Talazoparib (BMN 673) demonstrates excellent potency, inhibiting PARP1 and PARP2 enzyme activity. It inhibits PARP-mediated PARylation in a whole-cell assay and prevents proliferation of cancer cells carrying mutant BRCA1/2. Talazoparib is orally available, displaying favorable pharmacokinetic properties and remarkable antitumor efficacy in the BRCA1 mutant MX-1 breast cancer xenograft model following oral administration as a single-agent or in combination with chemotherapy agents such as temozolomide and cisplatin. Medivation (a subsidiary of Pfizer) is developing talazoparib (MDV 3800, formerly BMN 673 and LT 673) for the treatment of genetically defined cancers. On October 16, 2018, the FDA approved talazoparib (TALZENNA, Pfizer Inc.) for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2‑negative locally advanced or metastatic breast cancer.

CEP-33779 is a selective JAK2 inhibitor (IC50 of 1.8 nM) developed by Cephalon, Inc for treating autoimmune disease (rheumatoid arthritis, lupus nephritis) and cancer. CEP-33779 orally administrated with 55 mg/kg inhibits phosphorylation of STAT5 in HEL92 tumor extracts from HEL92 xenograft mice. CEP33779 orally administered twice daily at the dose of 55 mg/kg reduces mean paw edema and clinical scores in mice with collagen-antibody-induced arthritis (CAIA) or collagen-induced arthritis (CIA). CEP-33779 orally administered twice daily at the dose of 55 mg/kg totally inhibits paw phospho-STAT3 expression in CAIA or CIA mice, associated with decreased cytokines including IL-12, IFNγ, IL-2, IL-1β, TNFα, and GM-CSF. CEP33779 results in reduced bone degradation, reduced tissue destruction, and reduced osteoarthritis in a dose-dependent manner in CAIA or CIA mice. CEP33779 orally administrated at 100 mg/kg extends survival and reduces splenomegaly/lymphomegaly in MRL/lpr systemic lupus erythematosus mice, thus protect mice from developing glomerulonephritis. CEP-33779 orally administrated at 100 mg/kg decreases several SLE-associated proinflammatory cytokines and reduces levels of a bone resorption biomarker associated with increased osteoclast activity in MRL/lpr systemic lupus erythematosus mice. CEP33779 orally administered twice daily at the dose of 55 mg/kg induces regression of established colorectal tumors, reduces angiogenesis, and reduces proliferation of tumor cells in a mouse model of colitis-induced colorectal cancer. Tumor regression correlated with inhibition of STAT3 and NF-κB (RelA/p65) activation, and decreased the expression of proinflammatory, tumor-promoting cytokines interleukin (IL)-6 and IL-1β

Jervine (11-Ketocyclopamine) is a naturally occuring steroidal alkaloid is derived from the Veratrum plant species. Jervine is a teratogen implicated in birth defects when consumed by animals during a certain period of their gestation. Over the Hedgehog signaling pathway Jervine effectively inhibit the tumor growth using three human tumor xenograft models including lung cancer, pancreatic cancer and basal cell carcinoma. Jervine has the potential to advance to a treatment for different tumors.