Abstract B066: Development of paired small-molecule drug conjugates for prostate cancer precision theranostics

2018 ◽  
Author(s):  
Bing Guan ◽  
Yunkou Wu ◽  
Jingyue Yang ◽  
Yahong Xiong ◽  
Jer-Tsong Hsieh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Small Molecule Drug ◽  
Drug Conjugates

scholarly journals Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2

2018 ◽  
Vol 24 (15) ◽  
pp. 3656-3667 ◽  
Author(s):  
Samuele Cazzamalli ◽  
Barbara Ziffels ◽  
Fontaine Widmayer ◽  
Patrizia Murer ◽  
Giovanni Pellegrini ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Small Molecule ◽  
Interleukin 2 ◽  
Carbonic Anhydrase Ix ◽  
Therapeutic Activity ◽  
Small Molecule Drug ◽  
Drug Conjugates

Phase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 2586-2586
Author(s):  
Michael J. Morris ◽  
Daniel Peter Petrylak ◽  
A. Oliver Sartor ◽  
Nicholas J. Vogelzang ◽  
Michael Groaning ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Drug Conjugate ◽  
Small Molecule Drug ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals Imaging Cellular Distribution of Bcl Inhibitors Using Small Molecule Drug Conjugates

2014 ◽  
Vol 25 (11) ◽  
pp. 2081-2085 ◽  
Author(s):  
Randy J. Giedt ◽  
Melissa M. Sprachman ◽  
Katherine S. Yang ◽  
Ralph Weissleder
Keyword(s):  
Small Molecule ◽  
Cellular Distribution ◽  
Small Molecule Drug ◽  
Drug Conjugates

scholarly journals Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 417
Author(s):  
Xinning Wang ◽  
Aditi Shirke ◽  
Ethan Walker ◽  
Rongcan Sun ◽  
Gopolakrishnan Ramamurthy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Targeted Delivery ◽  
Treatment Options ◽  
Maximum Tolerated Dose ◽  
In Vivo Studies ◽  
Castration Resistant Prostate Cancer ◽  
Drug Conjugates

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer. In this study, we explored the feasibility of targeted delivery of an antimitotic drug, monomethyl auristatin E (MMAE), to tumor tissue using a small-molecule based PSMA lig-and. With the aid of Cy5.5, we found that a cleavable linker is vital for the antitumor activity of the ligand–drug conjugate and have developed a new PSMA-targeting prodrug, PSMA-1-VcMMAE. In in vitro studies, PSMA-1-VcMMAE was 48-fold more potent in killing PSMA-positive PC3pip cells than killing PSMA-negative PC3flu cells. In in vivo studies, PSMA-1-VcMMAE significantly inhibited tumor growth leading to prolonged animal survival in different animal models, including metastatic prostate cancer models. Compared to anti-PSMA antibody-MMAE conjugate (PSMA-ADC) and MMAE, PSMA-1-VcMMAE had over a 10-fold improved maximum tolerated dose, resulting in improved therapeutic index. The small molecule–drug conjugates reported here can be easily synthesized and are more cost efficient than anti-body–drug conjugates. The therapeutic profile of the PSMA-1-VcMMAE encourages further clin-ical development for the treatment of advanced prostate cancer.

Phase 1 study of the PSMA-tubulysin small-molecule drug conjugate EC1169 in pts with metastatic castrate-resistant prostate cancer (mCRPC).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e13527-e13527 ◽  
Author(s):  
Samuel Ejadi ◽  
Nicholas J. Vogelzang ◽  
A. Oliver Sartor ◽  
Andrew Habbe ◽  
Binh Nguyen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Drug Conjugate ◽  
Small Molecule Drug ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant
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