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Compound Detail

CHEMBL269732

TACROLIMUS ANHYDROUS
💊 Approved Drug
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💊 Approved Drug
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC

Basic Information

ChEMBL ID CHEMBL269732
Name TACROLIMUS ANHYDROUS
Phase Approved
Structure Type MOL
InChI Key QJJXYPPXXYFBGM-LFZNUXCKSA-N
Therapeutic ✓ Yes

Known Names

104987-11-3 Anhydrous tacrolimus Fujimycin Prograph Tacro Tacrolimus anhydrous Tacrolimus, anhydrous Tsukubaenolide
25
Targets
78
Activities
4
Assay Types
26
PK Parameters
20
Publications
8
Known Names
20
Indications

Molecular Properties

804.0
MW (Da)
4.64
ALogP
12
HBA
3
HBD
178.4
PSA (Ų)
0.18
QED
2
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1994
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral Parenteral Topical

Flags

Black Box Warning Natural Product Chemical Probe
USAN Stem -imus
USAN Year 1992

Extended Properties

Molecular Formula C44H69NO12
MW 804.03
Aromatic Rings 0
Heavy Atoms 57
NP-Likeness 1.42

Indications

Arthritis, Rheumatoid Bronchiolitis Obliterans Carcinoma, Hepatocellular Colitis, Ulcerative Dermatitis, Atopic Dermatitis, Seborrheic Diabetes Mellitus, Type 1 Glomerulonephritis, Membranous Graft vs Host Disease Graft vs Host Disease Heart Diseases Hodgkin Disease Infertility Kidney Diseases Kidney Failure, Chronic Lupus Nephritis Lymphoma, Non-Hodgkin Medication Adherence Myasthenia Gravis Nephrotic Syndrome

Activity Summary

IC50 53 meas. best 10.47
Kd 12 meas. best 9.7
Ki 11 meas. best 9.4
EC50 2 meas. best 9.05

