sirolimus Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
immunosuppressants, rapamycin derivatives	2446	53123-88-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: sirolimus rapamycin rapammune rapamune supralimus rapalimus AY22989 AY-22989	A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Limited data describing efficacy in patients with COVID-19 is available. However, its efficacy and safety in the treatment of COVID-19 was not established. Molecular weight: 914.19 Formula: C51H79NO13 CLOGP: 7.04 LIPINSKI: 3 HAC: 14 HDO: 3 TPSA: 195.43 ALOGS: -5.72 ROTB: 6 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

sirolimus
rapamycin
rapammune
rapamune
supralimus
rapalimus
AY22989
AY-22989

A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Limited data describing efficacy in patients with COVID-19 is available. However, its efficacy and safety in the treatment of COVID-19 was not established.

Molecular weight: 914.19
Formula: C51H79NO13
CLOGP: 7.04
LIPINSKI: 3
HAC: 14
HDO: 3
TPSA: 195.43
ALOGS: -5.72
ROTB: 6

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
3	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	2 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.15 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	15 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
Sept. 15, 1999	FDA	PF PRISM CV

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Transplant dysfunction	2024.93	18.20	435	15017	4247	46666363
Transplant rejection	1919.14	18.20	476	14976	9120	46661490
Ovarian cyst	1403.98	18.20	403	15049	13684	46656926
Acne	1249.72	18.20	399	15053	19520	46651090
Sleep disorder due to general medical condition, insomnia type	575.28	18.20	162	15290	5087	46665523
Alopecia	552.20	18.20	444	15008	161970	46508640
Product use in unapproved indication	270.60	18.20	230	15222	90043	46580567
Liver function test abnormal	216.75	18.20	154	15298	46333	46624277
Epstein-Barr virus infection	176.62	18.20	71	15381	6713	46663897
Post transplant lymphoproliferative disorder	168.57	18.20	59	15393	3797	46666813
Kidney transplant rejection	164.78	18.20	59	15393	4059	46666551
Thrombotic microangiopathy	162.75	18.20	71	15381	8235	46662375
Product use issue	131.15	18.20	159	15293	94485	46576125
Kidney fibrosis	120.57	18.20	36	15416	1389	46669221
Condition aggravated	115.74	18.20	252	15200	244800	46425810
Immunosuppressant drug level increased	112.65	18.20	42	15410	3240	46667370
Graft versus host disease	112.02	18.20	51	15401	6537	46664073
Off label use	104.04	18.20	318	15134	379523	46291087
Pneumonia	99.28	18.20	311	15141	376009	46294601
Liver transplant rejection	95.97	18.20	30	15422	1353	46669257
Epstein-Barr virus associated lymphoproliferative disorder	89.88	18.20	29	15423	1450	46669160
Polyomavirus-associated nephropathy	77.61	18.20	26	15426	1464	46669146
Human herpesvirus 6 infection	72.13	18.20	28	15424	2411	46668199
Chronic allograft nephropathy	70.63	18.20	20	15432	638	46669972
Smooth muscle cell neoplasm	69.07	18.20	19	15433	544	46670066
Loss of personal independence in daily activities	67.87	18.20	89	15363	57094	46613516
Graft versus host disease in gastrointestinal tract	67.43	18.20	27	15425	2523	46668087
Cytomegalovirus infection	64.17	18.20	51	15401	18093	46652517
Cryptosporidiosis infection	61.94	18.20	15	15437	255	46670355
MELAS syndrome	56.48	18.20	12	15440	109	46670501
Renal graft infection	56.28	18.20	12	15440	111	46670499
