https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

http://caprockhematology.com/Site/AML_and_ALL_files/AML%20Review%20Blood%202010.pdf

Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet.

Although traditionally natural products have played an important role in drug discovery, in the past few years most Big Pharma companies have either terminated or considerably scaled down their natural product operations. This is despite a significant number of natural product-derived drugs being ranked in the top 35 worldwide selling ethical drugs in 2000, 2001, and 2002. There were 15 new natural product-derived drugs launched from 2000 to 2003, as well as 15 natural product-derived compounds in Phase III clinical trials or registration at the end of 2003. Recently, there has been a renewed interest in natural product research due to the failure of alternative drug discovery methods to deliver many lead compounds in key therapeutic areas such as immunosuppression, anti-infectives, and metabolic diseases. To continue to be competitive with other drug discovery methods, natural product research needs to continually improve the speed of the screening, isolation, and structure elucidation processes, as well addressing the suitability of screens for natural product extracts and dealing with issues involved with large-scale compound supply.

/pdf/the-role-of-natural-product-chemistry-in-drug-discovery-32f4bde9v3.pdf

The Role of Natural Product Chemistry in Drug Discovery

Natural products have inspired chemists and physicians for millennia. Their rich structural diversity and complexity has prompted synthetic chemists to produce them in the laboratory, often with therapeutic applications in mind, and many drugs used today are natural products or natural-product derivatives. Recent years have seen considerable advances in our understanding of natural-product biosynthesis. Coupled with improvements in approaches for natural-product isolation, characterization and synthesis, these could be opening the door to a new era in the investigation of natural products in academia and industry.

Lessons from natural molecules

BackgroundThe prognosis for adults with relapsed acute lymphoblastic leukemia is poor. We sought to determine whether inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, results in better outcomes in patients with relapsed or refractory acute lymphoblastic leukemia than does standard therapy. MethodsIn this phase 3 trial, we randomly assigned adults with relapsed or refractory acute lymphoblastic leukemia to receive either inotuzumab ozogamicin (inotuzumab ozogamicin group) or standard intensive chemotherapy (standard-therapy group). The primary end points were complete remission (including complete remission with incomplete hematologic recovery) and overall survival. ResultsOf the 326 patients who underwent randomization, the first 218 (109 in each group) were included in the primary intention-to-treat analysis of complete remission. The rate of complete remission was significantly higher in the inotuzumab ozogamicin group than in the standard-therapy group (80.7% [95% confidence in...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1509277

Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia.

Calicheamicin gamma 1I is a recently discovered diyne-ene--containing antitumor antibiotic with considerable potency against murine tumors. In vitro, this drug interacts with double-helical DNA in the minor groove and causes site-specific double-stranded cleavage. It is proposed that the observed cleavage specificity is a result of a unique fit of the drug and DNA followed by the generation of a nondiffusible 1,4-dehydrobenzene--diradical species that initiates oxidative strand scission by hydrogen abstraction on the deoxyribose ring. The ability of calicheamicin gamma 1I to cause double-strand cuts at very low concentrations may account for its potent antitumor activity.

https://science.sciencemag.org/content/sci/240/4856/1198.full.pdf

Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically

Calichemicins, a novel family of antitumor antibiotics. 2. Chemistry and structure of calichemicin .gamma.1I

This disclosure describes disulfide analogs of the family of antibacterial and antitumor agents known collectively as the LL-E33288 complex.

Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group

This disclosure describes a method for constructing targeting agent drug conjugates from the family of methyltrithio antibacterial and antitumor agents.

Process for preparing targeted forms of methyltrithio antitumor agents

This disclosure describes a method for constructing carrier-drug conjugates from the family of methyltrithio antibacterial and antitumor agents.

William J. McGahren

Papers

Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically

Calichemicins, a novel family of antitumor antibiotics. 2. Chemistry and structure of calichemicin .gamma.1I

Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group

Process for preparing targeted forms of methyltrithio antitumor agents

Targeted forms of methyltrithio antitumor agents