Table 7.
Preclinical and clinical status of some kinase inhibitors, and bryostatin 1, with marine-derived natural product origins a,b.
| Compound Name (Trademark) | Target | Marine Source | Chemical Class | Company or Institution | Therapeutic Area | Status | References |
|---|---|---|---|---|---|---|---|
| plitidepsin (aplidin, 107) | VEGFR1 | ascidian | depsipeptide | PharmaMar | multiple myeloma | FDA-approved (2018) | [124,125,126,127] |
| midostaurin (108) | PKC-α, KIT, FLT3, VEGFR2, PDGFR-β | ascidian / bacteria | indolocarbazole | Novartis | acute myeloid leukemia, | FDA-approved (2017) | [124,127,128] |
| lestaurtinib (CEP-701, 109) | Flt-3, JAK-2 | ascidian / bacteria | indolocarbazole | Kyowa kirin | acute lymphoblast leukemia | Phase III | [127,130] |
| enzastaurin (LY317615, 110) | PKCβ, Class I PI3K | ascidian / bacteria | indolocarbazole | Eli Lilly | diffuse large B cell lymphoma | Phase III | [127,131] |
| kahalalide F (PM-92102, 111) | EGFR | mollusk and algae | tridecapeptide | PharmaMar Cephalon |
cancar | Phase II (terminated) | [127,132,133] |
| isokahalalide F (PM02734, elisidepsin, 112) | ErbB2 | mollusk and algae | tridecapeptide | PharmaMar | cancer | Phase I (terminated) | [14,124,127] |
| 7-hydroxystaurosporine (UCN-01, 113) | Chk2, PDPK1, Chk1 PKC | ascidian / bacteria | indolocarbazole | Kyowa kirin | cancer | Phase II (terminated) | [127,134,135,] |
| CEP-2563 (114, prodrug of CEP-751) | Trk-A, Trk-B, Trk-C | ascidian / bacteria | indolocarbazole | Cephalon | cancer | Phase I (terminated) | [14,124,127] |
| CEP-1347 (KT7515; 115) | MAP3K11 | ascidian | indolocarbazole | Teva | Parkinson’s | Phase III (terminated) | [14,124,127] |
| staurosporine (AM-2282, 116) | PKC, JAK2, CamKIII | ascidian / bacteria | indolocarbazole | Kyowa Hakko Kirin (originator) | multiple myeloma | Phase II (terminated) | [127,136] |
| bryostatin 1 b (117) | PKC | bryozoan | macrocytic lactone | Neurotrope Bioscience | Alzheimer’s | Phase II (terminated) | [127,137,138,139] |
a Staurosporine and several derivatives are included here. These compounds have been derived from terrestrial soil bacteria, ascidians and marine bacteria. b bryostatin 1 is a Protein Kinase C (PKC) activator.