DGIdb - SIROLIMUS Drug Record

SIROLIMUS chembl:CHEMBL413 ApprovedAntineoplasticImmunotherapy

Alternate Names:

RAPAMYCIN
SIROLIMUS
L04AA10
RAPAMUNE
SM-88 COMPONENT SIROLIMUS
AY-22989
WY-090217
NSC-226080
(-)-RAPAMYCIN
drugbank:00877
chembl:CHEMBL413
pubchem.compound:5284616
rxcui:35302
chemidplus:53123-88-9

Drug Info:

Notes	rapalogue
Drug Class	Kinase Inhibitors
Drug Indications	for treatment of wet age-related macular degeneration
FDA Approval	approved
Drug Class	Small Molecule
Drug Indications	immunosuppressant
Drug Categories	hyperglycemia-associated agents
Drug Class	immunosuppressive agents
Year of Approval	2007
Drug Categories	agents causing angioedema
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 cyp3a5 substrates
Drug Categories	cytochrome p-450 cyp3a5 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 cyp3a7 substrates
Drug Categories	cytochrome p-450 cyp3a7 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 substrates
Drug Categories	decreased immunologic activity
Drug Categories	kinase inhibitor
Drug Categories	mtor inhibitor immunosuppressant
Drug Categories	mtor inhibitors
Drug Categories	narrow therapeutic index drugs
Drug Categories	oatp1b1/slco1b1 inhibitors
Drug Categories	ophthalmologicals
Drug Categories	p-glycoprotein inducers
Drug Categories	p-glycoprotein inhibitors
Drug Categories	p-glycoprotein substrates
Drug Categories	p-glycoprotein substrates with narrow therapeutic index
Drug Categories	protein kinase inhibitors
Drug Categories	sensory organs
Drug Categories	sirolimus and prodrugs

(17 More Sources)

Publications:

