|This article needs additional citations for verification. (February 2016) (Learn how and when to remove this template message)|
||This article includes inline citations, but they are not properly formatted. (February 2016) (Learn how and when to remove this template message)|
|Jmol 3D model||Interactive image|
|Molar mass||504.77 g·mol−1|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
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 and ligand-dependent tumors such as chondrosarcoma. IPI-926 exhibits its pharmacological effect by inhibition of the G protein-coupled receptor smoothened, a component of the hedgehog signaling pathway. Chemically, it is a semi-synthetic derivative of the alkaloid cyclopamine. The process begins with cyclopamine extracted from harvested Veratrum californicum 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.
|This section needs additional citations for verification. (February 2016) (Learn how and when to remove this template message)|
||This section possibly contains original research. (February 2014) (Learn how and when to remove this template message)|
||This section may require cleanup to meet Wikipedia's quality standards. The specific problem is: details about general class of compounds needs to be reduced or moved to the hedgehog inhibitor or the related signaling article (not here), and no citations appearing until the end of section violates WP:VERIFY (February 2014) (Learn how and when to remove this template message)|
Saridegib is a member of a class of anti-cancer compounds known as hedgehog inhibitors (Hhi). Most of these compounds affect the hedgehog signaling pathway via inhibition of smoothened (Smo), a key component of the pathway. Depending on when a Hh inhibiting compound is approved by the U.S. Food and Drug Administration (FDA), there may be a perceived need for one to be differentiated over another for marketing purposes, which could lead to different nomenclature (e.g., a Hhi or an agonist of Smo). This marketing technique is more of a differentiation strategy than a scientific property of these compounds, as the mechanism of action (MOA) in the end is inhibition of the Hh pathway, targeting cancer stem cells. However, as these new compounds are further studied, identification of differences in a compound's MOA, could lead to hypotheses regarding the stage at which Smo is inhibited, where along the pathway the compound binds, or specific binding properties of a compound. If these hypotheses are proven, claims could be made regarding a specific compound's MOA and how it affects efficacy, safety, combinability with other cancer treatments, etc. Scientific data in support of such hypotheses have not been published to date.
There are currently no drugs in the Hhi class FDA approved, however IPI-926 and GDC-0449 are the 2 leading compounds in the class. IPI-926, GDC-0449, and LDE-225 are the only compounds that have generic names passed by the United States Adopted Name (USAN) council (Infinity IPI-926/saridegib, Genentech GDC-0449/vismodegib, and Novartis LDE-225/erismodegib). Although Infinity is further along in chondrosarcoma, myelofibrosis, and AML, Roche/Genentech recently submitted an NDA for GDC-0449 for the treatment of adults with advanced basal cell carcinoma (BCC) when surgery is no longer an option, and the FDA has accepted and has filed the NDA, giving it priority review status. Thus it appears that Roche/Genentech will be the first Hhi to market with GDC-0449, if approved, for the treatment of advanced BCC, with Infinity second to market with IPI-926 for treatment in chondrosarcoma. It appears Infinity will not pursue an indication for BCC and focus on cancers with high unmet needs.
Other Hhi-class compounds not as far along in development as IPI-926 and GDC-0449 include:
- Novartis' LDE-225 (USAN generic name erismodegib)
- Exelixis/Bristol-Myers Squibb's BMS-833923 (XL139)
- Millennium Pharmaceuticals's TAK-441
- Pfizer's PF-04449913
- "Pipeline: IPI-926". Infinity Pharmaceuticals.
- Tremblay, MR; Lescarbeau, A; Grogan, MJ; Tan, E; Lin, G; Austad, BC; Yu, LC; Behnke, ML; et al. (2009). "Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926)". Journal of Medicinal Chemistry. 52 (14): 4400–18. doi:10.1021/jm900305z. PMID 19522463.
- "Pipeline". Infinity Pharmaceuticals.
- "Genentech Pipeline". Genentech.
- "USAN Stem List" (PDF). AMA.
- "Names under consideration". AMA.
- "Search results for Hh clinical trials". United National Institute of Health's ClinicalTrials.gov.