Name: JUN68744
Brand: BOC Sciences
Price: 1999 USD
Availability: MadeToOrder

Synonyms

JUN-68744; JUN 68744; PSMA-617-linker; PSMA 617-linker; PSMA617-linker; Vipivotide tetraxetan Linker; (((S)-5-((S)-2-((1r,4S)-4-(aminomethyl)cyclohexane-1-carboxamido)-3-(naphthalen-2-yl)propanamido)-1-carboxypentyl)carbamoyl)-L-glutamic acid

IUPAC Name

(2S)-2-[[(1S)-5-[[(2S)-2-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-1-carboxypentyl]carbamoylamino]pentanedioic acid

Canonical SMILES

C1CC(CCC1CN)C(=O)NC(CC2=CC3=CC=CC=C3C=C2)C(=O)NCCCCC(C(=O)O)NC(=O)NC(CCC(=O)O)C(=O)O

InChI

InChI=1S/C33H45N5O9/c34-19-20-8-12-23(13-9-20)29(41)36-27(18-21-10-11-22-5-1-2-6-24(22)17-21)30(42)35-16-4-3-7-25(31(43)44)37-33(47)38-26(32(45)46)14-15-28(39)40/h1-2,5-6,10-11,17,20,23,25-27H,3-4,7-9,12-16,18-19,34H2,(H,35,42)(H,36,41)(H,39,40)(H,43,44)(H,45,46)(H2,37,38,47)/t20-,23-,25-,26-,27-/m0/s1

InChIKey

JHWCOTSIOATVKA-UIGMUVSQSA-N

Density

1.303±0.06 g/cm3 (Predicted)

Solubility

DMSO: 270 mg/ml (ultrasonic)

Appearance

Solid

Shipping

Room temperature

Storage

Store at -20°C

Boiling Point

1063.2±65.0°C (Predicted)

JUN68744 is a novel small molecule that has gained attention in the field of drug development, particularly in oncology. It is known for its ability to inhibit specific signaling pathways that are critical for cancer cell proliferation and survival. JUN68744 has shown promise as a targeted therapeutic agent, designed to block the activity of certain kinases or proteins involved in tumor growth. By interfering with these pathways, JUN68744 can potentially reduce tumor growth and metastasis, making it an attractive candidate for the treatment of various cancers, including those that are resistant to conventional therapies.

One of the key applications of JUN68744 is in the treatment of solid tumors, including lung, breast, and colorectal cancers. The compound works by inhibiting specific molecular targets that drive the growth and survival of cancer cells. For example, JUN68744 may target kinases involved in the regulation of cell cycle progression, apoptosis, or angiogenesis, which are often dysregulated in cancer. By modulating these pathways, JUN68744 has the potential to slow down or halt tumor progression, offering a new option for patients with cancers that are difficult to treat with standard chemotherapy or targeted therapies.

In addition to its use in solid tumors, JUN68744 is being explored for its potential to overcome drug resistance in cancer treatments. Many cancers develop resistance to traditional therapies over time, making them harder to treat effectively. JUN68744 may help to reverse or bypass some of these resistance mechanisms by targeting alternative pathways that cancer cells rely on for survival. This application could significantly enhance the efficacy of existing treatments and offer hope to patients with drug-resistant cancers, where few other options are available.

JUN68744 is also being investigated in combination therapy strategies. Researchers are exploring how this compound can be used alongside other cancer treatments, such as immune checkpoint inhibitors or other targeted agents, to enhance therapeutic outcomes. By combining JUN68744 with immunotherapy, for instance, it may help to sensitize tumors to immune attack, improving the overall effectiveness of the treatment. This approach could open up new avenues for more personalized and synergistic treatment regimens, improving patient outcomes in various types of cancer.

1.Clinical Translation and First In-Human Use of [(44)Sc]Sc-PSMA-617 for PET Imaging of Metastasized Castrate-Resistant Prostate Cancer

Eppard E, de la Fuente A, Benešová M, Khawar A, Bundschuh RA, Gärtner FC, Kreppel B, Kopka K, Essler M, Rösch F

BACKGROUND:Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications. In this context, the positron emitter scandium-44 is an attractive alternative for PET imaging. We report the synthesis of [44Sc]Sc-PSMA-617 as radiopharmaceutical with generator produced scandium-44, its in vitro characterization and clinical translation as part of a first in-human study.

2.Delayed response after repeated (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer

Rahbar K, Bögeman M, Yordanova A, Eveslage M, Schäfers M, Essler M, Ahmadzadehfar H

PURPOSE:Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA.METHODS:Seventy-one patients (median age: 72 years; range 44-87) received 3 cycles of RLT with Lu-PSMA (mean administered activity: 6.016 ± 0.543 GBq) every 8 weeks. Response was evaluated using serum PSA levels and a PSA decline ≥50% was considered as biochemical response. Additionally, any PSA decline after the first cycle was evaluated for further therapy effects after the second and third cycle.RESULTS:A total of 213 cycles were performed in 71 patients. Data for response and adverse events were available for all patients. A PSA decline ≥50% and some PSA decline occurred in 56% and 66% of the patients. Of 30 patients with a PSA response after the first cycle, 28 remained responders and 12/41 of non-responders responded to further therapy cycles.CONCLUSION:RLT with Lu-177-PSMA-617 shows respectable response rates. In this retrospective analysis, a relevant number of patients showed a delayed response, even if they did not respond to the first cycle of the therapy.

3.Predictors of overall survival in metastatic castration-resistant prostate cancer patients receiving [(177)Lu]Lu-PSMA-617 radioligand therapy

Ahmadzadehfar H, Schlolaut S, Fimmers R, Yordanova A, Hirzebruch S, Schlenkhoff C, Gaertner FC, Awang ZH, Hauser S, Essler M

Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis of and therapy for metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to measure overall-survival (OS) in mCRPC patients who received either abiraterone or enzalutamide prior to PSMA therapy. The second aim of this study was to analyse the predictors of OS according to different pre-therapeutic parameters and also the responses to the first cycle of radioligand therapy (RLT) base on PSA level. Patients with mCRPC and a history of therapy with either abiraterone or enzalutamide or both, were included in this study. Different laboratory tests and pre-therapeutic parameters have been included into the analysis. One-hundred patients received a total of 347 cycles of Lu-PSMA (median: three cycles). 69 patients showed a decline in PSA two months after the first cycle, and 38 of those patients showed a PSA decline of = > 50%. The median OS was 60 weeks. In the multivariate analysis, the level of albumin, AST and haemoglobin, existence of liver metastases and a decline of > 14% in PSA level had a significant impact on overall-survival. The median OS is significantly longer in patients without hepatic involvement, with high levels of albumin and Hb and low levels of AST. A decline in PSA levels of more than 14% was the most important response parameter with regard to overall survival.