BK virus infection	54.64	18.20	24	15428	2825	46667785
JC virus infection	52.43	18.20	20	15432	1642	46668968
Skin squamous cell carcinoma metastatic	51.64	18.20	8	15444	6	46670604
Alveolar proteinosis	49.56	18.20	13	15439	309	46670301
Graft versus host disease in skin	48.86	18.20	21	15431	2346	46668264
Heart transplant rejection	48.75	18.20	14	15438	470	46670140
Arthralgia	47.80	18.20	31	15421	364572	46306038
Nephropathy toxic	47.44	18.20	30	15422	7424	46663186
Blood creatinine increased	43.45	18.20	85	15367	76318	46594292
Fall	43.10	18.20	28	15424	329069	46341541
Posterior reversible encephalopathy syndrome	42.02	18.20	37	15415	15104	46655506
Incorrect route of product administration	41.45	18.20	38	15414	16345	46654265
Renal impairment	41.40	18.20	82	15370	74290	46596320
Drug level increased	41.34	18.20	40	15412	18401	46652209
Pneumonitis	41.33	18.20	49	15403	28371	46642239
Lymphocele	41.18	18.20	14	15438	824	46669786
Globulins decreased	39.53	18.20	10	15442	205	46670405
Rash	39.48	18.20	36	15416	356476	46314134
Adenovirus infection	39.14	18.20	19	15433	2811	46667799
Rheumatoid arthritis	38.21	18.20	169	15283	240046	46430564
Pancreas transplant rejection	38.16	18.20	9	15443	136	46670474
Pseudomonas infection	37.90	18.20	29	15423	9729	46660881
Neurofibrosarcoma	37.73	18.20	9	15443	143	46670467
Drug level below therapeutic	37.28	18.20	19	15433	3118	46667492
Dizziness	36.95	18.20	35	15417	340379	46330231
Complications of transplanted kidney	36.84	18.20	17	15435	2246	46668364
Fatigue	36.18	18.20	94	15358	608603	46062007
Immunosuppressant drug level decreased	35.95	18.20	13	15439	919	46669691
Somnolence	35.19	18.20	5	15447	156516	46514094
Adjusted calcium decreased	34.89	18.20	8	15444	106	46670504
Avian influenza	34.31	18.20	7	15445	51	46670559
Focal segmental glomerulosclerosis	33.98	18.20	14	15438	1407	46669203
Chronic graft versus host disease	33.83	18.20	17	15435	2708	46667902
Proteinuria	33.57	18.20	34	15418	16519	46654091
Polyomavirus viraemia	33.56	18.20	10	15442	383	46670227
Cytomegalovirus infection reactivation	33.51	18.20	14	15438	1458	46669152
Bacillary angiomatosis	31.81	18.20	7	15445	76	46670534
Bronchiolitis obliterans syndrome	31.02	18.20	7	15445	86	46670524
Drug hypersensitivity	30.22	18.20	22	15430	243803	46426807
Acute graft versus host disease	30.18	18.20	18	15434	4012	46666598
Jejunal perforation	30.17	18.20	7	15445	98	46670512
Alopecia scarring	29.73	18.20	7	15445	105	46670505
Endocarditis Q fever	29.58	18.20	5	15447	10	46670600
Hypertriglyceridaemia	29.10	18.20	20	15432	5684	46664926
Chronic graft versus host disease in skin	29.04	18.20	10	15442	612	46669998
Hepatitis E	28.93	18.20	12	15440	1227	46669383
Pain in extremity	28.75	18.20	26	15426	258654	46411956
Back pain	28.67	18.20	17	15435	210022	46460588
Trichostasis spinulosa	28.14	18.20	5	15447	15	46670595
Drug interaction	27.93	18.20	137	15315	202957	46467653
Jarisch-Herxheimer reaction	26.90	18.20	8	15444	304	46670306
Constipation	26.86	18.20	12	15440	174085	46496525
Skin graft rejection	26.83	18.20	5	15447	21	46670589
Hypoalbuminaemia	26.61	18.20	24	15428	10103	46660507
Haemodialysis	26.53	18.20	23	15429	9194	46661416
Joint swelling	26.33	18.20	11	15441	166062	46504548
Graft thrombosis	26.20	18.20	7	15445	179	46670431
Dyspnoea	25.94	18.20	86	15366	515462	46155148
Anxiety	25.87	18.20	14	15438	181943	46488667
