916746-27-5Relevant articles and documents
Antibody–Drug Conjugates with Pyrrole-Based KSP Inhibitors as the Payload Class
Lerchen, Hans-Georg,Wittrock, Sven,Stelte-Ludwig, Beatrix,Sommer, Anette,Berndt, Sandra,Griebenow, Nils,Rebstock, Anne-Sophie,Johannes, Sarah,Cancho-Grande, Yolanda,Mahlert, Christoph,Greven, Simone,Terjung, Carsten
, p. 15243 - 15247 (2018)
The number of cytotoxic payload classes successfully employed in antibody–drug conjugates (ADCs) is still rather limited. The identification of ADC payloads with a novel mode of action will increase therapeutic options and potentially increase the therapeutic window. Herein, we describe the utilization of kinesin spindle protein inhibitors (KSPi) as a novel payload class providing highly potent ADCs against different targets, for instance HER-2 or TWEAKR/Fn14. Aspects of technical optimization include the development of different linker attachment sites, the stabilization of ADC linkage to avoid payload deconjugation and finally, the tailor-made design of active metabolites with a long lasting intracellular exposure in the tumor matching the mode of action of KSP inhibition. These KSPi-ADCs are highly potent and selective in vitro and demonstrate in vivo efficacy in a broad panel of tumor models including complete regressions in a patient-derived urothelial cancer model.
Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy
Wu, Chunlei,Cheng, Zhehong,Lu, Danyi,Liu, Ke,Cheng, Yulian,Wang, Pengxin,Zhou, Yimin,Li, Meiqing,Shao, Ximing,Li, Hongchang,Su, Wu,Fang, Lijing
, p. 991 - 1000 (2021/02/03)
Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.
DRUG ANTIBODY CONJUGATES
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Page/Page column 117-118, (2021/03/13)
Drug conjugates having formula [D-(X)b-(AA)w-(T)g-(L)-]n-Ab wherein: D is a drug moiety having the following formula (I) or a pharmaceutically acceptable salt or ester thereof, wherein D is covalently attached via a hydroxy group at OR1, OR3 or ZH, or a thiol group at ZH to (X)b if any, or (AA)w if any, or to (T)g if any, or (L); that are useful in the treatment of cancer.
DRUG ANTIBODY CONJUGATES
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Page/Page column 122-123, (2021/10/30)
Drug conjugates having formula [D-(X)b-(AA)w-(T)g-(L)-]n-Ab wherein: D is a drug moiety having the following formula (I) or a pharmaceutically acceptable salt, ester, solvate, tautomer or stereoisomer thereof, (
ANTIBODY DRUG CONJUGATES OF KINESIN SPINDEL PROTEIN (KSP) INHIBITORS WITH ANTIB7H3-ANTIBODIES
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, (2020/05/29)
The present application relates to novel binder drug conjugates (ADCs), to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for the treatment and/or prophylaxis of diseases and to the use of these ADCs for preparing medicaments for treatment and/or prophylaxis of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases. Such treatments can be effected as monotherapy or else in combination with other medicaments or further therapeutic measures.
ANTIBODY DRUG CONJUGATES COMPRISING ECTEINASCIDIN DERIVATIVES
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Page/Page column 227; 228, (2020/05/29)
Drug conjugates having formula [D-(X) b -(AA) w -(T) g -(L)-] n -Ab wherein: D is a drug moiety having the following formula (I) or a pharmaceutically acceptable salt, ester, solvate, tautomer or stereoisomer th
MAYTANSINOID DERIVATIVES, CONJUGATES THEREOF, AND METHODS OF USE
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Paragraph 0750; 0752, (2017/09/20)
Provided herein are maytansinoid compounds, derivatives thereof, conjugates thereof, and methods of treating or preventing proliferative diseases with the same.
ANTIBODY DRUG CONJUGATES
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Page/Page column 136, (2014/12/12)
Drug conjugates of formula [D-(X)b-(AA)w-(L)-]n-Ab wherein: D is a drug moiety having the following formula (I) or a pharmaceutically acceptable salt, ester, solvate, tautomer or stereoisomer thereof, wherein: A is selected from (II) and (III) R1, R2 and R3 is H, ORa, OCORa, OCOORa, alkyl, alkenyl, alkynyl, etc; R3' is, CORa, COORa, CONRaRb, etc; each of R4 to R10 and R12 is alkyl, alkenyl or alkynyl; R11 is H, CORa, COORa,alkyl, alkenyl or alkynyl, or R11 and R12+N+C atoms to which they are attached may form a heterocyclic group; each of R13 and R14 is H, CORa, COORa, alkyl, alkenyl or alkynyl; each Ra and Rb is H, alkyl, alkenyl, alkynyl, etc.; each dotted line represents an optional additional bond; X is an extending group; AA is an amino acid unit; L is a linker group; w is 0to 12; b is 0 or 1; A bis a moiety comprising at least one antigen binding site, and n is the ratio of the group [D-(X) b -(AA)w-(L)-] to the moiety comprising at least one antigen binding site and is in the range from 1 to 20, are useful in the treatment of cancer.