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
CD4+ve Th
CHEMBL613544
IC50 10.47 10.47 0.0 1
Unchecked
CHEMBL612545
IC50 10.25 8.76 0.1 12
ADMET
CHEMBL612558
IC50 10.22 10.06 0.1 3
T-cell
CHEMBL614309
IC50 9.74 9.4075 0.2 4
Mus musculus
CHEMBL375
IC50 9.7 9.62 0.2 2
Peptidyl-prolyl cis-trans isomerase FKBP1A
CHEMBL1902
Kd 9.7 9.625 0.2 4
Homo sapiens
CHEMBL372
IC50 9.64 9.4633 0.2 3
RBL-2H3
CHEMBL614632
IC50 9.6 9.6 0.2 3
PBMC
CHEMBL613107
IC50 9.54 9.54 0.3 1
Unchecked
CHEMBL612545
Kd 9.4 9.4 0.4 1
Peptidyl-prolyl cis-trans isomerase FKBP1A
CHEMBL1902
Ki 9.4 9.085 0.4 2
Peptidyl-prolyl cis-trans isomerase FKBP1B
CHEMBL2430
Kd 9.4 9.115 0.4 2
Peptidyl-prolyl cis-trans isomerase FKBP1A
CHEMBL1902
EC50 9.05 9.05 0.9 1
Serine/threonine-protein kinase mTOR
CHEMBL2842
IC50 9.02 8.76 0.9 2
Peptidyl-prolyl cis-trans isomerase FKBP1A
CHEMBL1902
IC50 8.64 7.102 2.3 5
Splicing factor 3B subunit 3
CHEMBL1250378
IC50 7.96 7.91 10.9 2
Protein phosphatase 3 catalytic subunit alpha
CHEMBL4445
IC50 7.83 7.83 14.8 1
Protein phosphatase 3 catalytic subunit alpha
CHEMBL4445
Kd 7.7 7.7 20.0 1
Peptidyl-prolyl cis-trans isomerase FKBP4
CHEMBL4050
Kd 7.64 7.235 23.0 2
Unchecked
CHEMBL612545
Ki 7.48 7.47 33.0 2
Peptidyl-prolyl cis-trans isomerase FKBP5
CHEMBL2052031
Kd 7.12 7.05 75.9 2
Peptidyl-prolyl cis-trans isomerase FKBP5
CHEMBL2052031
Ki 7.1 7.0767 79.0 3
Cytochrome P450 3A4
CHEMBL340
IC50 6.92 6.3767 120.0 3
Cytochrome P450 3A5
CHEMBL3019
IC50 6.85 6.525 140.0 2
Cytochrome P450 3A
CHEMBL2364675
Ki 6.44 6.325 360.0 2
Jurkat
CHEMBL397
IC50 6.44 5.84 360.0 2
Cytochrome P450 3A
CHEMBL2364675
IC50 6.13 6.08 740.0 2
Plasmodium falciparum
CHEMBL364
IC50 5.72 5.72 1900.0 1
Cytochrome P450 3A4
CHEMBL340
Ki 5.58 5.58 2660.0 1
Cytochrome P450 3A5
CHEMBL3019
Ki 5.57 5.57 2690.0 1
Broad substrate specificity ATP-binding cassette transporter ABCG2
CHEMBL5393
IC50 5.48 5.48 3300.0 1
Solute carrier organic anion transporter family member 1B1
CHEMBL1697668
IC50 5.43 5.43 3700.0 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
EC50 5.3 5.3 5000.0 1
Bile salt export pump
CHEMBL6020
IC50 5.14 5.14 7180.0 1
ATP-binding cassette sub-family C member 2
CHEMBL5748
IC50 4.39 4.39 40300.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1617.0 ng.hr.mL-1 Mus musculus
AUC 202.62 ng.hr.mL-1 Homo sapiens
AUC 2490.0 ng.hr.mL-1 Rattus norvegicus
CL 0.7 mL.min-1.kg-1 Homo sapiens
CL 0.7 mL.min-1.kg-1 Homo sapiens
CL 0.7 mL.min-1.kg-1 Homo sapiens
CL 0.7 mL.min-1.kg-1 Homo sapiens
CL 0.018 mL.min-1.g-1 Homo sapiens
CL 0.014 mL.min-1.g-1 Homo sapiens
CL 0.018 mL.min-1.g-1 Homo sapiens
CL 0.03 mL.min-1.g-1 Homo sapiens
CL 0.001 mL.min-1.g-1 Homo sapiens
CL 29.5 mL.min-1.kg-1 Mus musculus
CL 306.0 mL.min-1.g-1 Mus musculus
Cmax 29.85 nM Rattus norvegicus
F 17.0 % Homo sapiens
F 15.0 % Homo sapiens
Fu 0.01 - Homo sapiens
Fu 0.01 - Homo sapiens
MRT 27.0 hr Homo sapiens
T1/2 1.0 hr Homo sapiens
T1/2 26.0 hr Homo sapiens
T1/2 0.3683 hr Mus musculus
T1/2 0.04 hr Homo sapiens
T1/2 0.952 hr Mus musculus
Tmax 1.0 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
CD4+ve Th IC50 = 0.034 nM 10.47 Immunosuppressive activity in C57BL/6J mouse CD4+ve T cells assessed as inhibiti... 33534559
Unchecked IC50 = 0.056 nM 10.25 Inhibition of calcineurin in human Jurkat cells assessed as inhibition of NFAT-m... -
ADMET IC50 = 0.06 nM 10.22 Inhibitory activity against IL-5 production (Anti-CD3 monoclonal antibody stimul... 15369399
ADMET IC50 = 0.06 nM 10.22 Inhibitory activity against IFN-gamma production (Anti-CD3 monoclonal antibody s... 15369399
T-cell IC50 = 0.18 nM 9.74 Agonistic activity in a murine splenic T-cell proliferation assay was calculated... -
ADMET IC50 = 0.18 nM 9.74 Inhibitory activity against PPD-induced proliferation of human peripheral blood ... 15369399
Unchecked IC50 = 0.19 nM 9.72 Inhibitory activity against IL-2 receptor in human T-cell jurkat cell line stimu... 15369399
Peptidyl-prolyl cis-trans isomerase FKBP1A Kd = 0.2 nM 9.7 Binding affinity to FK506 binding protein 12 was determined -
Mus musculus IC50 = 0.2 nM 9.7 The compound was tested for its inhibitory activity against T-cell proliferation... 10450987
Peptidyl-prolyl cis-trans isomerase FKBP1A Kd = 0.2 nM 9.7 The compound was evaluated for its affinity to the binding domain of immunophili... -
Peptidyl-prolyl cis-trans isomerase FKBP1A Kd = 0.2 nM 9.7 Binding affinity to human FKBP12 expressed in Escherichia coli BL21 DE3 Gold ass... 38582133
Homo sapiens IC50 = 0.23 nM 9.64 Immunosuppressive activity examined in an in vitro model of allogenic T-lymphocy... 10543889
RBL-2H3 IC50 = 0.25 nM 9.6 Antiinflammatory activity in rat RBL2H3 cells assessed as inhibition of DNP-BSA-... 22410084
RBL-2H3 IC50 = 0.25 nM 9.6 Inhibition of TNF-alpha production in rat RBL2H3 cells after 16 hrs by ELISA 23791076
RBL-2H3 IC50 = 0.25 nM 9.6 Inhibition of DNP7-BSA antigen-induced TNFalpha release in rat RBL-2H3 cells 16901696
Mus musculus IC50 = 0.29 nM 9.54 In vitro immunosuppressive activity against proliferation of antigen stimulated ... -
PBMC IC50 = 0.29 nM 9.54 Inhibitory activity against murine mixed lymphocyte reaction 15369399
T-cell IC50 = 0.29 nM 9.54 In vitro evaluation for immunosuppressive activity against proliferation of anti... -
Homo sapiens IC50 = 0.37 nM 9.43 Compound was tested in vitro for inhibition of human mixed lymphocyte proliferat... 9871515
Unchecked IC50 = 0.39 nM 9.41 Relative binding affinity of compound for FK506 binding protein (FKBP) 10425089

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 351
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
10450987 10.1016/s0960-894x(99)00336-4 Rattus norvegicus 12
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
21487055 10.1124/dmd.111.039040 ADMET 10
19015336 10.1128/aac.01154-08 Aspergillus fumigatus 9
21051535 10.1124/dmd.110.034629 ADMET 9
22205779 10.1124/dmd.111.043018 Cytochrome P450 3A4 8
9857082 10.1021/jm980307x Rattus norvegicus 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
22205779 10.1124/dmd.111.043018 Cytochrome P450 3A5 8
20070106 10.1021/jm901371v Homo sapiens 8
21487055 10.1124/dmd.111.039040 UDP-glucuronosyltransferase 1A4 7
17502415 10.1128/aac.01394-06 Aspergillus fumigatus 6
15369399 10.1021/jm031101l Rattus norvegicus 6
7537331 10.1021/jm00008a001 Rattus norvegicus 6
20966043 10.1124/dmd.110.035105 Nuclear receptor subfamily 1 group I member 2 5
17664323 10.1128/aac.00492-07 Trichophyton mentagrophytes 5
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 5
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 5

Data from ChEMBL 36 via Core Engine