Cambritaxestat

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Cambritaxestat

CAS 1979939-16-6

MFC25H22ClF3N4O2 MW502.9 g/mol

N-[(1S)-1-(4-chlorophenyl)ethyl]-3-[3-[[4-(trifluoromethoxy)phenyl]methyl]imidazo[4,5-b]pyridin-2-yl]propanamide

N-[(1S)-1-(4-chlorophenyl)ethyl]-3-(3-{[4-(trifluoromethoxy)phenyl]methyl}-3H-imidazo[4,5-b]pyridin-2-yl)propanamide
autotaxin inhibitor, antineoplastic, Orphan Drug, IOA 289, IOA-289, IOA289, LYY3P2KA27, CRT 0273750

OriginatorCancer Research Technology; Merck & Co
DeveloperiOnctura
ClassAntifibrotics; Antineoplastics; Small molecules
Mechanism of ActionAngiogenesis inhibitors; Cell proliferation inhibitors; ENPP2 protein inhibitors
Orphan Drug StatusYes – Pancreatic cancer
Phase I/IIPancreatic cancer
Phase ISolid tumours
PreclinicalNon-alcoholic steatohepatitis
14 Oct 2025Efficacy and adverse event data from a phase I/II trial in Pancreatic cancer released by iOnctura
04 Oct 2024Cambritaxestat is still in phase-I development in Solid-tumours (In volunteers) in Italy (PO, Capsule) (NCT05027568)
31 May 2024Efficacy and adverse event data from a phase I/II trial in Pancreatic cancer presented at the 60th Annual Meeting of the American Society of Clinical Oncology (ASCO-2024)

Cambritaxestat is an autotaxin inhibitor.

Cambritaxestat is an orally bioavailable small molecule inhibitor of autotaxin (ATX; ectonucleotide pyrophosphatase/phosphodiesterase family member 2; ENPP2), with potential antifibrotic and antineoplastic activities. Upon oral administration, cambritaxestat targets and binds to both the substrate pocket and the lysophosphatidic acid (LPA) carrier channel of ATX, thereby inhibiting the activity of ATX. This both directly inhibits the proliferation of tumor cells and reduces fibrosis in the tumor microenvironment (TME), allowing lymphocytes to infiltrate into the tumor and enhancing immune responses against tumor cells. ATX, a secreted glycoprotein with lysophospholipase D activity, hydrolyzes lysophosphatidylcholine (LPC) to LPA. LPA-mediated signaling plays an important role in cellular migration, proliferation and survival in fibrotic response. ATX and LPA are overexpressed in many tumors.

A Study to Assess an ATX Inhibitor (IOA-289) in Healthy VolunteersCTID: NCT05027568Phase: Phase 1Status: CompletedDate: 2025-03-20
A Study to Assess an ATX Inhibitor (IOA-289) in Patients with Metastatic Pancreatic CancerCTID: NCT05586516Phase: Phase 1/Phase 2Status: Active, not recruitingDate: 2025-03-20

SYN

WO2016/124939

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2016124939&_cid=P22-MKBYYZ-98558-1

SYN

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=D2AB83A7D50F3F6B36DBA4001867C8E7.wapp2nC?docId=WO2024246264&_cid=P22-MKBYUT-93851-1

WO2016/124939 describes various ATX inhibitor compounds and their use in the treatment of proliferative disorders in which ATX activity is implicated, including Compound 1.

Compound 1 is example 40 in WO2016/124939, which document is incorporated herein by reference in its entirety. WO2016/124939 describes over 200 examples. Compound 1’s structure is according to Formula I.