D6-3

D6-3 : Covalent Inhibitor of CTSL

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe D6-3 is in the process of SERP review.

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Information

CTSL

Covalent Inhibitor

up to 10 uM

In Vitro Validations

Uniprot ID: P07711

Target Class: Enzyme

Target SubClass: Cysteine protease

Potency: IC50

Potency Value: 0.27 nM

Potency Assay: FRET protease assay

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

Target aliases:

Procathepsin L, CTSL1, CTSL, CATL1_HUMAN, MEP, Maj ...

DOI Reference: 10.1021/acs.jmedchem.4c00656

Uniprot ID: P07711

Target Class: Enzyme

Target SubClass: Cysteine protease

Potency Value: Kinact/Ki 6.83 ± 0.25 × 10*6 S-1 M-1

Potency Assay: Kinetic binding assay

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

Target aliases:

Procathepsin L, CTSL1, CTSL, CATL1_HUMAN, MEP, Maj ...

DOI Reference: 10.1021/acs.jmedchem.4c00656

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): D6-3 inhibitor activity was measured on seven human proteases @ 10 uM. Among them, TMPRSS2, human trypsin (hTrypsin), and human chymotrypsin (hChymotrypsin) are serine proteases, and cathepsin B (CatB), cathepsin V (CatV), cathepsin S (CatS), and caspase 3 are cysteine proteases. D6–3 showed no activities against the three serine proteases or caspase 3.

Probe Selectivity in Vitro:

D6-3 did show inhibition against CatB, CatV, and CatS. Kinact/Ki values of D6–3 for other cathepsins were generally 1 to 3 orders of magnitude lower than those of CatL, indicating that D6–3 exhibits better selectivity for CatL

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The solubility of D6-3 was described as being poor and the formulation for in vivo studies via the i.p route was not disclosed. It is highly recommended that the formulation (s) used by the authors for the in vivo studies be described in detail to facilitate its use by others in vivo.

(last updated: 22 Aug 2025 )