Squamous cell carcinoma	25.53	18.20	21	15431	7815	46662795
Hypersensitivity	25.42	18.20	9	15443	150312	46520298
Product dose omission issue	25.40	18.20	12	15440	168508	46502102
Muscle spasms	25.30	18.20	5	15447	123108	46547502
Pneumocystis jirovecii pneumonia	25.04	18.20	28	15424	15220	46655390
Pruritus	25.02	18.20	26	15426	242326	46428284
Lymphopenia	24.97	18.20	28	15424	15265	46655345
Drug level fluctuating	24.87	18.20	8	15444	396	46670214
Nausea	24.51	18.20	131	15321	687323	45983287
Fibrosarcoma	24.39	18.20	4	15448	6	46670604
Hepatic fibrosis	24.07	18.20	14	15438	2981	46667629
Gait disturbance	24.05	18.20	9	15443	145254	46525356
Disseminated mycobacterium avium complex infection	23.88	18.20	5	15447	42	46670568
Feeling abnormal	23.85	18.20	6	15446	125054	46545556
Overdose	23.73	18.20	81	15371	101898	46568712
Haemolytic uraemic syndrome	23.57	18.20	13	15439	2501	46668109
Renal tubular necrosis	23.48	18.20	23	15429	10736	46659874
Morphoea	22.78	18.20	7	15445	298	46670312
Kussmaul respiration	22.47	18.20	6	15446	153	46670457
Transplant failure	22.24	18.20	10	15442	1244	46669366
Pulmonary alveolar haemorrhage	22.20	18.20	15	15437	4147	46666463
Bacterial colitis	22.19	18.20	5	15447	61	46670549
Cat scratch disease	22.04	18.20	6	15446	165	46670445
Pterygium	21.87	18.20	6	15446	170	46670440
Multiple organ dysfunction syndrome	21.84	18.20	51	15401	51659	46618951
Obliterative bronchiolitis	21.82	18.20	11	15441	1764	46668846
Q fever	21.76	18.20	5	15447	67	46670543
Chest pain	21.71	18.20	16	15436	176308	46494302
Insomnia	21.59	18.20	14	15438	164910	46505700
Enterovirus infection	21.59	18.20	8	15444	606	46670004
Rhinovirus infection	21.56	18.20	14	15438	3622	46666988
Acute graft versus host disease in skin	21.51	18.20	13	15439	2969	46667641
Interstitial lung disease	21.48	18.20	52	15400	53897	46616713
Aspergillus infection	21.48	18.20	18	15434	6872	46663738
Headache	21.26	18.20	84	15368	478268	46192342
Human herpesvirus 8 infection	21.14	18.20	6	15446	193	46670417
Respiratory failure	20.92	18.20	74	15378	94742	46575868
Salivary gland mass	20.82	18.20	5	15447	82	46670528
Viraemia	20.77	18.20	9	15443	1025	46669585
Malaise	20.49	18.20	50	15402	331182	46339428
Bacterial translocation	20.41	18.20	6	15446	219	46670391
Acute hepatitis C	20.38	18.20	5	15447	90	46670520
Septic shock	20.12	18.20	53	15399	57840	46612770
Syncope	20.03	18.20	5	15447	104798	46565812
Klebsiella infection	19.94	18.20	17	15435	6645	46663965
White matter lesion	19.92	18.20	9	15443	1132	46669478
Lung transplant rejection	19.84	18.20	8	15444	761	46669849
Thymus enlargement	19.83	18.20	5	15447	101	46670509
Pulmonary artery atresia	19.51	18.20	4	15448	30	46670580
Loss of consciousness	19.13	18.20	6	15446	108232	46562378
Renal transplant	18.77	18.20	9	15443	1296	46669314
Diabetes mellitus	18.60	18.20	47	15405	50018	46620592
Pleural effusion	18.52	18.20	65	15387	82887	46587723
Cardiac murmur functional	18.48	18.20	4	15448	40	46670570
Neonatal seizure	18.42	18.20	6	15446	309	46670301
Sinusitis	18.41	18.20	10	15442	129758	46540852
Bronchopulmonary aspergillosis	18.21	18.20	17	15435	7479	46663131

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Product use in unapproved indication	422.48	14.22	337	16001	73356	29862784
Transplant rejection	351.63	14.22	146	16192	9060	29927080
Kidney transplant rejection	306.84	14.22	125	16213	7384	29928756
Off label use	289.83	14.22	499	15839	248791	29687349
