CP-96345

CP-96345 : Antagonist of TACR1

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

TACR1

Antagonist

100 nM

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: P25103

Target Class: GPCR

Target SubClass: NK-1 Receptor

Potency: IC50

Potency Value: 0.2 nM

Potency Assay: displacement of 125I-labelled substance P from cloned receptor expressed in CHO cells

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

Target aliases:

Substance-P receptor, TAC1R, NK1R, TACR1, NK1R_HUM ...

DOI Reference: 10.1021/jm00066a015

Uniprot ID: P25103

Target Class: GPCR

Target SubClass: NK-1 Receptor

Potency: Ki

Potency Value: 0.4 nM

Potency Assay: Radioligand Binding Affinity of NK Antagonists in Membrane Preparations from HEK293 Cells Transiently Expressing hNK1-WT

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

Target aliases:

Substance-P receptor, TAC1R, NK1R, TACR1, NK1R_HUM ...

DOI Reference: 10.1021/jm2017072

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): 1- Inhibition of substance P-induced contraction of rabbit vena cava (RVC) tissue - NK-1 (RVC) pA 9.0 2- Inhibition of neurokinin A-induced contraction of rabbit pulmonary artery (RPA) tissue - NK-2 (RPA) pA 4.3 3- Inhibition of neurokinin B induced contraction of rat portal vein (RPV) tissue - NK-3 (RPV) pA 5.6 DOI: 10.1021/jm950616c

Potency assay (off target): Ki > 10,000 nM

Probe Selectivity in Vitro:

Radioligand Binding Affinity of NK Antagonists in Membrane Preparations from HEK293 Cells Transiently Expressing hNK3-WT

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Very little selectivity assessment of this probe, other than voltage-gated L-type Ca channel activity (IC50 240 nM) which corresponds to its cardiovascular toxicity (Williams et al BMCL 1994). The probe has high lipophilicity and basicity likely translating to high potential for off-target effects, which has not been explored.

(last updated: 13 May 2023 )

SERP Ratings

In Cell Rating

(last updated: 18 May 2023 )

SERP Ratings

In Cell Rating

SERP Comments:

The literature around this compound is somewhat conflicting. The compound has undesirable Ca channel activity (but it is the earliest clinical molecule in this space). I would recommend later NK1 antagonists such as L754030 / MK869 / aprepitant as a better chemical probe.

(last updated: 2 Jun 2023 )