Nardacci et al., 2005, Characterization of cell death pathways in human immunodeficiency virus-associated encephalitis., Am. J. Pathol.
Yamaguchi et al., 2016, A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers., Oncotarget
Purdom-Dickinson et al., 2007, Translational control of nrf2 protein in activation of antioxidant response by oxidants., Mol. Pharmacol.
Jardim et al., 2014, FBXW7 mutations in patients with advanced cancers: clinical and molecular characteristics and outcomes with mTOR inhibitors., PLoS ONE
Mao et al., 2008, FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression., Science
Wang et al., 2013, Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells., Biochem. Biophys. Res. Commun.
Nepomuceno et al., 2003, Rapamycin inhibits the interleukin 10 signal transduction pathway and the growth of Epstein Barr virus B-cell lymphomas., Cancer Res.
Sam WJ et al., 2011, Associations of ABCB1 3435C>T and IL-10-1082G>A polymorphisms with long-term sirolimus dose requirements in renal transplant patients., Transplantation
Woillard JB et al., 2013, Effect of CYP3A422, POR28, and PPARA rs4253728 on sirolimus in vitro metabolism and trough concentrations in kidney transplant recipients., Clin Chem
Liang et al., 2010, TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity., Oncogene
Kang et al., 2005, Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic., Proc. Natl. Acad. Sci. U.S.A.
Avellino et al., 2005, Rapamycin stimulates apoptosis of childhood acute lymphoblastic leukemia cells., Blood
Zick et al., 2017, Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients., Medicine (Baltimore)
Engelman et al., 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers., Nat. Med.
Gymnopoulos et al., 2007, Rare cancer-specific mutations in PIK3CA show gain of function., Proc. Natl. Acad. Sci. U.S.A.
Mavrakis et al., 2008, Tumorigenic activity and therapeutic inhibition of Rheb GTPase., Genes Dev.
Sehgal, 2003, Sirolimus: its discovery, biological properties, and mechanism of action., Transplant. Proc.
Du L et al., 2014, Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum., J Nat Prod
Salomé C et al., 2014, Benzofuran derivatives as anticancer inhibitors of mTOR signaling., Eur J Med Chem
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Nowak P et al., 2009, Discovery of potent and selective inhibitors of the mammalian target of rapamycin (mTOR) kinase., J Med Chem
Grabiner et al., 2014, A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity., Cancer Discov
Dowling et al., 2010, Dissecting the role of mTOR: lessons from mTOR inhibitors., Biochim. Biophys. Acta
Xu et al., 2016, Mechanistically distinct cancer-associated mTOR activation clusters predict sensitivity to rapamycin., J. Clin. Invest.
Rodrik-Outmezguine et al., 2016, Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor., Nature
Pratt MR et al., 2007, Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt., Proc Natl Acad Sci U S A
Shuuin et al., 2009, [Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma]., Gan To Kagaku Ryoho
Lovly et al., 2011, Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors., Cancer Res.
Palm et al., 2015, The Utilization of Extracellular Proteins as Nutrients Is Suppressed by mTORC1., Cell
Mungamuri et al., 2006, Survival signaling by Notch1: mammalian target of rapamycin (mTOR)-dependent inhibition of p53., Cancer Res.
Contreras et al., Lkb1 inactivation is sufficient to drive endometrial cancers that are aggressive yet highly responsive to mTOR inhibitor monotherapy., Dis Model Mech
Brown et al., 2003, Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signaling., Proc. Natl. Acad. Sci. U.S.A.
Ganesan et al., 2016, Epidermal Growth Factor Receptor P753S Mutation in Cutaneous Squamous Cell Carcinoma Responsive to Cetuximab-Based Therapy., J. Clin. Oncol.
Pirazzoli et al., 2014, Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1., Cell Rep
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Engelman et al., 2007, PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib., Cancer Res.
Mbatchi LC et al., 2017, Association of NR1I2, CYP3A5 and ABCB1 genetic polymorphisms with variability of temsirolimus pharmacokinetics and toxicity in patients with metastatic bladder cancer., Cancer Chemother Pharmacol
Woillard JB et al., 2010, Risk of diarrhoea in a long-term cohort of renal transplant patients given mycophenolate mofetil: the significant role of the UGT1A8 2 variant allele., Br J Clin Pharmacol
Aoki et al., 2006, mTOR pathway inhibition attenuates skeletal muscle growth induced by stretching., Cell Tissue Res.
Maertens et al., 2013, Elucidating distinct roles for NF1 in melanomagenesis., Cancer Discov
Pawarode et al., 2007, Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus and sirolimus on drug transport by multidrug resistance proteins., Cancer Chemother. Pharmacol.
Wei et al., 2006, Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance., Cancer Cell
Dunn et al., 2001, Up-regulation of urokinase-type plasminogen activator by insulin-like growth factor-I depends upon phosphatidylinositol-3 kinase and mitogen-activated protein kinase kinase., Cancer Res.
Chen et al., 1996, The RB/p107/p130 phosphorylation pathway is not inhibited in rapamycin-induced G1-prolongation of NIH3T3 cells., Oncogene
Entingh et al., 2001, Induction of the C/EBP homologous protein (CHOP) by amino acid deprivation requires insulin-like growth factor I, phosphatidylinositol 3-kinase, and mammalian target of rapamycin signaling., Endocrinology
Tirado et al., 2005, Rapamycin induces apoptosis of JN-DSRCT-1 cells by increasing the Bax : Bcl-xL ratio through concurrent mechanisms dependent and independent of its mTOR inhibitory activity., Oncogene
Sam WJ et al., 2012, Associations of ABCB1 and IL-10 genetic polymorphisms with sirolimus-induced dyslipidemia in renal transplant recipients., Transplantation
Cummins et al., 2004, CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam., J. Pharmacol. Exp. Ther.
