Tuesday, June 2, 2015

Drugs in Clinical Pipeline: SAR103168

SAR103168 is a novel multi-targeted kinase inhibitor of the Src kinase family (SKF), the Bcr-Abl kinase and several angiogenic receptor kinases such as vascular endothelial growth factor receptor type 1 and type 2 (VEGFR1 and VEGFR2), Tie2, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and epidermal growth factor receptor (EGFR).

SAR103168 is supplied for i.v. administration. SAR103168 is active in various Acute Myeloid Leukemia (AML) models including immature CD34+ AML cells expressing functional P-glycoprotein (P-gp). SAR103168 was developed to target immature AML cells that are generally believed to be a reservoir of chemo-resistant AML progenitor malignant cells. It is thought that this reservoir of malignant cells refuels the AML cell clones and triggers the relapse after front-line therapy. The effect of SAR103168 on both tumor cells and bone marrow angiogenesis in preclinical studies warrants clinical investigation of the anti-leukemia efficacy of the drug in this difficult-to-treat patient population.

Common Name: SAR103168
Synonyms: SAR103168; SAR 103168; SAR-103168
IUPAC Name: -
CAS Number: -
Mechanism of Action: Multi-Kinase Inhibitor
Indication: Various Cancers; Acute Myeloid Leukemia (AML)
Development Stage: Phase I
Company: Sanofi

Eidogen Sertanty Inc Provides Kinase Knowledge Base (KKB): a Collection of nearly 1.6 M Kinase Inhibitors.

In vitro, SAR103168 has nanomolar potency, specifically against the proliferation of immature CD34+ AML leukemia cells expressing functional P-gp. Compared to cytarabine, dasatinib or tipifarnib, SAR103168 has a larger spectrum of activities on immature AML cells. In vivo, SAR103168 demonstrates very potent antitumor efficacy in several AML or CML models when assessed via multiple administration routes. Preclinical efficacy is improved in AML models compared to Tipifamib and Dasatinib previously developed in the same indication.

In a Phase I Dose-escalation, Safety and Pharmacokinetic Study of SAR103168 in Patients Refractory/Relapsed Acute Leukemias or High-risk Myelodysplastic Syndromes; SAR103168 is administrated as a single agent by intravenous infusion, once daily for 5 days. Based on pharmacokinetic considerations, the dose-escalation portion of the study was discontinued prior to reaching MTD and further development of the compound was halted internally.