decreased metabolism of Temsirolimus caused by BMS-201038 mediated inhibition of CYP450 enzyme. Hyper-lipoproteinaemia [5C80] [13]
Levamlodipine DM92S6N Moderate Decreased metabolism of Temsirolimus caused by Levamlodipine mediated inhibition of CYP450 enzyme. Hypertension [BA00-BA04] [8]
Givosiran DM5PFIJ Major Increased risk of nephrotoxicity by the combination of Temsirolimus and Givosiran. Inborn porphyrin/heme metabolism error [5C58] [10]
Lesinurad DMUR64T Moderate Increased metabolism of Temsirolimus caused by Lesinurad mediated induction of CYP450 enzyme. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [15]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Temsirolimus caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [13]
Suvorexant DM0E6S3 Moderate Decreased metabolism of Temsirolimus caused by Suvorexant mediated inhibition of CYP450 enzyme. Insomnia [7A00-7A0Z] [13]
Glycerol phenylbutyrate DMDGRQO Moderate Increased metabolism of Temsirolimus caused by Glycerol phenylbutyrate mediated induction of CYP450 enzyme. Liver disease [DB90-DB9Z] [11]
Denosumab DMNI0KO Moderate Additive myelosuppressive effects by the combination of Temsirolimus and Denosumab. Low bone mass disorder [FB83] [16]
Crizotinib DM4F29C Moderate Decreased metabolism of Temsirolimus caused by Crizotinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [13]
Brigatinib DM7W94S Moderate Increased metabolism of Temsirolimus caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [8]
Ceritinib DMB920Z Major Increased metabolism of Temsirolimus caused by Ceritinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [8]
PF-06463922 DMKM7EW Moderate Increased metabolism of Temsirolimus caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [8]
Osimertinib DMRJLAT Moderate Decreased metabolism of Temsirolimus caused by Osimertinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [11]
Selpercatinib DMZR15V Moderate Decreased metabolism of Temsirolimus caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [13]
Idelalisib DM602WT Major Increased metabolism of Temsirolimus caused by Idelalisib mediated induction of CYP450 enzyme. Mature B-cell leukaemia [2A82] [8]
Moxetumomab pasudotox DMN63DZ Major Increased risk of nephrotoxicity by the combination of Temsirolimus and Moxetumomab pasudotox. Mature B-cell leukaemia [2A82] [10]
IPI-145 DMWA24P Moderate Decreased metabolism of Temsirolimus caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [13]
Blinatumomab DMGECIJ Moderate Decreased metabolism of Temsirolimus caused by Blinatumomab mediated inhibition of CYP450 enzyme. Mature B-cell lymphoma [2A85] [17]
Vemurafenib DM62UG5 Moderate Increased metabolism of Temsirolimus caused by Vemurafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [8]
LGX818 DMNQXV8 Moderate Increased metabolism of Temsirolimus caused by LGX818 mediated induction of CYP450 enzyme. Melanoma [2C30] [18]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Temsirolimus caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [8]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Temsirolimus and Tecfidera. Multiple sclerosis [8A40] [19]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Temsirolimus and Siponimod. Multiple sclerosis [8A40] [8]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Temsirolimus and Fingolimod. Multiple sclerosis [8A40] [20]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Temsirolimus and Ocrelizumab. Multiple sclerosis [8A40] [21]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Temsirolimus and Ozanimod. Multiple sclerosis [8A40] [11]
Deflazacort DMV0RNS Moderate Increased plasma concentrations of Temsirolimus and Deflazacort due to competitive inhibition of the same metabolic pathway. Muscular dystrophy [8C70] [10]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Temsirolimus caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [13]
Netupitant DMEKAYI Moderate Decreased metabolism of Temsirolimus caused by Netupitant mediated inhibition of CYP450 enzyme. Nausea/vomiting [MD90] [13]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Temsirolimus caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [13]
Abametapir DM2RX0I Moderate Decreased metabolism of Temsirolimus caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [22]
Lefamulin DME6G97 Moderate Decreased metabolism of Temsirolimus caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [23]
Lonafarnib DMGM2Z6 Major Increased metabolism of Temsirolimus caused by Lonafarnib mediated induction of CYP450 enzyme. Premature ageing appearance [LD2B] [8]
Enzalutamide DMGL19D Major Increased metabolism of Temsirolimus caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [8]
Tildrakizumab DMLW9HG Moderate Additive immunosuppressive effects by the combination of Temsirolimus and Tildrakizumab. Psoriasis [EA90] [11]
Risankizumab DMM32GT Moderate Additive myelosuppressive effects by the combination of Temsirolimus and Risankizumab. Psoriasis [EA90] [11]
Ixekizumab DMXW92T Moderate Additive myelosuppressive effects by the combination of Temsirolimus and Ixekizumab. Psoriasis [EA90] [11]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Temsirolimus and Rilonacept. Rheumatoid arthritis [FA20] [11]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Temsirolimus and Golimumab. Rheumatoid arthritis [FA20] [24]
Sarilumab DMOGNXY Moderate Additive myelosuppressive effects by the combination of Temsirolimus and Sarilumab. Rheumatoid arthritis [FA20] [11]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Temsirolimus when combined with Anthrax vaccine. Sepsis [1G40-1G41] [25]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Temsirolimus caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [13]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Temsirolimus caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [11]
Larotrectinib DM26CQR Moderate Decreased metabolism of Temsirolimus caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [13]
Armodafinil DMGB035 Minor Increased metabolism of Temsirolimus caused by Armodafinil mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [26]
LEE011 DMMX75K Moderate Decreased metabolism of Temsirolimus caused by LEE011 mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [13]
Telavancin DM58VQX Major Increased risk of nephrotoxicity by the combination of Temsirolimus and Telavancin. Staphylococcal/streptococcal disease [1B5Y] [10]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Temsirolimus caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [27]
Plazomicin DMKMBES Major Increased risk of nephrotoxicity by the combination of Temsirolimus and Plazomicin. Urinary tract infection [GC08] [10]
Elagolix DMB2C0E Moderate Increased metabolism of Temsirolimus caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [8]
⏷ Show the Full List of 75 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
DL-alpha-tocopherol E00052 2116 Antioxidant
Kyselina citronova E00014 311 Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Ethanol E00023 702 Antimicrobial preservative; Penetration agent; Solvent
Polyethylene glycol 400 E00653 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80 E00665 Not Available Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
⏷ Show the Full List of 6 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Temsirolimus 25mg/ml solution 25mg/ml Solution Intravenous
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5892).
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
6 Association of NR1I2, CYP3A5 and ABCB1 genetic polymorphisms with variability of temsirolimus pharmacokinetics and toxicity in patients with metastatic bladder cancer. Cancer Chemother Pharmacol. 2017 Sep;80(3):653-659.
7 Drug Interactions Flockhart Table
8 Cerner Multum, Inc. "Australian Product Information.".
9 Product Information. Myalept (metreleptin). Bristol-Myers Squibb, Princeton, NJ.
10 Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
11 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
12 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
13 Product Information. Torisel (temsirolimus). Wyeth-Ayerst Laboratories, Philadelphia, PA.
14 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
15 Product Information. Zurampic (lesinurad). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
16 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
17 Product Information. Blincyto (blinatumomab). Amgen USA, Thousand Oaks, CA.
18 Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
19 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
20 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
21 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
22 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
23 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
24 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
25 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
26 Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53. [PMID: 11978143]
27 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.