Lai et al., 1994, CD28 signaling causes a sustained down-regulation of I kappa B alpha which can be prevented by the immunosuppressant rapamycin., J. Biol. Chem.
Vanasek et al., 2001, Antagonistic roles for CTLA-4 and the mammalian target of rapamycin in the regulation of clonal anergy: enhanced cell cycle progression promotes recall antigen responsiveness., J. Immunol.
Fox et al., 2005, The Pim kinases control rapamycin-resistant T cell survival and activation., J. Exp. Med.
Renoir et al., 1992, [Effect of immunosuppressants FK506 and rapamycin on the function of progesterone receptor: protein "p59-HBI", intersection between immunology and endocrinology?]., C. R. Acad. Sci. III, Sci. Vie
Patel et al., 2002, Insulin regulation of hepatic insulin-like growth factor-binding protein-1 (IGFBP-1) gene expression and mammalian target of rapamycin (mTOR) signalling is impaired by the presence of hydrogen peroxide., Biochem. J.
Piña et al., 2011, Advanced retinoblastoma treatment: targeting hypoxia by inhibition of the mammalian target of rapamycin (mTOR) in LH(BETA)T(AG) retinal tumors., Clin Ophthalmol
Livi et al., 2013, Rapamycin extends life span of Rb1+/- mice by inhibiting neuroendocrine tumors., Aging (Albany NY)
Windle et al., 1990, Retinoblastoma in transgenic mice., Nature
Bierer et al., 1990, Probing immunosuppressant action with a nonnatural immunophilin ligand., Science
Tuxworth et al., 1999, Role of load in regulating eIF-4F complex formation in adult feline cardiocytes., Am. J. Physiol.
Feigenblum et al., 1996, Cap-binding protein (eukaryotic initiation factor 4E) and 4E-inactivating protein BP-1 independently regulate cap-dependent translation., Mol. Cell. Biol.
Fraser et al., 1999, Cellular stress in xenopus kidney cells enhances the phosphorylation of eukaryotic translation initiation factor (eIF)4E and the association of eIF4F with poly(A)-binding protein., Biochem. J.
Naegele et al., 2004, Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress., J. Biol. Chem.
Davies et al., 2004, Inhibition of phosphatidylinositol 3-kinase- and ERK MAPK-regulated protein synthesis reveals the pro-apoptotic properties of CD40 ligation in carcinoma cells., J. Biol. Chem.
Fraser et al., 1999, The association of initiation factor 4F with poly(A)-binding protein is enhanced in serum-stimulated Xenopus kidney cells., J. Biol. Chem.
Sanftner et al., 2006, Dimerizer regulation of AADC expression and behavioral response in AAV-transduced 6-OHDA lesioned rats., Mol. Ther.
Duncan et al., 2005, Signal transduction pathways leading to increased eIF4E phosphorylation caused by oxidative stress., Free Radic. Biol. Med.
Hahn-Windgassen et al., 2005, Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity., J. Biol. Chem.
Fujishita et al., 2008, Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in ApcDelta716 mice., Proc. Natl. Acad. Sci. U.S.A.
Hung et al., 2010, Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment., Proc. Natl. Acad. Sci. U.S.A.
Vanaudenaerde et al., 2007, Macrolides inhibit IL17-induced IL8 and 8-isoprostane release from human airway smooth muscle cells., Am. J. Transplant.
Le Meur Y et al., 2006, CYP3A5*3 influences sirolimus oral clearance in de novo and stable renal transplant recipients., Clin Pharmacol Ther
Miao LY et al., 2008, Association study of ABCB1 and CYP3A5 gene polymorphisms with sirolimus trough concentration and dose requirements in Chinese renal transplant recipients., Biopharm Drug Dispos
Li Y et al., 2015, CYP3A5 and ABCB1 genotype influence tacrolimus and sirolimus pharmacokinetics in renal transplant recipients., Springerplus
Rodríguez-Jiménez C et al., 2017, Influence of genetic polymorphisms of CYP3A5 and ABCB1 on sirolimus pharmacokinetics, patient and graft survival and other clinical outcomes in renal transplant., Drug Metab Pers Ther
Emoto C et al., 2015, The impact of CYP3A5*3 polymorphism on sirolimus pharmacokinetics: insights from predictions with a physiologically-based pharmacokinetic model., Br J Clin Pharmacol
Anglicheau D et al., 2005, Consequences of genetic polymorphisms for sirolimus requirements after renal transplant in patients on primary sirolimus therapy., Am J Transplant
Singleton et al., 2015, Kinome RNAi Screens Reveal Synergistic Targeting of MTOR and FGFR1 Pathways for Treatment of Lung Cancer and HNSCC., Cancer Res.
Dubois et al., 2003, Distinct pathways involving the FK506-binding proteins 12 and 12.6 underlie IL-2-versus IL-15-mediated proliferation of T cells., Proc. Natl. Acad. Sci. U.S.A.
Martin et al., 2001, Ribosomal S6 kinase 2 inhibition by a potent C-terminal repressor domain is relieved by mitogen-activated protein-extracellular signal-regulated kinase kinase-regulated phosphorylation., J. Biol. Chem.
Martin et al., 2001, Regulation of ribosomal S6 kinase 2 by effectors of the phosphoinositide 3-kinase pathway., J. Biol. Chem.
Schalm et al., 2002, Identification of a conserved motif required for mTOR signaling., Curr. Biol.
Perera et al., 2009, HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy., Proc. Natl. Acad. Sci. U.S.A.
Schaefer et al., 2007, Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin., Am. J. Pathol.
Poulalhon et al., 2006, Modulation of collagen and MMP-1 gene expression in fibroblasts by the immunosuppressive drug rapamycin. A direct role as an antifibrotic agent?, J. Biol. Chem.
Poston et al., 1999, Antisense oligodeoxynucleotides prevent acute cardiac allograft rejection via a novel, nontoxic, highly efficient transfection method., Transplantation
Ling Q et al., 2013, Association between donor and recipient TCF7L2 gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation in a Han Chinese population., J Hepatol
Kurzawski M et al., 2011, Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus., Pharmacol Rep
Maude et al., 2012, Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia., Blood
Ghosh AP et al., 2015, Point mutations of the mTOR-RHEB pathway in renal cell carcinoma., Oncotarget
Wu M et al., 2015, Flcn-deficient renal cells are tumorigenic and sensitive to mTOR suppression., Oncotarget

