A DNA polymerase θ inhibitor
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ART558

Item No. 42324

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
(2S,3R)-1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-3-hydroxy-N-methyl-N-(3-methylphenyl)-2-pyrrolidinecarboxamide
CAS Number
2603528-97-6
Molecular Formula
C21H21F3N4O2
Formula Weight
418.4
Purity
≥98%
Formulation
A solid
Solubility(Learn about Variance in Solubility)
DMSO: Soluble: ≥10 mg/mlEthanol: Sparingly Soluble: 1-10 mg/ml
SMILES
O[C@@H]1CCN(C2=NC(C)=CC(C(F)(F)F)=C2C#N)[C@@H]1C(N(C3=CC(C)=CC=C3)C)=O
InChi Code
InChI=1S/C21H21F3N4O2/c1-12-5-4-6-14(9-12)27(3)20(30)18-17(29)7-8-28(18)19-15(11-25)16(21(22,23)24)10-13(2)26-19/h4-6,9-10,17-18,29H,7-8H2,1-3H3/t17-,18+/m1/s1
InChi Key
YHMDHAMZFMNMTF-MSOLQXFVSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    5 mg

    $219

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    10 mg

    $350

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    25 mg

    $657

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    50 mg

    $1,095

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    Cayman Chemical
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    Product Description

    ART558 is an inhibitor of DNA polymerase θ (Polθ; IC50 = 7.9 nM for Polθ polymerase activity).1,2 It is selective for the polymerase activity of Polθ over its ATPase activity (IC50 = >12 µM).2 ART558 (0.1, 0.3, and 1 µM) inhibits the repair of DNA double-strand breaks via theta-mediated end joining (TMEJ), but not non-homologous end joining (NHEJ), in a reporter assay using an extrachromosomal DNA substrate.1 It induces synthetic lethality in RPE1 cells lacking BRCA1 and DLD-1 cells lacking BRCA2. ART558 also reduces tumor growth in a 3D organoid culture model using cells derived from patients with BRCA1-low, 53BP1-low prostate cancer.

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Zatreanu, D., Robinson, H.M.R., Alkhatib, O., et al. Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance. Nat. Commun. 12(1), 3636 (2021).

    2. Stockley, M.L., Benedetti, G., Blencowe, P., et al. Discovery, characterization, and structure-based optimization of small-molecule in vitro and in vivo probes for human DNA polymerase theta. J. Med. Chem. 65(20), 13879-13891 (2022).