Post transplant lymphoproliferative disorder	149.69	14.22	68	16270	5238	29930902
Liver transplant rejection	126.69	14.22	47	16291	2151	29933989
Immunosuppressant drug level increased	116.25	14.22	55	16283	4647	29931493
Cytomegalovirus infection	103.72	14.22	93	16245	23581	29912559
Thrombotic microangiopathy	102.78	14.22	62	16276	8548	29927592
Adenovirus infection	102.69	14.22	49	16289	4219	29931921
Product use issue	97.88	14.22	123	16215	45893	29890247
BK virus infection	95.64	14.22	47	16291	4317	29931823
Acute graft versus host disease	85.27	14.22	48	16290	5816	29930324
Transplant failure	83.19	14.22	36	16302	2468	29933672
Nephropathy toxic	81.41	14.22	58	16280	10581	29925559
Chronic allograft nephropathy	78.63	14.22	28	16310	1138	29935002
Lymphocele	76.08	14.22	29	16309	1431	29934709
Complications of transplanted kidney	74.76	14.22	39	16299	4062	29932078
Graft versus host disease	74.60	14.22	54	16284	10096	29926044
Squamous cell carcinoma	74.13	14.22	54	16284	10196	29925944
Epstein-Barr virus infection	71.65	14.22	45	16293	6661	29929479
Blood creatinine increased	66.53	14.22	151	16187	91224	29844916
Chronic graft versus host disease	63.39	14.22	35	16303	4084	29932056
Meningitis viral	62.80	14.22	21	16317	705	29935435
Nocardiosis	60.54	14.22	32	16306	3423	29932717
Proteinuria	60.21	14.22	58	16280	16087	29920053
Cytomegalovirus viraemia	60.09	14.22	38	16300	5691	29930449
Propionibacterium infection	59.52	14.22	16	16322	248	29935892
Transplant dysfunction	53.53	14.22	26	16312	2326	29933814
Kidney fibrosis	53.41	14.22	25	16313	2060	29934080
Graft versus host disease in skin	53.37	14.22	29	16309	3278	29932862
Brain abscess	50.31	14.22	26	16312	2655	29933485
Bronchopulmonary aspergillosis	49.37	14.22	46	16292	12238	29923902
Squamous cell carcinoma of skin	46.41	14.22	39	16299	9056	29927084
Graft versus host disease in liver	45.46	14.22	18	16320	984	29935156
Impaired healing	45.15	14.22	47	16291	14293	29921847
Graft versus host disease in gastrointestinal tract	44.28	14.22	25	16313	3044	29933096
Interstitial lung disease	42.13	14.22	98	16240	60099	29876041
Heart transplant rejection	41.57	14.22	18	16320	1235	29934905
Renal impairment	41.36	14.22	120	16218	84064	29852076
Central nervous system lymphoma	40.59	14.22	16	16322	864	29935276
Diaphragmatic hernia	40.32	14.22	12	16326	273	29935867
Cow pox	39.67	14.22	8	16330	30	29936110
Pleocytosis	38.25	14.22	13	16325	459	29935681
Renal tubular atrophy	37.68	14.22	16	16322	1046	29935094
Dizziness	37.29	14.22	31	16307	194878	29741262
Herpes zoster meningoencephalitis	36.76	14.22	11	16327	255	29935885
Haemolytic uraemic syndrome	36.37	14.22	19	16319	1983	29934157
Acute graft versus host disease in skin	35.41	14.22	25	16313	4491	29931649
Constipation	35.36	14.22	9	16329	112897	29823243
Focal segmental glomerulosclerosis	35.09	14.22	18	16320	1809	29934331
Fatigue	34.21	14.22	78	16260	320595	29615545
Transitional cell carcinoma	33.60	14.22	18	16320	1977	29934163
Hepatic cancer recurrent	33.30	14.22	11	16327	355	29935785
Scedosporium infection	32.98	14.22	13	16325	702	29935438
Nephrogenic diabetes insipidus	32.72	14.22	15	16323	1178	29934962
Tularaemia	32.04	14.22	8	16330	91	29936049
Protothecosis	31.73	14.22	7	16331	44	29936096
Cytomegalovirus infection reactivation	30.37	14.22	16	16322	1699	29934441
Pharyngitis	30.18	14.22	27	16311	6815	29929325
Gastroenteritis norovirus	30.11	14.22	15	16323	1417	29934723