SIROLIMUS EIF4E

Interaction Score: 2.33

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10516161 8816458 10477262 15292274 14581487 9867830

Sources:
NCI
SIROLIMUS DCN

Interaction Score: 1.99

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17200203

Sources:
NCI
SIROLIMUS FKBP4

Interaction Score: 1.99

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
1700475

Sources:
NCI
SIROLIMUS RBL2

Interaction Score: 1.99

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
8895523

Sources:
NCI
SIROLIMUS IL7

Interaction Score: 1.99

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
14657335

Sources:
NCI
SIROLIMUS FLCN

Interaction Score: 1.0

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26418749

Sources:
CIViC
SIROLIMUS FBXW7

Interaction Score: 0.75

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
24586741 18787170 23558291

Sources:
JAX-CKB CIViC CGI
SIROLIMUS TSC1

Interaction Score: 0.66

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
19966866

Sources:
CIViC
SIROLIMUS TCF7L2

Interaction Score: 0.6

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23041303 21857094

Sources:
PharmGKB
SIROLIMUS FKBP1A

Interaction Score: 0.58

Interaction Types & Directionality:

other/unknown

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction FK506-binding protein 1A inhibitor

Details of the Assay for Interaction Measuring ability to inhibit the proteins rotamase activity

PMIDs:
12742462 24893224 24836070 11752352

Sources:
TEND DTC TdgClinicalTrial TTD DrugBank GuideToPharmacology ChemblInteractions
SIROLIMUS RHEB

