Saridegib, also known as IPI-926, is an experimental drug candidate undergoing clinical trials for the treatment of various types of cancer, including hard-to-treat hematologic malignancies such as

myelofibrosis Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in ...

and ligand-dependent tumors such as

chondrosarcoma Chondrosarcoma is a bone sarcoma, a primary cancer composed of cells derived from transformed cells that produce cartilage. A chondrosarcoma is a member of a category of tumors of bone and soft tissue known as sarcomas. About 30% of bone sarco ...

. IPI-926 exhibits its pharmacological effect by inhibition of the

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

smoothened Smoothened is a protein that in humans is encoded by the ''SMO'' gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the mole ...

, a component of the

hedgehog signaling pathway The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathwa ...

. Chemically, it is a semi-synthetic

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

of the

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

cyclopamine Cyclopamine (11-deoxojervine) is a naturally occurring steroidal alkaloid. It is a teratogenic component of corn lily ('' Veratrum californicum''), which when consumed during gestation has been demonstrated to induce birth defects, including the ...

. The process begins with

extracted from harvested

Veratrum californicum ''Veratrum californicum'' (California corn lily, white or California false hellebore) is an extremely poisonous plant native to western North America, including the Sierra Nevada and Rocky Mountains, as far north as Washington and as far south ...

which is taken through a series of alterations resulting in an analogue of the natural product cyclopamine, making IPI-926 the only compound in development/testing that is not fully synthetic. Saridegib is a member of a class of anti-cancer compounds known as

hedgehog pathway inhibitors Hedgehog pathway inhibitors, also sometimes called hedgehog inhibitors, are small molecules that inhibit the activity of a component of the Hedgehog signaling pathway. Due to the role of aberrant Hedgehog signaling in tumor progression and cancer s ...

References

{{reflist Jervines teratogens Spiro compounds Sulfonamides Experimental cancer drugs