PHA-793887 is an intravenously-administered, inhibitor of cyclin dependent kinases CDK2, CDK5, CDK7, at IC50s of 8 nM, 5 nM, and 10 nM, respectively. [1] As a multi-CDK isoform inhibitor, it was postulated that PHA-793887 might overcome resistance-based mechanisms and lead to enhanced tumor suppression. PHA-793881 was found in Phase I dose-ranging studies to induce severe dose-related hepatotoxicity, thus halting clinical studies. [2]
Additionally, PHA-793887 was found to impair TLR signaling, thus suppressing cytokine production (type 1 interferon, interleukin-6, -10, -12, and TNFa), thereby increasing susceptibility of cancer patients to diseases such as herpes viridae. [3]
PHA-793887 was found to be an effective tool compound for the monitoring of the E2F gene signature pathway. [4]
Technical information:
| Chemical Formula: | C19H31N5O2 | |
| CAS #: | 718630-59-2 | |
| Molecular Weight: | 361.48 | |
| Purity: | >98% | |
| Appearance: | Off White | |
| Chemical Name: | N-(6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)-3-methylbutanamide | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | PHA-793887, PHA 793887, PHA793887 |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Brasca et al. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem, 2010, 18(5), 1844-1853. Pubmed ID: 20153204 |
| 2. | Massard et al., A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors. Cell Cycle 2011, 10(6), 963-970. Pubmed ID: 21368575 |
| 3. | Zoubir et al., An inhibitor of cyclin-dependent kinases suppresses TLR signaling and increases the susceptibility of cancer patients to herpesviridae. Cell Cycle 2011, 10(1), 118-126. Pubmed ID: 21200142 |
| 4. | Locatelli et al., Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin-dependent kinase inhibitor PHA-793887 in tumor and skin biopsies from a phase I clinical study. Mol. Cancer Ther. 2010, 9(5), 1265-1273 Pubmed ID: 21368575 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
