BI-9627

Protein target name:

SLC9A1

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 5 µM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

Solute Carrier Proteins

Subclass:

SLC Family

HUGO ID:

HGNC:11071

Entrez gene ID:

6548

UNIPROT ID:

P19634

Target alias:

APNH; NHE1; LIKNS; NHE-1; PPP1R143

Probe Details

Chemical Probes Portal ID:

CPP2327

Probe alias:

cpd 60

PubChem CID:

51031001

ChEMBL ID:

CHEMBL2170610

SMILES string:

CC(N1CCC(CC1)c1ccc(cc1C(F)(F)F)C(NC(N)=N)=O)=O

InChi Key:

QMHRLXNEGYTSRV-UHFFFAOYSA-N

Control compound:

BI-0054

Physico-chemical properties

Solubility - concentration:

90.5 µg/ml

NMR:

1H-NMR (500 MHz, DMSO-d6, 300K) δ = 8.35 (d, 4J = 1.7 Hz, 1H), 8.24 (dd, J = 8.2, 1.7 Hz, 1H), 8.03 (s, 2H), 7.65 (d, 3J = 8.2 Hz, 1H), 7.05 – 6.52 (m, 2H), 4.56 (dt, J = 13.0, 2.2 Hz, 1H), 3.94 (dt, J = 13.7, 2.2 Hz, 1H), 3.19 – 3.04 (m, 2H), 2.61 – 2.53 (m, 1H), 2.04 (s, 3H), 1.83 – 1.66 (m, 3H), 1.62 – 1.51 (m, 1H) ppm

13C-NMR (126 MHz, DMSO-d6, 300K) δ = 173.9, 168.0, 146.5, 137.5, 132.4, 128.4, 126.0 (q, J = 28.8 Hz), 125.5 (q, J = 5.9 Hz), 124.7 (q, J = 273.9 Hz), 46.3, 41.3, 38.2, 33.2, 32.7, 21.3 ppm

Validation in Cells and Model Organisms

In vitro validation

On target activity

Structure-activity relationship:

yes

In cell validation

On target activity in cells

Potency in cells:

IC50

6 nM pHi, 31 nM hPSA

Potency assay (cells):

intracellular pH recovery (pHi) and human platelet swelling (hPSA) assays

Off target activity in cells

Probe Selectivity in Cell:

Solute carrier family 9 isoform selectivity: > 30-fold selective versus SLC9A2 (IC50 = 231 nM) and > 1000-fold versus SLC9A3 (IC50 > 16 µM)

Outside target family: Eurofins-Panlabs screen on 68 targets @ 10 µM did not give strong hits. Clean GPCR scan with the closest hit on SLC6A3 (pKi = 5.8)

In vivo validation

Organism:

Rat, Dog

Dose:

1 mg/Kg IV, 1-5 mg/Kg PO

Route of delivery:

OralIntravenous

Plasma half life:

3.2 (R), 6.2 (D) h

Systemic clearance:

5.7 (R), 13 (D) %QH

Vss:

0.76 (R), 1.4 (D) L/Kg

Bioavailability:

73 (R), 33 (D) %

Primary Reference

Reference (doi):

10.1021/jm300601d

Reference (PMID):

22803959

External Resources

Available data:

SGC Chemical Probes

BI-9627

Probe Availability

Probe Information

Target Details

APNH; NHE1; LIKNS; NHE-1; PPP1R143

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?

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BI-9627

Probe Availability

Probe Information

Target Details

APNH; NHE1; LIKNS; NHE-1; PPP1R143

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?