Human herpesvirus 8 infection	29.94	14.22	12	16326	677	29935463
Drug level decreased	29.84	14.22	25	16313	5780	29930360
Multiple organ dysfunction syndrome	29.73	14.22	89	16249	63398	29872742
Right ventricular diastolic collapse	29.13	14.22	7	16331	67	29936073
Enteritis	28.87	14.22	26	16312	6619	29929521
Anxiety	28.45	14.22	7	16331	89864	29846276
Diffuse large B-cell lymphoma	27.04	14.22	27	16311	7814	29928326
Renal tubular necrosis	26.56	14.22	37	16301	15214	29920926
Renal cancer stage I	25.91	14.22	5	16333	14	29936126
Hydronephrosis	25.72	14.22	28	16310	8955	29927185
Pneumonia cytomegaloviral	25.52	14.22	17	16321	2779	29933361
Malacoplakia	25.17	14.22	7	16331	124	29936016
Pericardial effusion	25.15	14.22	43	16295	21101	29915039
Ileal ulcer	24.90	14.22	10	16328	567	29935573
Drug effective for unapproved indication	24.56	14.22	12	16326	1087	29935053
Hypotension	24.55	14.22	45	16293	200520	29735620
Neuroendocrine carcinoma of the skin	24.29	14.22	10	16328	605	29935535
Venoocclusive disease	24.25	14.22	16	16322	2574	29933566
Normocytic anaemia	24.07	14.22	13	16325	1451	29934689
Diarrhoea haemorrhagic	23.82	14.22	22	16316	5783	29930357
Mouth ulceration	23.54	14.22	29	16309	10580	29925560
Drug interaction	23.23	14.22	187	16151	199381	29736759
Aspergillus infection	22.80	14.22	28	16310	10186	29925954
Drug level increased	22.72	14.22	38	16300	18316	29917824
Nail discolouration	22.11	14.22	10	16328	761	29935379
Smooth muscle cell neoplasm	22.03	14.22	6	16332	98	29936042
Escherichia infection	21.99	14.22	22	16316	6383	29929757
Pneumonitis	21.76	14.22	47	16291	27407	29908733
Hepatitis B	21.11	14.22	21	16317	6051	29930089
Bradycardia	20.94	14.22	5	16333	65521	29870619
Basal cell carcinoma	20.88	14.22	34	16304	16034	29920106
Varicella	20.83	14.22	12	16326	1518	29934622
Obliterative bronchiolitis	20.71	14.22	11	16327	1187	29934953
Cytomegalovirus colitis	20.60	14.22	14	16324	2365	29933775
Ureteric stenosis	20.43	14.22	11	16327	1220	29934920
Splenic neoplasm malignancy unspecified	20.28	14.22	4	16334	13	29936127
Hyperlipidaemia	20.24	14.22	31	16307	13876	29922264
Ophthalmic herpes zoster	20.23	14.22	9	16329	659	29935481
Escherichia urinary tract infection	20.18	14.22	15	16323	2917	29933223
Skin squamous cell carcinoma recurrent	20.05	14.22	4	16334	14	29936126
Scleroderma	19.66	14.22	11	16327	1316	29934824
Venoocclusive liver disease	19.61	14.22	21	16317	6592	29929548
Chronic graft versus host disease in skin	19.58	14.22	9	16329	711	29935429
Anuria	19.43	14.22	26	16312	10290	29925850
Abdominal wall abscess	19.38	14.22	8	16330	487	29935653
Plasma cell myeloma	19.36	14.22	3	16335	53459	29882681
Skin erosion	19.32	14.22	12	16326	1741	29934399
Livedo reticularis	19.16	14.22	13	16325	2191	29933949
Alternaria infection	19.08	14.22	7	16331	310	29935830
Polyomavirus-associated nephropathy	19.08	14.22	15	16323	3170	29932970
Depression	19.03	14.22	13	16325	90424	29845716
Bacterial sepsis	18.93	14.22	18	16320	4908	29931232
Insomnia	18.88	14.22	14	16324	93322	29842818
Cytomegalovirus chorioretinitis	18.74	14.22	15	16323	3253	29932887
Perinephric collection	18.71	14.22	6	16332	176	29935964
Microangiopathy	18.68	14.22	9	16329	791	29935349
Spirochaetal infection	18.58	14.22	4	16334	22	29936118
Wound dehiscence	18.45	14.22	15	16323	3326	29932814
Pulmonary toxicity	18.31	14.22	17	16321	4499	29931641
Syncope	18.14	14.22	12	16326	84891	29851249
