Relacatib

Protein target name:

CTSK, CTSL, CTSV

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

~~up to 500 nM~~

Reviewer suggested Concentration for use in cells:

up to 1 uM

Probe Availability

MedKoo Biosciences, Inc.

Probe Information

Target and Probe Information

Target Details

Target class:

Protein metabolism

Subclass:

Protease

HUGO ID:

HGNC:2536 HGNC:2537 HGNC:2538

Entrez gene ID:

1513 1514 1515

UNIPROT ID:

P43235 P07711 O60911

Target alias:

CTSO; PKND; PYCD; CTS02; CTSO1; CTSO2; MEP; CATL; CTSL1; CTSU; CATL2; CTSL2

Probe Details

Chemical Probes Portal ID:

CPP2068

Probe alias:

SB-462795, GSK-462795, cpd 10

PubChem CID:

6918602

ChEMBL ID:

CHEMBL203665

SMILES string:

CC(C[C@@H](C(=O)N[C@H]1CC[C@H](N(CC1=O)S(=O)(=O)c1ccccn1)C)NC(=O)c1cc2c(o1)cccc2)C

InChi Key:

BWYBBMQLUKXECQ-GIVPXCGWSA-N

Physico-chemical properties

NMR:

1H NMR (CDCl3) δ 8.72 (d, J = 4.5 Hz, 1H), 8.0 (d, J = 7.8 Hz, 1H), 7.93 (ddd, J = 7.7, 7.7, 1.5 Hz, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.56 (m, 2H), 7.45 (s, 1H), 7.42 (dd, J = 8.1, 7.3 Hz, 1H), 7.28 (dd, J = 7.6, 7.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.85 (d, J = 6.4 Hz, 1H), 5.15 (m, 1H), 4.77 (d, J = 19.5 Hz, 1H), 4.68 (m, 1H), 4.40 (m, 1H), 3.86 (d, J = 19.5 Hz, 1H), 2.20−2.08 (m, 2H), 1.78−1.40 (m, 5H), 0.98 (m, 9H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.041 nM

Potency assay:

Cathepsin K Proteolytic Catalytic Activity assay

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

2FTD

Structure-activity relationship:

yes

Off target activity

Potency (off target):

Off target protein and potency:

CTSS 1.6 nMCTSB 13 nM

Probe Selectivity in Vitro:

Exhibits 39–300-fold selectivity over other cathepsins.

In cell validation

On target activity in cells

Potency in cells:

IC50

22 nM, 45 nM, ~70 nM

Potency assay (cells):

in vitro osteoclast resorption assay, osteoclast cathepsin activity inhibition, bone resorption inhibition

In vivo validation

Organism:

male Sprague−Dawley ratMale cynomolgus monkey

Dose:

1-2 (IV), 2-4 (PO) mg/KgReviewer Suggest 3-30 mg/Kg

Route of delivery:

OralIntravenous

Plasma half life:

109 (R), 168 (M) min

Systemic clearance:

19.5 (R), 11.7 (M) mL/min/kg

Fraction of probe bound to plasma protein:

96.8 %

Primary Reference

Reference (doi):

10.1021/jm050915u 10.1016/j.bone.2006.07.015

Reference (PMID):

16509577 16962401

Relacatib

Probe Availability

Probe Information

Target Details

CTSO; PKND; PYCD; CTS02; CTSO1; CTSO2; MEP; CATL; CTSL1; CTSU; CATL2; CTSL2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Relacatib

Probe Availability

Probe Information

Target Details

CTSO; PKND; PYCD; CTS02; CTSO1; CTSO2; MEP; CATL; CTSL1; CTSU; CATL2; CTSL2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?