ART812

• CAT Number: I044429
• CAS Number: 2607138-82-7
• Molecular Formula: C19H16ClF4N3O4
• Molecular Weight: 461.79
• Purity: ≥95%
• Synonyms: (2S,3S,4S)-N-(3-chloro-4-fluorophenyl)-3,4-dihydroxy-N-methyl-1-[6-methyl-4-(trifluoromethyl)pyridin-2-yl]-5-oxopyrrolidine-2-carboxamide
• InChI: InChI=1S/C19H16ClF4N3O4/c1-8-5-9(19(22,23)24)6-13(25-8)27-14(15(28)16(29)18(27)31)17(30)26(2)10-3-4-12(21)11(20)7-10/h3-7,14-16,28-29H,1-2H3/t14-,15-,16-/m0/s1
• InChIKey: YJJOABOMFPGRED-JYJNAYRXSA-N
• SMILES: CC1=CC(=CC(=N1)N2C(C(C(C2=O)O)O)C(=O)N(C)C3=CC(=C(C=C3)F)Cl)C(F)(F)F

ART812 is an orally active DNA polymerase Polθ inhibitor with an IC50 value of 7.6 nM. ART812 has an IC50 value of 240 nM for cell based microhomology-mediated end joining (MMEJ)[1][2].
ART812 (0-40 μM) elicits Polθ inhibitor sensitivity in MDA-MB-436 SHLD2 knockout cells[1].
ART812 (100 mg/kg; p.o. daily for 76 days) shows significant tumour inhibition in rats bearing established MDA-MB-436 BRCA1/SHLD2 defective tumours (volume 250-350 mm3)[1].

Reference

[1]. Zatreanu D, et al. Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance. Nat Commun. 2021 Jun 17;12(1):3636.
 [Content Brief]

[2]. Peter BLENCOWE, et al. Preparation of heterocyclic compounds for use in the treatment of cancer. WO2021028643 A1.