Drug Details

General Information of the Drug (ID: DR4137)
Name
Rapamycin
Synonyms
(-)-Rapamycin; 53123-88-9; AY 22989; AY-22989; I 2190A; I-2190A; I2190A; NSC 226080; RAPA; Rapammune; Rapamune; Rapamycin; SIIA 9268A; Sirolimus; Wy 090217; Rapamycin (Sirolimus); Antibiotic AY 22989; UNII-W36ZG6FT64; CHEBI:9168; W36ZG6FT64; WY-090217; DE-109; MFCD00867594; NCGC00021305-05; DSSTox_CID_3582; DSSTox_RID_77091; DSSTox_GSID_23582; SILA 9268A; Supralimus; CAS-53123-88-9; sirolimusum; Perceiva; Cypher; CCRIS 9024; NSC226080; HSDB 7284; 1fkb; 1pbk; NSC-226080; NCGC00181146-01; LCP-Siro; RAP; S1039; PubChem16645; BiomolKI2_000084; Rapamycin C-7, analog 4; SCHEMBL3463; Rapamycin,Sirolimus,Rapamune; BIDD:PXR0165; 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine; MLS006010168; Sirolimus [USAN:INN:BAN]; GTPL6031; DTXSID5023582; BDBM36609; L04AA10; MS-R001; SYN1185; SM-88 COMPONENT SIROLIMUS; HMS2089A21; HMS3403F11; HMS3884C03; (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; EX-A1044; Tox21_110870; Tox21_112750; AC-722; BDBM50064359; STL570275; AKOS015850976; AKOS015961618; ZINC169289388; ACN-035837; CCG-100684; CS-0063; DB00877; NCGC00021305-06; NCGC00021305-07; Rapamycin from Streptomyces hygroscopicus; AS-11687; HY-10219; SMR004701276; UNM-0000358684; A-275; R0097; Rapamycin, RAPA, Rapamune, Sirolimus, RPM; Rapamycin, VETRANAL(TM), analytical standard; EC 610-965-5; Q32089; S-7759; 123R889; Q-201659;
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Molecular Type
Small molecule
Disease Multiple myeloma [ICD-11: 2A83] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C51H79NO13
PubChem CID
5284616
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)O)C)C)O)OC)C)C)C)OC
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
InChIKey
QFJCIRLUMZQUOT-HPLJOQBZSA-N
CAS Number
CAS 53123-88-9
ChEBI ID
CHEBI:9168
GDSC
Rapamycin
TTD Drug ID
D0T6DK
DrugBank ID
DB00877
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Asiaticoside      Centella asiatica     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 TGFB1  Molecule Info 
Pathway MAP
                    In-vitro Model Human aortic smooth muscle cell Healthy Homo sapiens
Human aortic fibroblasts Healthy Homo sapiens
Human coronary artery endothelial cells Healthy Homo sapiens
                    Experimental
                    Result(s)		 Asiaticoside combined with rapamycin may be effective in the reduction of ISR.
          Elemene      Pogostemon cablin     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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
                    In-vitro Model FTC-133 CVCL_1219 Thyroid gland follicular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The novel combination of mTOR inhibitor with Beta-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation.
          Honokiol      Magnolia officinalis     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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PD-L1  Molecule Info 
Pathway MAP
                    In-vitro Model 786-O CVCL_1051 Renal cell carcinoma Homo sapiens
ACHN CVCL_1067 Papillary renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Honokiol can effectively overcome the limitation of Rapamycin treatment alone, and the combination treatment can markedly restrict the growth of RCC, with particular importance to post-transplantation renal cancer.
          Metformin      Galega officinalis     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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model The in vovo experiment was carried out with male Wistar rats.
                    Experimental
                    Result(s)		 Cotreatment with rapamycin and metformin showed a significant augmented effect compared with individual drug interventions on reversal of these age-dependent biomarkers of oxidative stress, suggesting a synergistic response.
          Mycophenolate mofetil      Penicillium stoloniferum     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 [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model The left kidney of the donor rat (Fisher F344) was perfused through the aorta with 4 degree centigrade heparinized Ringer's lactate solution and harvested, after transecting the ureter, the renal artery close to the aorta, and the renal vein near the vena cava. The recipient rat was anesthetized and a left nephrectomy was performed after transecting the renal artery, the renal vein, and the ureter.
