RAP

RAPAMYCIN IMMUNOSUPPRESSANT DRUG

Created:	1999-07-08
Last modified:	2011-06-04

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24 entries where RAP is found as a standalone ligand

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Chemical Details
Formal Charge	0
Atom Count	144
Chiral Atom Count	15
Bond Count	147
Aromatic Bond Count	0

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Chemical Component Summary
Name	RAPAMYCIN IMMUNOSUPPRESSANT DRUG
Systematic Name (OpenEye OEToolkits)	n/a
Formula	C₅₁ H₇₉ N O₁₃
Molecular Weight	914.172
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	ACDLabs	10.04	O=C2C(C)CC(C=CC=CC=C(C)C(OC)CC4OC(O)(C(=O)C(=O)N3C(C(=O)OC(C(C)CC1CCC(O)C(OC)C1)CC(=O)C(C=C(C)C(O)C2OC)C)CCCC3)C(CC4)C)C
SMILES	CACTVS	3.341	CO[CH]1C[CH](CC[CH]1O)C[CH](C)[CH]2CC(=O)[CH](C)C=C(C)[CH](O)[CH](OC)C(=O)[CH](C)C[CH](C)C=CC=CC=C(C)[CH](C[CH]3CC[CH](C)[C](O)(O3)C(=O)C(=O)N4CCCC[CH]4C(=O)O2)OC
SMILES	OpenEye OEToolkits	1.5.0	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
Canonical SMILES	CACTVS	3.341	CO[C@@H]1C[C@@H](CC[C@H]1O)C[C@@H](C)[C@@H]2CC(=O)[C@H](C)/C=C(C)/[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)/C=C/C=C/C=C(C)/[C@H](C[C@@H]3CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N4CCCC[C@H]4C(=O)O2)OC
Canonical SMILES	OpenEye OEToolkits	1.5.0	C[C@@H]1CC[C@H]2C[C@@H](C(=CC=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)O)C)/C)O)OC)C)C)C)OC
InChI	InChI	1.03	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	InChI	1.03	QFJCIRLUMZQUOT-HPLJOQBZSA-N

Drug Info: DrugBank

DrugBank ID	DB00877
Name	Sirolimus
Groups	approved investigational
Description	Sirolimus, also known as rapamycin, is a macrocyclic lactone antibiotic produced by bacteria _Streptomyces hygroscopicus_, which was isolated from the soil of the Vai Atari region of Rapa Nui (Easter Island).[A242412] It was first isolated and identified as an antifungal agent with potent anticandida activity; however, after its potent antitumor and immunosuppressive activities were later discovered, it was extensively investigated as an immunosuppressive and antitumour agent.[A13448] Its primary mechanism of action is the inhibition of the mammalian target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that regulates cell growth, proliferation, and survival. mTOR is an important therapeutic target for various diseases, as it was shown to regulate longevity and maintain normal glucose homeostasis.[A242417] Targeting mTOR received more attention especially in cancer, as mTOR signalling pathways are constitutively activated in many types of human cancer.[A1320] Sirolimus was first approved by the FDA in 1999 for the prophylaxis of organ rejection in patients aged 13 years and older receiving renal transplants.[A242372] In November 2000, the drug was recognized by the European Agency as an alternative to calcineurin antagonists for maintenance therapy with corticosteroids.[A242412] In May 2015, the FDA approved sirolimus for the treatment of patients with lymphangioleiomyomatosis.[L39292] In November 2021, albumin-bound sirolimus for intravenous injection was approved by the FDA for the treatment of adults with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa).[L39267] Sirolimus was also investigated in other cancers such as skin cancer, Kaposi’s Sarcoma, cutaneous T-cell lymphomas, and tuberous sclerosis.[A242372] The topical formulation of sirolimus, marketed as HYFTOR, was approved by the FDA in April 2022: this marks the first topical treatment approved in the US for facial angiofibroma associated with tuberous sclerosis complex.[L41494]
Synonyms	(-)-Rapamycin Sirolimusum Rapamycin Sirolimus Sirolimús
Brand Names	Rapamune Sirolimus Fyarro Gd-sirolimus Hyftor
Indication	Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. In patients at low-to moderate-immunologic risk, it is recommended that sirolimus be used initially in a regimen with [cyclosporine] and corticosteroids; cyclosporine should be withdrawn two to four months after transplantation. In patients at high-immunologic risk (defined as Black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [PRA; peak PRA level > 80%]), it is recommended that sirolimus be used in combination with cyclosporine and corticosteroids for the first year following transplantation.[L19809] It is also used to treat lymphangioleiomyomatosis.[L19809] In the US, albumin-bound sirolimus for intravenous injection is indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa).[L39267] In Europe, it is recommended that sirolimus for the prophylaxis of organ rejection in renal transplants is used in combination with cyclosporin microemulsion and corticosteroids for two to three months. Sirolimus may be continued as maintenance therapy with corticosteroids only if cyclosporin microemulsion can be progressively discontinued.[L7021] Topical sirolimus is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients six years of age and older.[L41489]
Categories	Agents causing angioedema Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Antineoplastic and Immunomodulating Agents Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index Cytochrome P-450 CYP3A5 Substrates Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index Cytochrome P-450 CYP3A7 Substrates Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index Cytochrome P-450 Substrates Decreased Immunologic Activity Hyperglycemia-Associated Agents Immunologic Factors Immunosuppressive Agents Immunotherapy Kinase Inhibitor Lactones Macrolides Mammalian target of rapamycin (mTOR) kinase inhibitors mTOR Inhibitor Immunosuppressant mTOR Inhibitors Myelosuppressive Agents Narrow Therapeutic Index Drugs OATP1B1/SLCO1B1 Inhibitors Ophthalmologicals P-glycoprotein inducers P-glycoprotein inhibitors P-glycoprotein substrates P-glycoprotein substrates with a Narrow Therapeutic Index Polyketides Protein Kinase Inhibitors Selective Immunosuppressants Sensory Organs Sirolimus and Prodrugs
ATC-Code	L01EG04 S01XA23 L04AA10
CAS number	53123-88-9

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Serine/threonine-protein kinase mTOR	MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTM...	unknown	inhibitor
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate
Cytochrome P450 3A5	MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNV...	unknown	substrate
Cytochrome P450 3A7	MDLIPNLAVETWLLLAVSLILLYLYGTRTHGLFKKLGIPGPTPLPFLGNA...	unknown	substrate
Serum albumin	MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIA...	unknown	binder
Alpha-1-acid glycoprotein 1	MALSWVLTVLSLLPLLEAQIPLCANLVPVPITNATLDQITGKWFYIASAF...	unknown	binder
Apolipoproteins	MKAAVLTLAVLFLTGSQARHFWQQDEPPQSPWDRVKDLATVYVDVLKDSG...	unknown	binder
P-glycoprotein 1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	unknown	substrate,inhibitor,inducer
Solute carrier organic anion transporter family member 1B1	MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKS...	unknown	inhibitor
Multidrug and toxin extrusion protein 1	MEAPEEPAPVRGGPEATLEVRGSRCLRLSAFREELRALLVLAGPAFLVQL...	unknown
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Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682