Compound Detail

CHEMBL413

SIROLIMUS

💊 Approved Drug

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💊 Approved Drug

CO[C@H]1C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N2CCCC[C@H]2C(=O)O[C@H]([C@H](C)C[C@@H]2CC[C@@H](O)[C@H](OC)C2)CC(=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/1C

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL413
Name	SIROLIMUS
Phase	Approved
Structure Type	MOL
InChI Key	QFJCIRLUMZQUOT-HPLJOQBZSA-N
Therapeutic	✓ Yes

Known Names

(-)-rapamycin AY-22989 Fyarro Hyftor L04AA10 Npc-12g NSC-226080 Rapalimus Rapamune Rapamycin Sirolimus Sirolimus component of nab-rapamycin rapamycin +2 more

393

Targets

476

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

914.2

MW (Da)

6.18

ALogP

HBA

HBD

195.4

PSA (Å²)

0.16

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	1999
Availability	Prescription
Chirality	Single Enantiomer

Routes of Administration

Oral Parenteral Topical

Flags

Black Box Warning Natural Product Chemical Probe

USAN Stem	-imus
USAN Year	1993

Extended Properties

Molecular Formula	C51H79NO13
MW	914.19
Aromatic Rings	0
Heavy Atoms	65
NP-Likeness	1.94

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
FK506-binding protein 1A inhibitor	INHIBITOR	Peptidyl-prolyl cis-trans isomerase FKBP1A	✓	✓

Indications

Angiofibroma Delayed Graft Function Eye Diseases Kidney Transplantation Neoplasms Neoplasms Tuberous Sclerosis Tuberous Sclerosis Birt-Hogg-Dube Syndrome Breast Neoplasms Carcinoma, Hepatocellular Cardiovascular Abnormalities Diabetes Mellitus, Type 1 Diabetic Nephropathies Fibroma Graft vs Host Disease Graft vs Host Disease Hodgkin Disease Influenza, Human Kidney Failure, Chronic

