BAY-9835

BAY-9835 : Inhibitor of ADAMTS7, ADAMTS12

Structure

SERP Rating

In Cells

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In Model Organisms

(1 ratings)

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Probe BAY-9835 is in the process of SERP review.

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Information

ADAMTS7
ADAMTS12

Inhibitor

100 nM

Additional Data

SGC image SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: Q9UKP4

Target Class: Enzyme

Target SubClass: Disintegrin

Potency: IC50

Potency Value: 6 nM

Potency Assay: Biochemical enzymatic assay

PDB ID for probe-target interaction (3D structure): 8RIJ

Target aliases:

A disintegrin and metalloproteinase with thrombosp ...

DOI Reference: 10.1021/acs.jmedchem.3c02036

In Cell Validations

No in Cell Validations available

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Within target family: Protease panel IC50 [µM]: hADAMTS4 (6.726), hADAMTS5 (9.924), hADAM8 (2.25), hADAM10 (32.802), hADAM17 (5.772), hMMP12 (5.376), hMMP15 (78.474), hMMP2, hMMP14, CAPN1 (Calpain 1), CASP3 (Caspase3), CTSB (Cathepsin B), CTSS (Cathepsin S), MALT1 all > 10 µM. Outside target family: Eurofins Panlabs panel (77 targets) at 10 µM: clean. In-house kinase panel (12): all IC50 > 20 µM

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SERP ratings and comments

SERP Ratings

In Model Organisms

SERP Comments:

This probe targets an extracellular protein and therefore does not require an intracellular evaluation. Good biochemical activity on ADAMTS7 and ADAMTS12 with high selectivity over related proteins. Biochemical activity and PK data for BAY-9835 indicate sufficient exposure for model organism probe use. Higher exposures were obtained using aqueous vehicle Solutol HS 15/ethanol/water 40/10/50 (solubility 30 g/L). Worth noting that Bayer suggest an "an oral dose of 30 mg/kg BAY-9835 once daily to mice or rats might cover respective IC50’s for 24 h" but oral data is only provided for 1 mg/kg. In addition, on-cell potency was reported for close analogue (compound 29 from J. Med. Chem. 2024, 2907) but not for BAY-9835 itself. Data for compound 29 and negative control compound BAY-1880 is provided in Bayer presentation (https://www.sgc-ffm.uni-frankfurt.de/APP/connector/1/352/url/BAY-9835+Inhibitor+for+ADAMTS7+and+ADAMTS12.pdf).

(last updated: 21 Nov 2024 )