Interaction Score: 0.5

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26255626

Sources:
CIViC
SIROLIMUS IL15

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
14605212

Sources:
NCI
SIROLIMUS DDC

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16126007

Sources:
NCI
SIROLIMUS WT1

Interaction Score: 0.28

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15782132

Sources:
NCI
SIROLIMUS IL10

Interaction Score: 0.23

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
12907620 22094953

Sources:
NCI PharmGKB
SIROLIMUS IGFBP1

Interaction Score: 0.22

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11942857

Sources:
NCI
SIROLIMUS EML4

Interaction Score: 0.2

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Sirolimus + X-396

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
21613408

Sources:
JAX-CKB
SIROLIMUS UGT1A8

Interaction Score: 0.18

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
20565459

Sources:
PharmGKB
SIROLIMUS POR

Interaction Score: 0.18

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23974086

Sources:
PharmGKB
SIROLIMUS RB1

Interaction Score: 0.17

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type retinoblastoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
21468343 23454836 1689463

Sources:
JAX-CKB
SIROLIMUS CTLA4

Interaction Score: 0.17

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
7982907 11698435

Sources:
NCI
SIROLIMUS MTOR

Interaction Score: 0.16

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family MTOR inhibitor

Alteration MTOR:L1460P,S2215Y,R2505P

Trial Name LCP-Siro, sirolimus

PMIDs:
26619011 19848404 24631838 12742462 20005306 27482884 27279227 17563385 24893224 24836070 11752352 19620795

Sources:
ClearityFoundationClinicalTrial DTC DoCM TdgClinicalTrial CIViC TTD DrugBank TALC MyCancerGenome CGI
SIROLIMUS APC

Interaction Score: 0.16

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
18768809 20080688

Sources:
JAX-CKB
SIROLIMUS NF1

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family MTOR inhibitor

Alteration NF1:del

Alteration NF1:.

PMIDs:
23171796

Sources:
CIViC CGI
SIROLIMUS FGF2

Interaction Score: 0.14

Interaction Types & Directionality:

other/unknown

Interaction Info:

Trial Name LCP-Siro, sirolimus

Novel drug target Established target

PMIDs:
12742462

Sources:
TdgClinicalTrial DrugBank
SIROLIMUS RPS6KB1

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11108720 11108711 11967149

Sources:
NCI
SIROLIMUS IL17A

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17061983

Sources:
NCI
SIROLIMUS STK11

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
20142330

Sources:
JAX-CKB
SIROLIMUS TGM2

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16127150

Sources:
NCI
SIROLIMUS CYP3A5

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16815317 17941052 26543771 28245187 22094953 26256674 15707415 23974086

Sources:
PharmGKB
SIROLIMUS ITGAL

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10515383

Sources:
NCI
SIROLIMUS MMP1

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16914544

Sources:
NCI
SIROLIMUS DDIT3

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11145585

Sources:
NCI
SIROLIMUS PRKAA1

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16027121

Sources:
NCI
SIROLIMUS PIK3CA

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
15647370 15878982 26882569 28514312 19029981 17376864

