LNP-023

Inhibitor of CFB

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe LNP-023 is in the process of SERP review.

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Information

Inhibitor

up to 1 uM

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Probe Availability:

In Vitro Validations

Uniprot ID: P00751

Target Class: Other

Target SubClass: Serine Protease

Potency: Kd

Potency Value: 7.9 nM

Potency Assay: SPR

PDB ID for probe-target interaction (3D structure): 6RAV

Structure-activity relationship: yes, check DOI: 10.1021/acs.jmedchem.9b01870

Target aliases:

Complement factor B, BFD, BF, CFB, CFAB_HUMAN, GBG ...

DOI Reference: 10.1073/pnas.1820892116

Uniprot ID: P00751

Target Class: Other

Target SubClass: Serine Protease

Potency: IC50

Potency Value: 12 nM

Potency Assay: Half-maximal inhibition of human FB in TR-FRET based competition binding assay (FB-comp)

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

Target aliases:

Complement factor B, BFD, BF, CFB, CFAB_HUMAN, GBG ...

DOI Reference: 10.1073/pnas.1820892116

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

IC50 values of >30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM)

Probe Selectivity in Cell:

LNP023 provided IC50 values of >30 μM across an internal panel of ∼110 enzymes, receptors, and ion channels, including hERG and adrenergic receptors α1a and α2c

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

LNP023 is a first in class, potent reversible inhibitor of the serine protease factor B (FB). This protease is a key component of the alternative complement pathway. This pathway is dysregulated in a number of diseases, and a number of targets in the pathway are active subjects of drug discovery programs. The compound was optimized using structure-based drug design and a number of useful crystal structures have been deposited. LPN023 has IC50 values >30 micromolar for 41 other proteases tested. The selectivity is likely due to unique features of the FB active site. It also is inactive (IC50>30 micromolar) across a panel of 110 enzymes, receptors, and ion channels. It exhibits the expected on-target pharmacology and in vivo activity. Phase 1 trials have been completed and it is in phase 2 trials for several diseases.

(last updated: 12 Mar 2021 )