Drug Details

General Information of the Drug (ID: DR9647)
Name
Temsirolimus
Synonyms
Temsirolimus; CCI-779; Torisel; 162635-04-3; UNII-624KN6GM2T; 624KN6GM2T; CHEMBL1201182; 42-[3-Hydroxy-2-methylpropanoate; MFCD00934421; NCGC00167518-01; Cci 779; Rapamycin 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]; Temsirolimus (CCI-779, NSC 683864); CHEBI:79699; Temserolimus; NSC-683864; Temsirolimus - Torisel; Rapamycin 42-(2,2-bis(hydroxymethyl)propionate); Temsirolimus(CCI-779); DSSTox_CID_20945; DSSTox_RID_79605; DSSTox_GSID_40945; SCHEMBL18792; 42-(3-Hydroxy-2-(hydroxymethyl)-2-methylpropanoate)rapamycin; WAY-CCI 779; GTPL5892; DTXSID2040945; HSDB 7931; Temsirolimus, >=98% (HPLC); C56H87NO16; AOB87306; Temsirolimus [USAN:INN:BAN:JAN]; Tox21_112515; BDBM50343413; s1044; AKOS025142069; AM84554; CCG-264790; CS-0129; NCGC00167518-02; NCGC00167518-05; NCGC00167518-09; HY-50910; CAS-162635-04-3; T3574; AB01274736-01; AB01274736_02; 635T043; SR-01000898799; J-009958; Q7699074; SR-01000898799-3; BRD-K08177763-001-02-6; 42-[3-Hydroxy-2-(hydroxymethyl)-2-methylpropanoate]-rapamycin; Rapamycin, 42-(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate)
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Molecular Type
Small molecule
Disease Renal cell carcinoma [ICD-11: 2C90] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability
Clearance
The clearance of drug is 16.2 L/h
Elimination
4.6% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 17.3 hours (temsirolimus), and 54.6 hours (sirolimus)
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
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
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Formula
C56H87NO16
PubChem CID
6918289
Canonical SMILES
CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OC(=O)C(C)(CO)CO)C)C)O)OC)C)C)C)OC
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
CAS Number
CAS 162635-04-3
ChEBI ID
CHEBI:79699
TTD Drug ID
D0ES1Q
DrugBank ID
DB06287
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Vinblastine      Catharanthus roseus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression EIF4EBP1  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression S6K1  Molecule Info 
Pathway MAP
                    In-vitro Model Hep 3B2.1-7 CVCL_0326 Childhood hepatocellular carcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
SNU-398 CVCL_0077 Adult hepatocellular carcinoma Homo sapiens
                    In-vivo Model HCC cells (2 * 106 of Huh7 cells or 3 * 106 of Hep3B cells suspended in 200 ul serum free medium) were inoculated into the dorsal flanks of male athymic nude mice (nu/nu) by subcutaneous injection.
                    Experimental
                    Result(s)		 The potent anti-cancer activity of this co-targeting strategy was indeed mediated in parts by inhibition of these key survival/anti-apoptotic proteins.
Target and Pathway
Target(s) Serine/threonine-protein kinase mTOR (mTOR)  Molecule Info  [3]
KEGG Pathway ErbB signaling pathway Click to Show/Hide
2 HIF-1 signaling pathway
3 mTOR signaling pathway
4 PI3K-Akt signaling pathway
5 AMPK signaling pathway
6 Insulin signaling pathway
7 Thyroid hormone signaling pathway
8 Adipocytokine signaling pathway
9 Type II diabetes mellitus
10 Pathways in cancer
11 Proteoglycans in cancer
12 MicroRNAs in cancer
13 Glioma
14 Prostate cancer
15 Acute myeloid leukemia
16 Central carbon metabolism in cancer
17 Choline metabolism in cancer
Panther Pathway Hypoxia response via HIF activation Click to Show/Hide
2 Interleukin signaling pathway
Pathwhiz Pathway Leucine Stimulation on Insulin Signaling Click to Show/Hide
Pathway Interaction Database IL4-mediated signaling events Click to Show/Hide
2 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
3 IL12-mediated signaling events
4 CDC42 signaling events
5 LKB1 signaling events
6 Regulation of Telomerase
7 mTOR signaling pathway
8 CXCR4-mediated signaling events
9 EGFR-dependent Endothelin signaling events
10 IL2 signaling events mediated by PI3K
11 IFN-gamma pathway
12 ErbB1 downstream signaling
13 ErbB2/ErbB3 signaling events
14 CXCR3-mediated signaling events
15 Class I PI3K signaling events mediated by Akt
Reactome PIP3 activates AKT signaling Click to Show/Hide
2 Macroautophagy
3 mTORC1-mediated signalling
4 HSF1-dependent transactivation
5 CD28 dependent PI3K/Akt signaling
6 VEGFR2 mediated vascular permeability
7 TP53 Regulates Metabolic Genes
8 Constitutive Signaling by AKT1 E17K in Cancer
WikiPathways ErbB Signaling Pathway Click to Show/Hide
2 Senescence and Autophagy in Cancer
3 Interferon type I signaling pathways
4 Insulin Signaling
5 EGF/EGFR Signaling Pathway
6 Wnt Signaling Pathway Netpath
7 Extracellular vesicle-mediated signaling in recipient cells
8 Cardiac Hypertrophic Response
9 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
10 PIP3 activates AKT signaling
11 Polycystic Kidney Disease Pathway
12 Alpha 6 Beta 4 signaling pathway
13 BDNF signaling pathway
14 Oncostatin M Signaling Pathway
15 Prostate Cancer
16 TSLP Signaling Pathway
17 FSH signaling pathway
18 Leptin signaling pathway
19 TSH signaling pathway
20 RANKL/RANK Signaling Pathway
21 SREBF and miR33 in cholesterol and lipid homeostasis
22 Integrated Breast Cancer Pathway
23 SREBP signalling
24 Signaling by Insulin receptor
25 Costimulation by the CD28 family
26 Type II diabetes mellitus
27 MicroRNAs in cardiomyocyte hypertrophy
28 TOR Signaling
29 AMPK Signaling
References
Reference 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).
Reference 2 Sustained antitumor activity by co-targeting mTOR and the microtubule with temsirolimus/vinblastine combination in hepatocellular carcinoma. Biochem Pharmacol. 2012 May 1;83(9):1146-58.
Reference 3 Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
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