Acute graft versus host disease in intestine	18.13	14.22	13	16325	2392	29933748
Acne	18.11	14.22	24	16314	9412	29926728
Posterior reversible encephalopathy syndrome	18.04	14.22	23	16315	8684	29927456
Pyrexia	18.01	14.22	242	16096	294247	29641893
Lactobacillus infection	17.95	14.22	5	16333	89	29936051
Candida infection	17.95	14.22	31	16307	15331	29920809
Somnolence	17.73	14.22	16	16322	96747	29839393
Immunosuppressant drug level decreased	17.47	14.22	10	16328	1249	29934891
Varicella zoster virus infection	17.41	14.22	10	16328	1258	29934882
Macroglossia	17.36	14.22	6	16332	223	29935917
Human polyomavirus infection	17.29	14.22	8	16330	642	29935498
Stem cell transplant	17.18	14.22	12	16326	2119	29934021
Drug ineffective for unapproved indication	16.90	14.22	25	16313	10855	29925285
Complications of transplanted heart	16.89	14.22	6	16332	242	29935898
Osmotic demyelination syndrome	16.88	14.22	8	16330	678	29935462
Pneumocystis jirovecii infection	16.86	14.22	10	16328	1335	29934805
Pruritus	16.81	14.22	24	16314	118180	29817960
Herpes simplex	16.56	14.22	16	16322	4448	29931692
Back pain	16.48	14.22	19	16319	102577	29833563
Pulmonary cavitation	16.44	14.22	8	16330	718	29935422
Fall	16.44	14.22	48	16290	181824	29754316
Arthralgia	16.13	14.22	31	16307	135760	29800380
Urticaria	15.88	14.22	5	16333	54601	29881539
Chronic obstructive pulmonary disease	15.80	14.22	3	16335	46123	29890017
Bladder transitional cell carcinoma	15.67	14.22	12	16326	2441	29933699
Microvillous inclusion disease	15.60	14.22	4	16334	51	29936089
Pathogen resistance	15.54	14.22	21	16317	8389	29927751
Muscle spasms	15.50	14.22	8	16330	64830	29871310
Haemorrhagic pneumonia	15.45	14.22	5	16333	151	29935989
Pyelonephritis acute	15.30	14.22	10	16328	1583	29934557
Pneumonia adenoviral	15.24	14.22	5	16333	158	29935982
Hyperhidrosis	14.99	14.22	9	16329	67081	29869059
Rabies	14.72	14.22	3	16335	12	29936128
Peritoneal hernia	14.72	14.22	3	16335	12	29936128
Ovarian cyst	14.72	14.22	3	16335	12	29936128
Pneumatosis intestinalis	14.69	14.22	12	16326	2678	29933462
Epstein-Barr viraemia	14.69	14.22	8	16330	908	29935232
Cachexia	14.55	14.22	18	16320	6593	29929547
Disease recurrence	14.53	14.22	27	16311	14134	29922006
Rhinitis	14.45	14.22	15	16323	4544	29931596
Nausea	14.36	14.22	99	16239	296858	29639282
Overdose	14.22	14.22	15	16323	84322	29851818

Pharmacologic Action:

Source	Code	Description
ATC	L04AA10	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Selective immunosuppressants
ATC	S01XA23	SENSORY ORGANS OPHTHALMOLOGICALS OTHER OPHTHALMOLOGICALS Other ophthalmologicals
FDA MoA	N0000175076	Protein Kinase Inhibitors
FDA PE	N0000175550	Decreased Immunologic Activity
FDA EPC	N0000175605	Kinase Inhibitor
FDA MoA	N0000175624	mTOR Inhibitors
FDA EPC	N0000175625	mTOR Inhibitor Immunosuppressant
MeSH PA	D000900	Anti-Bacterial Agents
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000903	Antibiotics, Antineoplastic
MeSH PA	D000935	Antifungal Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D007155	Immunologic Factors
MeSH PA	D007166	Immunosuppressive Agents
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:35705	immunosuppressant
CHEBI has role	CHEBI:36047	antibacterial drugs
CHEBI has role	CHEBI:68481	mammalian target of rapamycin inhibitor
CHEBI has role	CHEBI:149553	anti-coronaviral agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Pulmonary lymphangioleiomyomatosis	indication	277844007	DOID:3319