ATC Classification

L01EG04

sirolimus

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

L04AH01

sirolimus

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: IMMUNOSUPPRESSANTS

S01XA23

sirolimus

Level 1: SENSORY ORGANS

Level 2: OPHTHALMOLOGICALS

Drug Warnings

Black Box Warning

carcinogenicity

Country: United States

Black Box Warning

immune system toxicity

Country: United States

Black Box Warning

infectious disease

Country: United States

Black Box Warning

cardiotoxicity

Country: United States

Activity Summary

IC50 444 meas. best 10.94

Kd 13 meas. best 9.89

EC50 10 meas. best 10.0

Ki 9 meas. best 9.7

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
SF-539 CHEMBL614860	IC50	10.94	10.94	0.0	1
ES4 CHEMBL2366118	IC50	10.67	10.67	0.0	1
Serine/threonine-protein kinase mTOR CHEMBL1255165	IC50	10.3	10.3	0.1	1
Serine/threonine-protein kinase mTOR CHEMBL2842	IC50	10.3	8.475	0.1	16
mTORC1 CHEMBL4296661	IC50	10.3	8.9567	0.1	3
Human immunodeficiency virus 1 CHEMBL378	EC50	10.0	9.41	0.1	5
RL95-2 CHEMBL2366168	IC50	9.97	9.97	0.1	1
Peptidyl-prolyl cis-trans isomerase FKBP1A CHEMBL1902	Kd	9.89	9.17	0.1	3
Peptidyl-prolyl cis-trans isomerase FKBP1A CHEMBL1902	Ki	9.7	9.0633	0.2	3
Peptidyl-prolyl cis-trans isomerase FKBP1B CHEMBL2430	Kd	9.7	9.46	0.2	2
Unchecked CHEMBL612545	Kd	9.7	9.53	0.2	2
LC-2-ad CHEMBL2366260	IC50	9.37	9.37	0.4	1
Daudi CHEMBL614281	IC50	9.36	9.36	0.4	1
Peptidyl-prolyl cis-trans isomerase FKBP1A CHEMBL1902	IC50	9.35	8.805	0.5	6
NTERA-2-cl-D1 CHEMBL614206	IC50	9.35	9.35	0.4	1
Homo sapiens CHEMBL372	IC50	9.3	9.0667	0.5	3
Eukaryotic translation initiation factor 4E CHEMBL4848	Kd	9.3	9.3	0.5	1
Unchecked CHEMBL612545	Ki	9.3	7.6825	0.5	4
Serine/threonine-protein kinase mTOR CHEMBL2842	Kd	9.22	9.22	0.6	1
OS-RC-2 CHEMBL2366188	IC50	9.19	9.19	0.7	1
VA-ES-BJ CHEMBL2366259	IC50	9.14	9.14	0.7	1
GR-ST CHEMBL2366111	IC50	9.07	9.07	0.8	1
SW872 CHEMBL2366302	IC50	9.07	9.07	0.8	1
NOS-1 CHEMBL2366141	IC50	9.06	9.06	0.9	1
MC116 CHEMBL2366256	IC50	9.01	9.01	1.0	1
NCI-H1355 CHEMBL2366227	IC50	9.0	9.0	1.0	1
Mus musculus CHEMBL375	IC50	9.0	8.76	1.0	2
Peptidyl-prolyl cis-trans isomerase FKBP1A CHEMBL4295736	IC50	9.0	9.0	1.0	1
Unchecked CHEMBL612545	IC50	9.0	6.8406	1.0	18
RPMI-8226 CHEMBL614882	IC50	8.92	8.92	1.2	1
TE-15 CHEMBL2366086	IC50	8.87	8.87	1.4	1
Ramos-2G6-4C10 CHEMBL2366170	IC50	8.84	8.84	1.5	1
T-cell CHEMBL614309	IC50	8.8	7.4633	1.6	3
KU812 cell line CHEMBL613997	IC50	8.7	8.7	2.0	1
EW-1 CHEMBL2366364	IC50	8.66	8.66	2.2	1
KS-1 CHEMBL2366228	IC50	8.61	8.61	2.5	1
SK-LMS-1 CHEMBL2366096	IC50	8.6	8.6	2.5	1
TGBC1TKB CHEMBL2366089	IC50	8.57	8.57	2.7	1
TE-6 CHEMBL2366144	IC50	8.56	8.56	2.8	1
ETK-1 CHEMBL2366116	IC50	8.55	8.55	2.8	1
BE-13 CHEMBL2366303	IC50	8.53	8.53	3.0	1
Peptidyl-prolyl cis-trans isomerase FKBP5 CHEMBL2052031	Ki	8.52	8.52	3.0	1
A3-KAW CHEMBL2366273	IC50	8.52	8.52	3.0	1
TE-10 CHEMBL2366308	IC50	8.48	8.48	3.3	1
DOHH-2 CHEMBL2366181	IC50	8.47	8.47	3.4	1
ES6 CHEMBL2366373	IC50	8.46	8.46	3.4	1
Peptidyl-prolyl cis-trans isomerase FKBP5 CHEMBL2052031	Kd	8.43	8.25	3.7	2
OPM-2 CHEMBL2366353	IC50	8.38	8.38	4.2	1
Peptidyl-prolyl cis-trans isomerase FKBP4 CHEMBL4050	Kd	8.38	8.15	4.2	2
NB13 CHEMBL2366225	IC50	8.36	8.36	4.4	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	559.0	ng.hr.mL-1	Rattus norvegicus
AUC	237.6	-	Chlorocebus sabaeus
CL	50.12	uL.min-1.(10^6cells)-1	Homo sapiens
CL	150.0	uL.min-1.(10^6cells)-1	Rattus norvegicus
Cmax	55.57	nM	Rattus norvegicus
F	43.2	%	Rattus norvegicus
F	14.0	%	Homo sapiens
F	14.0	%	Homo sapiens
T1/2	13.0	hr	-
T1/2	33.4	hr	Rattus norvegicus
T1/2	63.0	hr	Homo sapiens
T1/2	62.0	hr	Homo sapiens
T1/2	14.0	hr	Rattus norvegicus
T1/2	33.4	hr	Rattus norvegicus
T1/2	40.0	hr	Homo sapiens
Tmax	0.5	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
SF-539	IC50	=	0.0116	nM	10.94	SANGER: Inhibition of human SF539 cell growth in a cell viability assay.	-
ES4	IC50	=	0.02146	nM	10.67	SANGER: Inhibition of human ES4 cell growth in a cell viability assay.	-
Serine/threonine-protein kinase mTOR	IC50	=	0.05	nM	10.3	Inhibition of mTOR (unknown origin) by lanthascreen kinase assay	38295689
Serine/threonine-protein kinase mTOR	IC50	=	0.05	nM	10.3	Inhibition of mTOR in mouse TSC1-/- MEF cells assessed as inhibition of S6 Ser24...	31223435
mTORC1	IC50	=	0.05	nM	10.3	Inhibition of mTORC1 (unknown origin)	35688004
mTORC1	IC50	=	0.06	nM	10.22	Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K p...	36533617
Human immunodeficiency virus 1	EC50	=	0.1	nM	10.0	Antiviral activity against HIV1 R5 assessed as inhibition of cell-cell fusion be...	17485501
Serine/threonine-protein kinase mTOR	IC50	=	0.1	nM	10.0	Inhibition of mTOR (unknown origin)	37669595
Serine/threonine-protein kinase mTOR	IC50	=	0.1	nM	10.0	Inhibition of human mTOR	32416459
Serine/threonine-protein kinase mTOR	IC50	=	0.1	nM	10.0	Inhibition of mTOR in HEK293 cells	32324396
Serine/threonine-protein kinase mTOR	IC50	=	0.1	nM	10.0	Inhibition of mTOR kinase expressed in human HEK293 cells by Western blot analys...	17350953
RL95-2	IC50	=	0.1073	nM	9.97	SANGER: Inhibition of human RL95-2 cell growth in a cell viability assay.	-
Peptidyl-prolyl cis-trans isomerase FKBP1A	Kd	=	0.13	nM	9.89	Binding affinity to human FKBP12 expressed in Escherichia coli BL21 DE3 Gold ass...	38582133
Human immunodeficiency virus 1	EC50	=	0.15	nM	9.82	Antiviral activity against HIV1 ADA in human PBMC assessed as reduction of p24 a...	17485501
Human immunodeficiency virus 1	EC50	=	0.18	nM	9.74	Antiviral activity against HIV1 R5 in human PBMC assessed as fractional inhibiti...	17485501
Unchecked	Kd	=	0.2	nM	9.7	Inhibition of human FKBP12 assessed as dissociation constant by Western blot ana...	37438908
Peptidyl-prolyl cis-trans isomerase FKBP1A	Kd	=	0.2	nM	9.7	Binding affinity to FKBP12 (unknown origin) assessed as dissociation constant	37984298
Peptidyl-prolyl cis-trans isomerase FKBP1A	Ki	=	0.2	nM	9.7	Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase...	9857082
Peptidyl-prolyl cis-trans isomerase FKBP1B	Kd	=	0.2	nM	9.7	Binding affinity to FKBP12 (unknown origin) by NMR analysis	24913411
LC-2-ad	IC50	=	0.4227	nM	9.37	SANGER: Inhibition of human LC-2-ad cell growth in a cell viability assay.	-

