SJG-136 (NSC 694501), A Novel Rationally Designed DNA Minor Groove Interstrand Cross-Linking Agent with Potent and Broad Spectrum Antitumor Activity

Alley, Michael C.; Hollingshead, Melinda G.; Pacula-Cox, Christine; Waud, William R.; Hartley, John A.; Howard, Philip W.; Gregson, Stephen J.; Thurston, David E.; Sausville, Edward A.

doi:10.1158/0008-5472.can-03-2942

Cited by 82 publications

(81 citation statements)

References 14 publications

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“…Activity was observed after a single bolus administration, although it gave the best efficacy after multiple administrations over a five‐day period 57. These encouraging results, coupled with data demonstrating a linear pharmacokinetic profile and differential cytotoxicity between leukaemia and bone marrow cells, led to the decision to evaluate SJG‐136 in Phase I clinical trials.…”

Section: Sjg‐136: the First Pbd Dimer To Undergo Clinical Evaluationmentioning

confidence: 97%

“…SJG‐136 failed to show activity in only one model (based on LOX IMVI) which was thought to be due to the mode of administration (i.e., s.c. rather than i.v. ),57 although the reasons for this are not fully understood.…”

Section: Sjg‐136: the First Pbd Dimer To Undergo Clinical Evaluationmentioning

confidence: 99%

“…Based on data from pre‐clinical toxicology studies in mice, rats and dogs,57, 88 it was initially administered as a 10 minute i.v. infusion every 21 days at a starting dose of 15 μg m −2 (i.e., 1/16 of the total dose given to dogs) which was doubled until drug‐related adverse events were observed.…”

Section: Sjg‐136: the First Pbd Dimer To Undergo Clinical Evaluationmentioning

confidence: 99%

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From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

et al. 2016

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The pyrrolo[2,1‐c][1,4]benzodiazepines (PBDs) are a family of sequence‐selective DNA minor‐groove binding agents that form a covalent aminal bond between their C11‐position and the C2‐NH2 groups of guanine bases. The first example of a PBD monomer, the natural product anthramycin, was discovered in the 1960s, and the best known PBD dimer, SJG‐136 (also known as SG2000, NSC 694501 or BN2629), was synthesized in the 1990s and has recently completed Phase II clinical trials in patients with leukaemia and ovarian cancer. More recently, PBD dimer analogues are being attached to tumor‐targeting antibodies to create antibody–drug conjugates (ADCs), a number of which are now in clinical trials, with many others in pre‐clinical development. This Review maps the development from anthramycin to the first PBD dimers, and then to PBD‐containing ADCs, and explores both structure–activity relationships (SARs) and the biology of PBDs, and the strategies for their use as payloads for ADCs.

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Section: Sjg‐136: the First Pbd Dimer To Undergo Clinical Evaluationmentioning

confidence: 97%

Section: Sjg‐136: the First Pbd Dimer To Undergo Clinical Evaluationmentioning

confidence: 99%

Section: Sjg‐136: the First Pbd Dimer To Undergo Clinical Evaluationmentioning

confidence: 99%

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From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

et al. 2016

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“…1B) which has been shown to reduce drastically the mass of 10 different xenografts (1). Phase I clinical trials of SJG-136, recently completed, showed positive results in the treatment of ovarian cancer (http://dtp.nci.nih.gov/timeline /noflash/success_stories/S7_SJG-136.htm).…”

mentioning

confidence: 99%

Cloning and Characterization of the Biosynthetic Gene Cluster for Tomaymycin, an SJG-136 Monomeric Analog

Chou

Khullar

et al. 2009

Appl Environ Microbiol

140

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“…Models were produced in the SYBYL modeling suite and images produced using UCSF Chimera. [94] www.intechopen.com…”

Section: Pbd Dimers and Trimersmentioning

confidence: 99%

Pyrrolobenzodiazepines as Sequence Selective DNA Binding Agents

Kamal¹,

Reddy²,

Srivastava³

et al. 2012

Medicinal Chemistry and Drug Design

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SJG-136 (NSC 694501), A Novel Rationally Designed DNA Minor Groove Interstrand Cross-Linking Agent with Potent and Broad Spectrum Antitumor Activity

Cited by 82 publications

References 14 publications

From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

Cloning and Characterization of the Biosynthetic Gene Cluster for Tomaymycin, an SJG-136 Monomeric Analog

Pyrrolobenzodiazepines as Sequence Selective DNA Binding Agents

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