Tacrolimus

Protein target name:

FKBP1A

Mechanism of action:

FKBP-Tacrolimus inhibitor complexMolecular Glue

Recommended Concentration for use in cells:

up to 1 uM

Probe Availability

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

Isomerase

Subclass:

Immunophilin Protein Family

HUGO ID:

HGNC:3711

Entrez gene ID:

2280

UNIPROT ID:

P62942

Target alias:

FKBP1; PKC12; PKCI2; FKBP12; PPIASE; FKBP-12; FKBP-1A

Probe Details

Chemical Probes Portal ID:

CPP783

Probe alias:

Prograf, Protopic, Tsukubaenolide, Advagraf, FK-506, FK506, FK 506, FR900506, Fujimycin, FK5, Molecular-Glue

PubChem CID:

445643

ChEMBL ID:

CHEMBL269732

SMILES string:

O=C([C@@](CCCC1)([H])N1C(C([C@@]2(O)[C@H](C)C[C@H](OC)[C@@](O2)([H])[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H]3CC=C)=O)=O)O[C@H](/C(C)=C/[C@H]4C[C@@H](OC)[C@H](O)CC4)[C@H](C)[C@@H](O)CC3=O

InChi Key:

QJJXYPPXXYFBGM-LFZNUXCKSA-N

Physico-chemical properties

Potential reactivities:

Tacrolimus contains two reactive hydroxyl groups, namely, at the O−C(24) and the O−C(32) positions.

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.4 nM

Potency assay:

Spectrophotometric Assay (Fisher Assay)

PDB ID for probe-target interaction (3D structure):

1FKF

Structure-activity relationship:

Off target activity

Potency (off target):

Off target protein and potency:

FKBP12.6 0.55 nM, FKBP37 4 nM, FKBP52 10 nM, CyP-A 2 nM, CyP-C 4 nM, CyP-D 3.6 nM

Probe Selectivity in Vitro:

Activity (Ki) against FKBP human immunophilins: FKBP12.6 0.55 nM, FKBP13 38 nM, FKBP25 160 nM, FKBP37 4 nM and FKBP52 10 nM. Activity (Ki) against human Cyclophilins CyP-A 2 nM, CyP-B 84 nM, CyP-C 4 nM, CyP-D 3.6 nM, CyP-40 300 nM, and CyP-NK N/A.

In cell validation

On target activity in cells

Potency in cells:

IC50

0.19 nM IL-2 RGA, 0.29 nM MLR, 0.18 nM T-cell, 0.06 nM IL-5, 0.06 nM IFN-γ, 0.95 nM MBA-12

Potency assay (cells):

IL-2 reporter gene assay, Murine MLR assay, PPD-induced proliferation of HPBMNC isolated from blood, IL-5 production assay (WB), IFN-γ production assay (WB), Macrophilin-12 (FKBP-12) binding assay

In vivo validation

Organism:

Rat

Dose:

1, 2, 5, 10 mg/Kg

Route of delivery:

OralIntravenousSubcutaneous

Plasma half life:

6.4 h

Systemic clearance:

1.59 L/h/Kg

Cmax:

41 ng/mL

Tmax:

0.25 h

Organ of Interest

Target engagement assay:

Allergen OA-induced eosinophil influx inhibition (ED50 0.3 mg/Kg)

Primary Reference

Reference (doi):

10.1021/jm980307x 10.1073/pnas.89.9.3686 10.2133/dmpk.22.328 10.1021/jm031101l

Reference (PMID):

7530743 9857082 1373887 17965516 15369399

Tacrolimus

Probe Availability

Probe Information

Target Details

FKBP1; PKC12; PKCI2; FKBP12; PPIASE; FKBP-12; FKBP-1A

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Tacrolimus

Probe Availability

Probe Information

Target Details

FKBP1; PKC12; PKCI2; FKBP12; PPIASE; FKBP-12; FKBP-1A

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?