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL3885881	Rattus norvegicus	455
16415861	10.1038/nchembio762	Molecular identity unknown	265
-	10.1101/2024.03.28.586928	ADMET	100
20086156	10.1128/aac.01015-09	Mus musculus	21
20086156	10.1128/aac.01015-09	PBMC	15
22194678	10.1371/journal.pcbi.1002310	Hepatotoxicity	14
-	10.6019/CHEMBL5303304	Fibroblast	13
18024584	10.1073/pnas.0709695104	H4	13
17485501	10.1128/aac.01602-06	Human immunodeficiency virus 1	13
17128262	10.1038/nchembio832	Unchecked	12
21363918	10.1158/0008-5472.can-10-3126	Pancreatic islet cell carcinoma	11
-	10.6019/CHEMBL5303304	HEK-293T	10
16415861	10.1038/nchembio762	Saccharomyces cerevisiae	10
10888319	10.1016/s0960-894x(00)00184-0	Candida albicans	10
30629434	10.1021/acs.jmedchem.8b01825	MV4-11	9
26254279	10.18632/oncotarget.4214	Unchecked	9
26254279	10.18632/oncotarget.4214	Serine/threonine-protein kinase mTOR	9
30629434	10.1021/acs.jmedchem.8b01825	MM1.S	9
33246109	10.1016/j.bmcl.2020.127715	Unchecked	9
21363918	10.1158/0008-5472.can-10-3126	Unchecked	8

Data from ChEMBL 36 via Core Engine