AB680

Protein target name:

CD73

Mechanism of action:

Reversible Competitive Inhibitor

Recommended Concentration for use in cells:

~~200 nM~~

Reviewer suggested Concentration for use in cells:

0.4–4 nM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

Ecto-Nucleotidase

Subclass:

Membrane Protein

HUGO ID:

HGNC:8021

Entrez gene ID:

4907

UNIPROT ID:

P21589

Target alias:

NT; eN; NT5; NTE; eNT; CD73; E5NT; CALJA

Probe Details

Chemical Probes Portal ID:

CPP1877

Probe alias:

AB-680, Compound 55

PubChem CID:

130205852

SMILES string:

O=P(CP(O)(O)=O)(O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(N=C(Cl)C=C3N[C@H](C4=CC=CC=C4F)C)=C3C=N2)O1

InChi Key:

MFYLCAMJNGIULC-KCVUFLITSA-N

Physico-chemical properties

NMR:

1H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 8.23 (d, J = 6.9 Hz, 1H), 7.42 – 7.34 (m, 1H), 7.33 – 7.09 (m, 3H), 6.06 (d, J = 4.3 Hz, 1H), 5.97 (s, 1H), 5.04 (s, 1H), 4.53 – 4.47 (m, 1H), 4.25 (t, J = 4.7 Hz, 1H), 4.13 – 3.97 (m, 2H), 3.92 – 3.82 (m, 1H), 2.16 (d, J = 20.5 Hz, 2H), 1.56 (d, J = 6.4 Hz, 3H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

Ki, IC50

5 pM, 43 pM

Potency assay:

AMP-Glo assay, Enzymatic reaction

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

6Z9D

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

No off-target activity against the ecto-nucleotidases NTPDase-1 (CD39), -2, -3, and -8 up to 10 µM

In cell validation

On target activity in cells

Potency in cells:

IC50

8 pM hCD8+ T11 pM hPBMC

Potency assay (cells):

Enzymatic Assay

Off target activity in cells

Potency assay, off target (cells):

CEREP

Probe Selectivity in Cell:

Screened against 60 targets in a wide ligand profile screen (CEREP) with no off-target activity observed up to 10 µM

In vivo validation

Organism:

MouseRatDogDonkeyHuman (projected)

Dose:

0.5 mg/Kg16 mg/Kg25 mg/Kg

Route of delivery:

Intravenous

Plasma half life:

3.5(m), 5.3(R), 22(D), 27(M), 98(H) h

Systemic clearance:

25(m), 20(R), 50(D), 0.25(M), 0.12(H) mL/h/Kg

Fraction of probe bound to plasma protein:

fu 0.89%(m), 0.17(R), 8.3(D), 0.59(M), 0.42 %(H) h

Cmax:

3,910 ng/mL @ 16 mg/Kg5,170 ng/mL @ 25 mg/Kg

Primary Reference

Reference (doi):

10.1021/acs.jmedchem.0c00525 10.1021/acs.biochem.9b00448

Reference (PMID):

32614585 31334635

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells and in model organisms.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

High levels of adenosine with the tumor microenvironment inhibit the activation of T cells and NK cells thereby suppressing the immune function. CD73 is ecto-nucleotidase which catalyses the conversion of adenosine monophosphate (AMP) to adenosine. AB680 is a highly selective inhibitor of the ecto-nucleotidase CD73 however it is a triply charged molecule that requires iv delivery. AB680 demonstrates excellent potency (Ki =5 pM). Furthermore, it shows a desirable slow clearance in several animal models including mouse, rat, dog, and monkey.

Sep 5 2020 - 8:49am

AB680

Probe Availability

Probe Information

Target Details

NT; eN; NT5; NTE; eNT; CD73; E5NT; CALJA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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AB680

Probe Availability

Probe Information

Target Details

NT; eN; NT5; NTE; eNT; CD73; E5NT; CALJA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?