Abstract: The present disclosure provides novel pladienolide compounds, pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancers, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are methods of treating cancers by administering at least one compound disclosed herein and at least one additional therapy.

Abstract: In a wire harness, a frame includes a partition wall. The partition wall includes a locking part that locks a joint connector housed in a sectioned space part from an opening part on the lower side. When an electronic component block is being fixed to a frame by a fixing part, the locking part is positioned on the lower side than the electronic component block is and isolated from the electronic component block in the orthogonal direction that is orthogonal to the insertion direction (first height direction) of the electronic component block when the frame is viewed from the opening part on the lower side.

Abstract: The present disclosure provides novel pladienolide compounds, pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancers, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are methods of treating cancers by administering at least one compound disclosed herein and at least one additional therapy.

Abstract: Linker-drug compounds and antibody-drug conjugates that bind to human oncology targets are disclosed. The linker-drug compounds and antibody-drug conjugates comprise a herboxidiene splicing modulator drug moiety. The disclosure further relates to methods and compositions for use in the treatment of neoplastic disorders by administering the antibody-drug conjugates provided herein. The herboxidiene itself is also claimed. Further claims are directed to its use, and to the use of a neoantigen, generated by the herboxidiene or its ADC, or a vaccine against this neoantigen.

Abstract: The present disclosure provides novel pladienolide compounds, pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancers, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are methods of treating cancers by administering at least one compound disclosed herein and at least one additional therapy.

Abstract: The present disclosure provides a novel solid state form of pladienolide pyridine compounds, compositions comprising at least one such solid state form, and methods of preparation and use and the same. The novel solid state form of pladienolide pyridine compounds may be useful in the treatment of cancer, such as, for example, cancers in which agents that target the spliceosome and mutations therein are known to be useful.

Abstract: The present disclosure provides a novel solid state form of pladienolide pyridine compounds having Formula I, compositions comprising at least one such solid state form, and methods of preparation and use and the same. The novel solid state form of pladienolide pyridine compounds may be useful in the treatment of cancer, such as, for example, cancers in which agents that target the spliceosome and mutations therein are known to be useful.

Abstract: The present disclosure provides a novel solid state form of pladienolide pyridine compounds, compositions comprising at least one such solid state form, and methods of preparation and use and the same. The novel solid state form of pladienolide pyridine compounds may be useful in the treatment of cancer, such as, for example, cancers in which agents that target the spliceosome and mutations therein are known to be useful.

Abstract: The present invention provides novel pladienolide pyridine compounds, pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful.

Abstract: The present invention provides novel pladienolide pyridine compounds, pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful.

Abstract: The present invention provides quaternary salts, such as those of Formula I: as well as the use thereof in methods of treatment for cancer.

Abstract: In a caliper type brake for bicycles, a coil spring is inserted between the connecting portions of a Bowden cable at ends of opposite brake blocks formed in horseshoe-shape so as to drive both blocks in stretched state. A limiting tool is fitted to a through bolt for pivoting both blocks so as to define the turned position of both blocks, and a spanner-attaching tool is also fitted to the through bolt so as to adjust the turned position of the bolt.

Abstract: In a caliper type brake for bicycles, spring adjusting devices provided with grooves stepwise on the surface are inserted to both supporting portions of a return spring which drives right and left brake blocks to be stretched outwards, that is, to the engaging portions of the return spring with the spring supports. The clearance from right and left brake rubbers to the rim may be equalized by changing the engaging portions of the spring supports with a plurality of grooves of different heights constituted on the spring adjusting devices.