Details of the Drug
General Information of Drug (ID: DMS104F)
Drug Name |
Temsirolimus
|
|||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Synonyms | Torisel | |||||||||||||||||||
Indication |
|
|||||||||||||||||||
Drug Type |
Small molecular drug
|
|||||||||||||||||||
Structure | ||||||||||||||||||||
3D MOL is unavailable | 2D MOL | |||||||||||||||||||
#Ro5 Violations (Lipinski): 4 | Molecular Weight (mw) | 1030.3 | ||||||||||||||||||
Topological Polar Surface Area (xlogp) | 5.6 | |||||||||||||||||||
Rotatable Bond Count (rotbonds) | 11 | |||||||||||||||||||
Hydrogen Bond Donor Count (hbonddonor) | 4 | |||||||||||||||||||
Hydrogen Bond Acceptor Count (hbondacc) | 16 | |||||||||||||||||||
ADMET Property |
|
|||||||||||||||||||
Chemical Identifiers |
|
|||||||||||||||||||
Cross-matching ID | ||||||||||||||||||||
Molecular Interaction Atlas of This Drug
Drug Therapeutic Target (DTT) |
|
||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Drug Transporter (DTP) |
|
||||||||||||||||||||||||||||||||||||
Drug-Metabolizing Enzyme (DME) |
|
||||||||||||||||||||||||||||||||||||
Molecular Interaction Atlas (MIA) | |||||||||||||||||||||||||||||||||||||
Molecular Expression Atlas of This Drug
The Studied Disease | Renal cell carcinoma | |||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ICD Disease Classification | 2C90 | |||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||
Molecular Expression Atlas (MEA) | ||||||||||||||||||||||||||||||||||||||||||
Drug-Drug Interaction (DDI) Information of This Drug
Coadministration of a Drug Treating the Disease Different from Temsirolimus (Comorbidity)
|
Drug Inactive Ingredient(s) (DIG) and Formulation(s) 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 | Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20. | ||||
3 | BDDCS applied to over 900 drugs | ||||
4 | An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9. | ||||
5 | Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds | ||||
6 | FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41. | ||||
7 | 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 | ||||
8 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | ||||
9 | 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. | ||||
10 | Drug Interactions Flockhart Table | ||||
11 | Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65. | ||||
12 | Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47. | ||||
13 | Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. | ||||
14 | Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9. | ||||
15 | Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772. | ||||
16 | Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98. | ||||
17 | Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6. | ||||
18 | The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76. | ||||
19 | Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. | ||||
20 | Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95. | ||||
21 | Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81. | ||||
22 | Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72. | ||||
23 | Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8. | ||||
24 | Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8. | ||||
25 | Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94. | ||||
26 | Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000. | ||||
27 | Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71. | ||||
28 | The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7. | ||||
29 | Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. | ||||
30 | Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66. | ||||
31 | The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94. | ||||
32 | Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007. | ||||
33 | MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8. | ||||
34 | Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64. | ||||
35 | Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31. | ||||
36 | Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. | ||||
37 | Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. | ||||
38 | Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50. | ||||
39 | Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51. | ||||
40 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | ||||
41 | 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. | ||||
42 | 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. (Target id: 2109). | ||||
43 | Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516. | ||||
44 | A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8. | ||||
45 | Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12. | ||||
46 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | ||||
47 | Cerner Multum, Inc. "Australian Product Information.". | ||||
48 | Product Information. Myalept (metreleptin). Bristol-Myers Squibb, Princeton, NJ. | ||||
49 | Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL. | ||||
50 | Cerner Multum, Inc. "UK Summary of Product Characteristics.". | ||||
51 | Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA. | ||||
52 | Product Information. Torisel (temsirolimus). Wyeth-Ayerst Laboratories, Philadelphia, PA. | ||||
53 | Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO. | ||||
54 | Product Information. Zurampic (lesinurad). Astra-Zeneca Pharmaceuticals, Wilmington, DE. | ||||
55 | Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA. | ||||
56 | Product Information. Blincyto (blinatumomab). Amgen USA, Thousand Oaks, CA. | ||||
57 | Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO. | ||||
58 | Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA. | ||||
59 | Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ. | ||||
60 | Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA. | ||||
61 | Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ. | ||||
62 | Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA. | ||||
63 | Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA. | ||||
64 | 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] | ||||
65 | 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] | ||||
66 | Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA. | ||||