Sources:
NCI JAX-CKB CIViC
SIROLIMUS HRAS

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Sirolimus + Trametinib

Indication/Tumor Type head and neck squamous cell carcinoma

Response Type sensitive

PMIDs:
26882569

Sources:
JAX-CKB
SIROLIMUS EGFR

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

Alteration EGFR:P753S

Drug family EGFR mAb inhibitor;MTOR inhibitor

combination therapy Cetuximab;Sirolimus

PMIDs:
24934779 24813888 25157968 18089823

Sources:
DoCM JAX-CKB CIViC CGI
SIROLIMUS MAPK10

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15683719

Sources:
NCI
SIROLIMUS PIM1

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15642745

Sources:
NCI
SIROLIMUS BAX

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15782132

Sources:
NCI
SIROLIMUS PLAU

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11245436

Sources:
NCI
SIROLIMUS MCL1

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17010674

Sources:
NCI
SIROLIMUS NOS1

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16408196

Sources:
NCI
SIROLIMUS ABCG2

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17031644

Sources:
NCI
SIROLIMUS PGR

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
1284044

Sources:
NCI
SIROLIMUS JAK2

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22955920

Sources:
CIViC
SIROLIMUS AKT1

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type predicted – sensitive

combination therapy Doxorubicin + Sirolimus

Evidence Type Actionable

PMIDs:
18708578

Sources:
JAX-CKB
SIROLIMUS KRAS

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type conflicting

Approval Status Preclinical

PMIDs:
26144316 26882569

Sources:
JAX-CKB
SIROLIMUS FGFR1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy AZD4547 + Sirolimus

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

PMIDs:
26359452

Sources:
JAX-CKB
SIROLIMUS ABCB1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23073467 28676933 14569063

Sources:
NCI PharmGKB
SIROLIMUS NR1I2

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
28676933

Sources:
PharmGKB
SIROLIMUS ERBB2

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
19122144

Sources:
CIViC
SIROLIMUS TP53

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type conflicting

Approval Status Preclinical

PMIDs:
26144316 16651424

Sources:
NCI JAX-CKB
SIROLIMUS PTEN

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family MTOR inhibitor

Alteration PTEN:del

Alteration PTEN:.

PMIDs:
None found

Sources:
CGI
SIROLIMUS OPRK1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
SIROLIMUS NFE2L2

Interaction Score: 0.0

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17652445

Sources:
NCI
SIROLIMUS AR

Interaction Score: 0.0

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC

DrugBank: DB00877

Version: 5.1.7

Alternate Names:

SIROLIMUS DrugBank Drug Name

53123-88-9 CAS Number

Gd-sirolimus Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Groups investigational

Publications:

Sehgal, 2003, Sirolimus: its discovery, biological properties, and mechanism of action., Transplant. Proc.

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Dowling et al., 2010, Dissecting the role of mTOR: lessons from mTOR inhibitors., Biochim. Biophys. Acta

MyCancerGenome: SIROLIMUS
- Version: 20-Jun-2017
Alternate Names:

AY22989 Development Name

SILA9268A Development Name

WY-090217 Development Name

Drug Info:

Drug Class Kinase Inhibitors

Notes rapalogue

Publications:
TEND: SIROLIMUS
- Version: 01-August-2011
Alternate Names:

SIROLIMUS Primary Drug Name

Drug Info:

Year of Approval 2007

Drug Class immunosuppressive agents

Publications:
TdgClinicalTrial: SIROLIMUS
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications immunosuppressant

Drug Class Small Molecule

FDA Approval approved

Publications:

DTC: SIROLIMUS

Version: 02-September-2020

Alternate Names:

CHEMBL413 ChEMBL Drug ID

Drug Info:

Publications:

Nowak P et al., 2009, Discovery of potent and selective inhibitors of the mammalian target of rapamycin (mTOR) kinase., J Med Chem

Pratt MR et al., 2007, Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt., Proc Natl Acad Sci U S A

Du L et al., 2014, Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum., J Nat Prod

NCI: RAPAMYCIN

Version: 14-September-2017

Alternate Names:

C1212 NCI drug code

Drug Info:

Publications:

Nardacci et al., 2005, Characterization of cell death pathways in human immunodeficiency virus-associated encephalitis., Am. J. Pathol.

Purdom-Dickinson et al., 2007, Translational control of nrf2 protein in activation of antioxidant response by oxidants., Mol. Pharmacol.

Wei et al., 2006, Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance., Cancer Cell

NCI: SIROLIMUS

Version: 14-September-2017

Alternate Names:

C1212 NCI drug code

Drug Info:

Publications:

Pawarode et al., 2007, Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus and sirolimus on drug transport by multidrug resistance proteins., Cancer Chemother. Pharmacol.