                    Experimental
                    Result(s)		 Over a 50-week study, concomitant therapy of MMF and RAPA prevents chronic renal allograft rejection, probably through reduction of ischemic and cytotoxic degenerative changes.
          Resveratrol      Gnetum parvifolium     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 [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation S6K1  Molecule Info 
Pathway MAP
                    In-vitro Model KTC-1 CVCL_6300 Thyroid gland carcinoma Homo sapiens
TPC-1 CVCL_6298 Thyroid gland papillary carcinoma Homo sapiens
                    In-vivo Model KTC-1 and TPC-1 cells in logarithmic growth phase were subcutaneously inoculated into the right armpit of Nude BALB/c mice (5*106 cells/mouse).
                    Experimental
                    Result(s)		 Resveratrol sensitizes the anti-tumor effects of rapamycin and the PI3K/AKT/mTOR signaling is involved.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Daunorubicin      Streptomyces peucetius     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model SUP-B15 CVCL_0103 B acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 RAPA effectively eliminated this deleterious side effect of DNR, which might enhance DNR's ability to kill drug-resistant cancer.
    γ. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Arsenic trioxide      Realgar and orpiment     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
T-47D CVCL_0553 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Arsenic trioxide overcomes rapamycin-induced feedback activation of AKT and ERK signaling to enhance the anti-tumor effects in breast cancer.
Target and Pathway
Target(s) FK506-binding protein 1A (FKBP1A)  Molecule Info  [10]
Opioid receptor kappa (KOR)  Molecule Info  [11]
Serine/threonine-protein kinase mTOR (mTOR)  Molecule Info  [12]
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
18 Neuroactive ligand-receptor interaction
Panther Pathway Hypoxia response via HIF activation Click to Show/Hide
2 Interleukin signaling pathway
3 Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
4 Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
5 Opioid prodynorphin 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
9 Peptide ligand-binding receptors
10 G alpha (i) signalling events
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
30 GPCRs, Class A Rhodopsin-like
31 Peptide GPCRs
32 GPCR ligand binding
33 GPCR downstream signaling
References
Reference 1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Reference 2 Combination treatment with asiaticoside and rapamycin: A new hope for in-stent restenosis. Exp Ther Med. 2013 Aug;6(2):557-561.
Reference 3 Combinatorial Antitumor Effect of Rapamycin and Beta-Elemene in Follicular Thyroid Cancer Cells. Biomed Res Int. 2016;2016:6723807.
Reference 4 A Novel Combination Treatment with Honokiol and Rapamycin Effectively Restricts c-Met-Induced Growth of Renal Cancer Cells, and also Inhibits the Expression of Tumor Cell PD-L1 Involved in Immune Escape. Cancers (Basel). 2020 Jul 3;12(7):1782.
Reference 5 Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative Stress in Rat Erythrocytes. Rejuvenation Res. 2017 Oct;20(5):420-429.
Reference 6 Combination therapy of mycophenolate mofetil and rapamycin in prevention of chronic renal allograft rejection in the rat. Transplantation. 2003 Jan 15;75(1):54-9.
Reference 7 Resveratrol potentiates the anti-tumor effects of rapamycin in papillary thyroid cancer: PI3K/AKT/mTOR pathway involved. Arch Biochem Biophys. 2020 Aug 15;689:108461.
Reference 8 Antileukaemia effect of rapamycin alone or in combination with daunorubicin on Ph+ acute lymphoblastic leukaemia cell line. Hematol Oncol. 2012 Sep;30(3):123-30.
Reference 9 Arsenic trioxide overcomes rapamycin-induced feedback activation of AKT and ERK signaling to enhance the anti-tumor effects in breast cancer. PLoS One. 2013 Dec 31;8(12):e85995.
Reference 10 Neural roles of immunophilins and their ligands. Mol Neurobiol. 1997 Oct;15(2):223-39.
Reference 11 The 12 kD FK 506 binding protein FKBP12 is released in the male reproductive tract and stimulates sperm motility. Mol Med. 1998 Aug;4(8):502-14.
Reference 12 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
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