What is Cryptophcin analog?

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The cryptophycins are a group of cyanobacterial depsipeptides with a remarkable biological activity against multi-drug-resistant(MDR) cancer cells. As a potent class of cytotoxic agents the were evaluated as a payload for antibody drug conjugate payloads.

In various studies, free cryptophycin analog 1 has displayed cell activity in an order of magnitude more potent than payloads in approved antibody-drug conjugates, including Monomethyl Auristatine Eor MMAE and DM1.[1]


This potency increase was also reflected in the activity of the antibody-drug conjugate attached via a either cleavable or non-cleavable linker to cryptophycin. [1]

Mechanism of Action
Cryptophycins deplete microtubules through interaction with tubulin, thereby preventing cell division. They are capable of inducing apoptosis, possibly through other mechanisms in addition to that mediated by microtubule inhibition.

Cryptophycins were originally obtained from cyanobacteria. A synthetic analogue, known as cryptohycin-52 (LY355703), a novel antitubulin drug with in vitro and in vivo activity in non-small cell lung cancer has been investigated in clinical trials. Following promising phase I data, a multicenter phase II trial demonstrated disease stabilization in 40% of patients with platinum-resistant advanced ovarian cancer and non-small cell lung cancer (NSCLC). However, the development of the trial drug was discontinued because of lack of responses in patients with advanced NSCLC in spite of significant neurological toxicity. [2][3]


One of the major limitations in the use of microtubule-targeted agents, including cryptophycin, is the high rate of peripheral neurotoxicity, a major potentially dose-limiting side effect induced by these compounds. [4] Researchers have found that peripheral neuropathy is a limiting factor in the development of cryptophycin, leading to termination of the (pre-) clinical development of this agent.

While cryptophycin was considered extremely toxic and unacceptable to be used as chemotherapeutic drugs, new developments, including antibody-drug conjugates, have ‘resurrected’ the the potential use of this agent.

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ADC Review
ADC Review, Journal of Antibody-drug Conjugates (ISSN 2327-0152) launched in 2013, is designed to serve the needs of a diverse community of individuals including academia, life sciences, pharma, (basic, translational and clinical) research, clinicians/physicians, along with regulatory affairs, government authorities and representatives from payers, and policy makers. The Journal’s content includes peer reviewed research, commentaries, news features, discussions, editorials and blogs on topics relevant to a broad international readership. The Journal also offers a knowledge center (called ADC University) offering the latest and most relevant information about Antibody-drug Conjugates (ADCs), BiSpecific Antibodies, Site Specific Antibody Drug Conjugates, Small Molecule Drug Conjugates (SMDC), and Engineered Antibody Fragments. The purpose of the Journal is to present this information in an understandable and a useful format for all stakeholders.