Cummins et al., 2004, CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam., J. Pharmacol. Exp. Ther.

PharmGKB: sirolimus

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Woillard JB et al., 2013, Effect of CYP3A422, POR28, and PPARA rs4253728 on sirolimus in vitro metabolism and trough concentrations in kidney transplant recipients., Clin Chem

Woillard JB et al., 2010, Risk of diarrhoea in a long-term cohort of renal transplant patients given mycophenolate mofetil: the significant role of the UGT1A8 2 variant allele., Br J Clin Pharmacol

Mbatchi LC et al., 2017, Association of NR1I2, CYP3A5 and ABCB1 genetic polymorphisms with variability of temsirolimus pharmacokinetics and toxicity in patients with metastatic bladder cancer., Cancer Chemother Pharmacol

JAX-CKB: Sirolimus

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Jardim et al., 2014, FBXW7 mutations in patients with advanced cancers: clinical and molecular characteristics and outcomes with mTOR inhibitors., PLoS ONE

Mao et al., 2008, FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression., Science

Wang et al., 2013, Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells., Biochem. Biophys. Res. Commun.

DoCM: RAPAMYCIN

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.

Grabiner et al., 2014, A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity., Cancer Discov

DoCM: SIROLIMUS

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Ganesan et al., 2016, Epidermal Growth Factor Receptor P753S Mutation in Cutaneous Squamous Cell Carcinoma Responsive to Cetuximab-Based Therapy., J. Clin. Oncol.

MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn

Engelman et al., 2007, PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib., Cancer Res.

CIViC: SIROLIMUS

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Perera et al., 2009, HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy., Proc. Natl. Acad. Sci. U.S.A.

Ganesan et al., 2016, Epidermal Growth Factor Receptor P753S Mutation in Cutaneous Squamous Cell Carcinoma Responsive to Cetuximab-Based Therapy., J. Clin. Oncol.

Maertens et al., 2013, Elucidating distinct roles for NF1 in melanomagenesis., Cancer Discov

TALC: SIROLIMUS
- Version: 12-May-2016
Alternate Names:

SIROLIMUS Primary Drug Name

SIROLIMUS Drug Generic Name

RAPAMUNE Drug Trade Name

Drug Info:

Publications:
TTD: Sirolimus
- Version: 2020.06.01
Alternate Names:

D03LJR TTD Drug ID

Drug Info:

Publications:
GuideToPharmacology: 178102653
- Version: 29-September-2020
Alternate Names:

SIROLIMUS GuideToPharmacology Ligand Name

Drug Info:

Publications:
TTD: Rapamycin
- Version: 2020.06.01
Alternate Names:

D0T6DK TTD Drug ID

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL413
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL413
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: RAPAMYCIN
- Version: 30-February-2014
Alternate Names:

Drug Info:

Publications:
ClearityFoundationClinicalTrial: SIROLIMUS
- Version: 15-June-2013
Alternate Names:

Drug Info:

Publications:
CGI: Sirolimus
- Version: 27-September-2017
Alternate Names:

Drug Info:

Publications:

Indication/Tumor Type	colon cancer
Response Type	sensitive
Approval Status	Preclinical

Direct Interaction	yes
Mechanism of Interaction	FK506-binding protein 1A inhibitor
Details of the Assay for Interaction	Measuring ability to inhibit the proteins rotamase activity

combination therapy	Sirolimus + X-396
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive

Indication/Tumor Type	retinoblastoma
Response Type	sensitive
Approval Status	Preclinical

Drug family	MTOR inhibitor
Alteration	MTOR:L1460P,S2215Y,R2505P
Trial Name	LCP-Siro, sirolimus

Trial Name	LCP-Siro, sirolimus
Novel drug target	Established target

Evidence Type	Actionable
Approval Status	Preclinical
Response Type	sensitive

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Preclinical

combination therapy	Sirolimus + Trametinib
Indication/Tumor Type	head and neck squamous cell carcinoma
Response Type	sensitive