Renal cell carcinoma	indication	702391001	DOID:4450
Prevention of Kidney Transplant Rejection	indication
Coronavirus infection	off-label use	186747009
Prevention of Cardiac Transplant Rejection	off-label use
Hypercholesterolemia	contraindication	13644009
Hyperbilirubinemia	contraindication	14783006	DOID:2741
Transplantation of liver	contraindication	18027006
Progressive multifocal leukoencephalopathy	contraindication	22255007	DOID:643
Cytomegalovirus infection	contraindication	28944009
Proteinuria	contraindication	29738008	DOID:576
Hypertensive disorder	contraindication	38341003	DOID:10763
Infectious disease	contraindication	40733004
Body fluid retention	contraindication	43498006
Gastrointestinal perforation	contraindication	51875005
Hyperlipidemia	contraindication	55822004	DOID:1168
Acute infectious disease	contraindication	63171007
Interstitial pneumonia	contraindication	64667001
Diabetes mellitus	contraindication	73211009	DOID:9351
Hyperglycemia	contraindication	80394007	DOID:4195
Transplant of lung	contraindication	88039007
Kidney disease	contraindication	90708001	DOID:557
Secondary malignant neoplasm of cerebrum	contraindication	94248000
Malignant lymphoma	contraindication	118600007	DOID:0060058
Perioperative care	contraindication	133897009
Cerebrovascular accident	contraindication	230690007
Interstitial lung disease	contraindication	233703007	DOID:3082
Lymphedema	contraindication	234097001	DOID:4977
Disease of liver	contraindication	235856003	DOID:409
Impaired wound healing	contraindication	271618001
Peripheral edema	contraindication	271809000
Pregnancy, function	contraindication	289908002
Hypertriglyceridemia	contraindication	302870006
Primary malignant neoplasm	contraindication	372087000
Malignant neoplasm of skin	contraindication	372130007	DOID:4159
Pericardial effusion	contraindication	373945007	DOID:118
Surgical procedure	contraindication	387713003
Ascites	contraindication	389026000
Breastfeeding (mother)	contraindication	413712001
Pneumocystosis jiroveci pneumonia	contraindication	415125002	DOID:11339
Malignant neoplasm of brain	contraindication	428061005	DOID:1319
Bronchial Anastomotic Dehiscence in Lung Transplant	contraindication
BK Polyomavirus Reactivation Nephropathy	contraindication
Sirolimus Toxicity	contraindication
Hepatic Artery Thrombosis in Liver Transplant	contraindication
Pleural Effusions	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.5	acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
1MG/ML	RAPAMUNE	PF PRISM CV	N021083	Sept. 15, 1999	RX	SOLUTION	ORAL	May 28, 2022	TREATMENT OF LYMPHANGIOLEIOMYOMATOSIS (LAM)
0.5MG	RAPAMUNE	PF PRISM CV	N021110	Jan. 25, 2010	RX	TABLET	ORAL	May 28, 2022	TREATMENT OF LYMPHANGIOLEIOMYOMATOSIS (LAM)
1MG	RAPAMUNE	PF PRISM CV	N021110	Aug. 25, 2000	RX	TABLET	ORAL	May 28, 2022	TREATMENT OF LYMPHANGIOLEIOMYOMATOSIS (LAM)
2MG	RAPAMUNE	PF PRISM CV	N021110	Aug. 22, 2002	RX	TABLET	ORAL	May 28, 2022	TREATMENT OF LYMPHANGIOLEIOMYOMATOSIS (LAM)
5MG Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons	RAPAMUNE	PF PRISM CV	N021110	Feb. 23, 2004	DISCN	TABLET	ORAL	May 28, 2022	TREATMENT OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Peptidyl-prolyl cis-trans isomerase FKBP1A	Enzyme	P62942	FKB1A_HUMAN	INHIBITOR	Kd	8.96	WOMBAT-PK	CHEMBL
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	5.70	DRUG MATRIX
