Berzosertib

Berzosertib (VE-822, VX-970, M6620) is a drug originally invented by Vertex Pharmaceuticals and licensed to Merck KGaA, Darmstadt, Germany, for development. It acts as a potent inhibitor of the enzyme ataxia telangiectasia and Rad3 related (ATR) and with lower potency as an inhibitor of ATM serine/threonine kinase (ATM). These enzymes are both involved in detecting DNA damage as part of cell cycle checkpoints during cell division. By inhibiting their activity, berzosertib interferes with the ability of rapidly dividing cells to detect damage to DNA, and this makes it useful as a potential treatment for some forms of cancer by causing accumulation of DNA damage in the cancer cells and thus reducing their viability. It has progressed furthest in trials for the treatment of ovarian cancer, though also shows activity against numerous other cancer types.^[1][2][3]

Berzosertib

Clinical data
ATC code	None
Identifiers
IUPAC name 3-[3-[4-(methylaminomethyl)phenyl]-5-isoxazolyl]-5-(4-propan-2-ylsulfonylphenyl)-2-pyrazinamine
CAS Number	1232416-25-9
PubChem CID	59472121
DrugBank	DB11794
ChemSpider	30773968
UNII	L423PRV3V3
KEGG	D11148
ChEBI	CHEBI:131166
CompTox Dashboard (EPA)	DTXSID601025940
Chemical and physical data
Formula	C24H25N5O3S
Molar mass	463.56 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)S(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C3=CC(=NO3)C4=CC=C(C=C4)CNC)N
InChI InChI=1S/C24H25N5O3S/c1-15(2)33(30,31)19-10-8-18(9-11-19)21-14-27-24(25)23(28-21)22-12-20(29-32-22)17-6-4-16(5-7-17)13-26-3/h4-12,14-15,26H,13H2,1-3H3,(H2,25,27) Key:JZCWLJDSIRUGIN-UHFFFAOYSA-N

Phase 1 trial results show promising results in the first clinical trial of the drug class. The new study, designed to test the drug's safety, found that half of patients given the new drug either alone or with platinum chemotherapy saw their cancer stop growing, and two patients saw their tumors shrink or disappear completely.^[4][5]

In a UCLA-led study, berzosertib showed promise in treating COVID-19.^[6]