VE-821 is a potent ATP-competitive inhibitor of ATR (Ki of 13nM). VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-dependent protein kinase (DNA-PK), mammalian target of rapamycin and phosphoinositol 3-kinase-γ (Ki s of 16 uM, 2.2 uM, >1 uM and 3.9 uM, respectively) and against a large panel of unrelated protein kinases. VE-821 has being shown to increase sensitivity of pancreatic cancer cells to radiation and chemotherapy.

COMPOUND401 is the reversible and selective inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) (IC50 values are 0.28 and 5.3 μM respectively). COMPOUND401 exhibits much reduced or no activity against 43 other commonly studied kinases, including PI 3-K, ATM, and ATR. Compound401 has been shown to induce apoptosis and inhibit FRAP-dependent growth in TSC1-/- murine embryo fibroblasts.

Apoptozole is an imidazole-based molecule, which induces apoptosis in cancer cells and can be investigated for cancer therapy. It was found, that apoptozole inhibits Heat shock proteins: Hsp70 and Hsc70. Further investigations have not found any experimental evidence that apoptozole interacts with HSP70 proteins in a specific and developable manner. Instead, was found, that apoptozole might form aggregates under aqueous conditions which could interact with HSP70 proteins in a non-specific manner, potentially leading to false positives and inconsistent data.

VER-50589 is an isoxazole compound that inhibits a heat shock protein Hsp90. Mean cellular antiproliferative GI(50) value for VER-50589 for a human cancer cell line panel were 78 nM/L, showing a 9-fold potency gain for the isoxazole. VER-50589 shows favorable pharmacokinetics and impairs tumor growth (colon cancer) in animal model. Glioblastoma cells do not acquire resistance to VER-50589 and resistance to other Hsp90 inhibitors does not produce cross-resistance to VER-50589.

AT7867 is a novel and potent inhibitor of both AKT and the downstream kinase p70 S6 kinase (p70S6K) and also of protein kinase A. This ATP-competitive small molecule potently inhibits both AKT and p70S6K activity at the cellular level, as measured by inhibition of GSK3beta and S6 ribosomal protein phosphorylation, and also causes growth inhibition in a range of human cancer cell lines as a single agent. AT7867 inhibited survival and proliferation of established (HT-29, HCT116 and DLD-1 lines) and primary human CRC cells. In vivo, intraperitoneal injection of AT7867 inhibited HT-29 xenograft tumor growth in nude mice. AKT activation was also inhibited in AT7867-treated HT-29 tumors. Together, the preclinical results suggest that AT7867 inhibits CRC cells via AKT-dependent and -independent mechanisms.

Staurosporine is an alkaloid isolated from the culture broth of Streptomyces staurosporesa. It exerts antimicrobial, hypotensive, and cytotoxic activity. The main biological activity of staurosporine is the inhibition of protein kinases through the prevention of ATP binding to the kinase. This is achieved through the stronger affinity of staurosporine to the ATP-binding site on the kinase. Staurosporine is a prototypical ATP-competitive kinase inhibitor in that it binds to many kinases with high affinity, though with little selectivity. It is a potent, cell permeable protein kinase C inhibitor with an IC50 of 0.7 nM. At higher concentration (1-20 nM), staurosporine also inhibits other kinases such as PKA, PKG, CAMKII and Myosin light chain kinase (MLCK). At 50-100 nM, it is a functional neurotrophin agonist, promoting neurite outgrowth in neuroblastoma, pheochromocytoma and brain primary neuronal cultures. At 0.2- 1 uM, staurosporine induces cell apoptosis. Staurosporine is also a potent GSK-3β inhibitor with a reported IC50 value of 15 nM. In research, staurosporine is used to induce apoptosis. It has been found that one way in which staurosporine induces apoptosis is by activating caspase-3. Staurosporine was discovered to have biological activities ranging from anti-fungal to anti-hypertensive. The interest in these activities resulted in a large investigative effort in chemistry and biology and the discovery of the potential for anti-cancer treatment. Staurosporine induces apoptosis by multiple pathways and that the inhibition of more than one kinase is responsible for its potent activity. Because the mechanism of action of staurosporine is distinct from traditional anticancer drugs, this may warrant further preclinical evaluations of the antitumor potential of new staurosporine derivatives either alone or in combination with death ligands or conventional chemotherapeutic drugs.

3-Amino-N-(2,6-difluorophenyl)-5-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide (CDK1/2 INHIBITOR III) is potent inhibitor of Cyclin-dependent kinase 1/2 (IC50=0.6nM and 0,5nM) with marked antiproliferative activity.

Indolocarbazole GO-6976 inhibited the calcium-dependent protein kinase C (PKC) isozymes alpha and beta 1. As PKC is a central enzyme that modulates numerous biological functions GO-6976 is extensively used as a tool for studying the involvement of PKC in signal transduction pathways. GO6976 was originally synthesized by Goedecke (formerly a subsidiary of Warner-Lambert, now Pfizer) in Germany. Preclinical investigations carried out by Goedecke have been for the potential treatment of HIV infections. Preclinical research with GO 6976 had been conducted by Biomol Inc. and Calbiochem in the USA as a potential treatment for cancer. No further information has been available for the compound therefore it is assumed that development has been discontinued. In addition to GO-6976 inhibition of PKC, it was reported that GO-6976 also inhibits JAK 2 and FLT3 tyrosine kinases and non-kinase transmembrane guanylyl cyclase.

Tubulysin A is a myxobacterial product that can function as an antiangiogenic agent in many in vitro assays. Tubulysin A is a novel antibiotic, which is anti-microtubule, anti-mitotic, apoptosis inducer, anticancer, anti-angiogenic, and antiproliferative. Tubulysins are cytotoxic peptides, which include 9 members (A-I). Tubulysin A has potential application as an anticancer agent. It arrests cells in the G2/M phase. Tubulysin A inhibits polymerization more efficiently than vinblastine and induces depolymerization of isolated microtubules. Tubulysin A has potent cytostatic effects on various tumor cell lines with IC50 in the picomolar range.

5F-DF-203-L-LYSINAMIDE (Phortress) is an experimental antitumor agent with potent and selective activity against human-derived carcinomas of breast, ovarian and renal origin. The mechanism of action of Phortress is distinct from all classes of chemotherapeutic agents currently in the clinic, and involves metabolic activation by cytochrome P450 (CYP) 1A1 to electrophilic species, which generate DNA adducts in sensitive tumors only. Phortress is in phase I clinical trials for the treatment of solid tumours. The compound was co-developed by Pharminox, University of Nottingham and Cancer Research UK.