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In this work, the capability of new materials PILC’s synthesized from montmorillonite as support for catalysts based on Rh or Sn promoted Rh has been studied. Rh based catalysts were synthesized by hydrogen reduction at atmospheric pressure for a cationic organo-metallic rhodium complex. The influence of the supports in the incorporation of the active phase has been studied. The catalysts have been tested in the hydrogenation of crotonaldehyde in the vapor phase at atmospheric pressure, analyzing the effect of some working parameters in the formation of the reaction products, namely the temperature of metal reduction, the reaction temperature, and the addition of Sn as a promoter. For comparative purposes, natural clay and commercial silica have also been used as supports. Both the natural clays and the PILC’s materials have resulted adequate supports for the Rh catalysts. The addition of Sn as a promoter modifies the selectivity leading to higher conversion towards crotyl alcohol.

Goals of investigation : The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) has remained at <5% for decades because no effective therapies have been identified. Integrin αvβ6 is overexpressed in most PDAC and represents a promising therapeutic target. Thus, we attempted to develop an αvβ6-specific peptide-drug conjugate (PDC) for therapy of PDAC. Methodology : We conjugated the DNA-binding pyrrolobenzodiazepine (PBD)-based payload SG3249 (tesirine) to an αvβ6-specific 20mer peptide from the VP1 coat protein of foot-and-mouth-disease virus (FMDV) (forming conjugate SG3299) or to a non-targeting peptide (forming conjugate SG3511). PDCs were tested for specificity and toxicity on αvβ6-negative versus-positive PDAC cells, patient-derived cell lines from tumor xenografts, and on two different in vivo models of PDAC. Immunohistochemical analyses were performed to establish therapeutic mechanism. Results : The αvβ6-targeted PDC SG3299 was significantly more toxic (up to 78-fold) for αvβ6-expressing versus αvβ6-negative PDAC cell lines in vitro , and achieved significantly higher toxicity at equal dose than the non-targeted PDC SG3511 (up to 15-fold better). Moreover, SG3299 eliminated established (100mm 3 ) Capan-1 PDAC human xenografts, extending the lifespan of mice significantly (P=0.005). Immunohistochemistry revealed SG3299 induced DNA damage and apoptosis (increased γH2AX and cleaved caspase 3, respectively) associated with significant reductions in proliferation (Ki67), β6 expression and PDAC tumour growth. Conclusions : The FMDV-peptide drug conjugate SG3299 showed αvβ6-selectivity in vitro and in vivo and can specifically eliminate αvβ6-positive cancers, providing a promising new molecular- specific therapy for pancreatic cancer., Competing Interests: Competing Interests: Philip Howard, Francesca Zammarchi, Patrick H. van Berkel and John A. Hartley are employees and/or shareholders of ADC Therapeutics. All other authors declare no conflicts of interest., (© The author(s).)