Cytochrome P450 2C9	Enzyme	P11712	CP2C9_HUMAN		IC50	5.70	DRUG MATRIX
Cytochrome P450 2C19	Enzyme	P33261	CP2CJ_HUMAN		IC50	5.40	DRUG MATRIX
Sodium/nucleoside cotransporter 1	Transporter	O00337	S28A1_HUMAN		Ki	6.43	DRUG MATRIX
Peptidyl-prolyl cis-trans isomerase FKBP3	Enzyme	Q00688	FKBP3_HUMAN		Kd	9.70	WOMBAT-PK
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		IC50	6.20	WOMBAT-PK
Serine/threonine-protein kinase mTOR	Kinase	P42345	MTOR_HUMAN		IC50	10	CHEMBL
Eukaryotic translation initiation factor 4E	Nuclear other	P06730	IF4E_HUMAN		Kd	9.30	CHEMBL
Programmed cell death protein 4	Unclassified	Q53EL6	PDCD4_HUMAN		EC50	7.30	CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP5	Enzyme	Q13451	FKBP5_HUMAN		Ki	8.52	CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP1B	Enzyme	P68106	FKB1B_HUMAN		Kd	9.70	CHEMBL

External reference:

ID	Source
4021176	VUID
N0000148624	NUI
D00753	KEGG_DRUG
4021176	VANDF
C0878382	UMLSCUI
CHEBI:9168	CHEBI
CHEMBL413	ChEMBL_ID
5284616	PUBCHEM_CID
D020123	MESH_DESCRIPTOR_UI
DB00877	DRUGBANK_ID
6031	IUPHAR_LIGAND_ID
7104	INN_ID
W36ZG6FT64	UNII
258355	RXNORM
210889	MMSL
31418	MMSL
8303	MMSL
d04453	MMSL
007885	NDDF
116109004	SNOMEDCT_US
387014003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1030	SOLUTION	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1040	TABLET, SUGAR COATED	0.50 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1041	TABLET, SUGAR COATED	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1042	TABLET, SUGAR COATED	2 mg	ORAL	NDA	34 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	50268-718	TABLET	1 mg	ORAL	ANDA	29 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	55111-653	TABLET	1 mg	ORAL	ANDA	28 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	55111-654	TABLET	2 mg	ORAL	ANDA	28 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	59762-1001	TABLET, SUGAR COATED	0.50 mg	ORAL	NDA AUTHORIZED GENERIC	31 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	59762-1002	TABLET, SUGAR COATED	1 mg	ORAL	NDA AUTHORIZED GENERIC	31 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	59762-1003	TABLET, SUGAR COATED	2 mg	ORAL	NDA AUTHORIZED GENERIC	31 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	59762-1205	SOLUTION	1 mg	ORAL	NDA AUTHORIZED GENERIC	34 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	60505-6197	SOLUTION	1 mg	ORAL	ANDA	31 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	65841-771	TABLET, FILM COATED	0.50 mg	ORAL	ANDA	1 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	66689-347	SOLUTION	1 mg	ORAL	ANDA	29 sections
Sirolimus	Human Prescription Drug Label	1	67877-746	TABLET	0.50 mg	ORAL	ANDA	29 sections
Sirolimus	Human Prescription Drug Label	1	67877-747	TABLET	1 mg	ORAL	ANDA	29 sections
Sirolimus	Human Prescription Drug Label	1	67877-748	TABLET	2 mg	ORAL	ANDA	29 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	68084-915	TABLET	1 mg	ORAL	ANDA	30 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	68382-520	TABLET, FILM COATED	0.50 mg	ORAL	ANDA	27 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	68462-682	TABLET, FILM COATED	0.50 mg	ORAL	ANDA	29 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	68462-683	TABLET, FILM COATED	1 mg	ORAL	ANDA	29 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	68462-684	TABLET, FILM COATED	2 mg	ORAL	ANDA	29 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	69238-1594	SOLUTION	1 mg	ORAL	ANDA	30 sections