AZD0095 / AstraZeneca - LARVOL DELTA

Discovery of Clinical Candidate AZD0095, a Selective Inhibitor of Monocarboxylate Transporter 4 (MCT4) for Oncology. (PubMed, J Med Chem) - "Minor modifications to the triazolopyrimidine were made, alongside design of a constrained linker and broad SAR exploration of the biaryl tail to improve potency, physical properties, PK, and hERG. The resulting clinical candidate 15 (AZD0095) has excellent potency (1.3 nM), MCT1 selectivity (>1000×), secondary pharmacology, clean mechanism of action, suitable properties for oral administration in the clinic, and good preclinical efficacy in combination with cediranib."

Journal • Oncology

INHIBITION OF LACTATE EXPORTERS INDUCES DIRECT ANTI-TUMOR EFFECTS AND COUNTERS IMMUNE SUPPRESSION IN MULTIPLE MYELOMA (EHA 2022) - "Syrosingopine was used as dual inhibitor of MCT1 and MCT4, AZD0095 as MCT4 inhibitor and AZD3965 as MCT1 inhibitor...AZD0095 and AZD3965 were less potent to induce cell death in combination with metformin, compared to dual MCT inhibition...Targeting lactate metabolism could be a new approach to hamper MM survival and create a less suppressive immune environment. Arne Van der Vreken and Inge Oudaert contributed equally to this work."

Hematological Malignancies • Multiple Myeloma • Oncology • ANXA5 • ITGAM • MCT1 • STAT3

Reversing lactate-driven immunosuppression using the novel, potent and selective MCT4 inhibitor AZD0095 (AACR 2019) - "Consistent with the observed changes in immune cell infiltration, the combination of AZD0095 with checkpoint inhibitors α-PD1 or α-CTLA4 (10 mg/kg 3x week) enhances the anti-tumor activity of checkpoint inhibitor monotherapy in MC-38 and EMT6 (MCT1 knock-out) mouse syngeneic models. These data demonstrate that AZD0095 can reverse lactate-driven immunosuppression and enhance response to checkpoint inhibition in pre-clinical models."

Newly added product (AACR 2019) - Preclinical, Oncology

Pipeline update