Alteration	EGFR:P753S
Drug family	EGFR mAb inhibitor;MTOR inhibitor
combination therapy	Cetuximab;Sirolimus

other/unknown
inhibitor (inhibitory)

Response Type	predicted – sensitive
combination therapy	Doxorubicin + Sirolimus
Evidence Type	Actionable

Indication/Tumor Type	pancreatic ductal adenocarcinoma
Response Type	conflicting
Approval Status	Preclinical

combination therapy	AZD4547 + Sirolimus
Indication/Tumor Type	lung adenocarcinoma
Response Type	sensitive

SIROLIMUS	DrugBank Drug Name
53123-88-9	CAS Number
Gd-sirolimus	Drug Brand

Drug Type	small molecule
Drug Groups	approved
Drug Groups	investigational

AY22989	Development Name
SILA9268A	Development Name
WY-090217	Development Name

SIROLIMUS	Primary Drug Name
SIROLIMUS	Drug Generic Name
RAPAMUNE	Drug Trade Name

SIROLIMUS Drug Record

SIROLIMUS chembl:CHEMBL413 ApprovedAntineoplasticImmunotherapy

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10516161 8816458 10477262 15292274 14581487 9867830

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 17200203

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 1700475

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 8895523

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 14657335

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 26418749

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type colon cancer Response Type sensitive Approval Status Preclinical

PMIDs: 24586741 18787170 23558291

Sources: JAX-CKB CIViC CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 19966866

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23041303 21857094

Sources: PharmGKB

Interaction Types & Directionality: other/unknown inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction FK506-binding protein 1A inhibitor Details of the Assay for Interaction Measuring ability to inhibit the proteins rotamase activity

PMIDs: 12742462 24893224 24836070 11752352

Sources: TEND DTC TdgClinicalTrial TTD DrugBank GuideToPharmacology ChemblInteractions

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 26255626

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 14605212

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 16126007

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15782132

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 12907620 22094953

Sources: NCI PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 11942857

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Sirolimus + X-396 Indication/Tumor Type non-small cell lung carcinoma Response Type sensitive

PMIDs: 21613408

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 20565459

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23974086

Interaction Types & Directionality:

n/a

PMIDs:
10516161 8816458 10477262 15292274 14581487 9867830

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
17200203

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
1700475

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
8895523

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
14657335

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
26418749

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
24586741 18787170 23558291

Sources:
JAX-CKB CIViC CGI

Interaction Types & Directionality:

n/a

PMIDs:
19966866

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
23041303 21857094

Sources:
PharmGKB

Interaction Types & Directionality:

other/unknown

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction FK506-binding protein 1A inhibitor

Details of the Assay for Interaction Measuring ability to inhibit the proteins rotamase activity

PMIDs:
12742462 24893224 24836070 11752352

Sources:
TEND DTC TdgClinicalTrial TTD DrugBank GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

n/a

PMIDs:
26255626

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
14605212

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
16126007

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
15782132

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
12907620 22094953

Sources:
NCI PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
11942857

Sources:
NCI

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Sirolimus + X-396

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
21613408

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
20565459

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
23974086

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type retinoblastoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
21468343 23454836 1689463

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
7982907 11698435

Sources:
NCI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family MTOR inhibitor

Alteration MTOR:L1460P,S2215Y,R2505P

Trial Name LCP-Siro, sirolimus

PMIDs:
26619011 19848404 24631838 12742462 20005306 27482884 27279227 17563385 24893224 24836070 11752352 19620795

Sources:
ClearityFoundationClinicalTrial DTC DoCM TdgClinicalTrial CIViC TTD DrugBank TALC MyCancerGenome CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
18768809 20080688

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family MTOR inhibitor

Alteration NF1:del

Alteration NF1:.

PMIDs:
23171796

Sources:
CIViC CGI

Interaction Types & Directionality:

other/unknown