MEDICINAL CHEMISTRY AT ITS BEST, Tracks information on drugs on worldwide basis by Dr Anthony Melvin Crasto, worlddrugtracker, helping millions with websites, 6 million hits on google, one lakh connections worldwide, email amcrasto@gmail.com, call +91 9323115463 India
Lutetium (177Lu) tezuvotide tetraxetan ($^{177}$Lu-rhPSMA-10.1) is an experimental radioligand therapy, developed by Bracco, that targets prostate-specific membrane antigen (PSMA) to treat metastatic castration-resistant prostate cancer. It uses a radiohybrid (rh) PSMA molecule, designed to have high binding affinity to PSMA-positive cancer cells and deliver targeted beta-minus radiation.
Key details:
Mechanism: It binds to PSMA-expressing cells, leading to DNA damage and tumor cell death.
Distinction: It is distinct from the FDA-approved ${177}$Lu-vipivotide tetraxetan (Pluvicto), though it is part of the same class of PSMA-targeted radiopharmaceutical agents.
Status: It has been tested in clinical trials as a potential therapy for advanced prostate cancer, including studies evaluating its efficacy and safety.
It is important to distinguish between the various PSMA-targeted agents, such as vipivotide tetraxetan, which is approved for use.
LutetiumLu 177 Tezuvotide Tetraxetan is a radioconjugate composed of PSMA-10.1, a prostate-specific membrane antigen (PSMA)-targeting ligand and radiolabeled with the beta-emitting radioisotope lutetiumLu 177 (177Lu), with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous administration, lutetiumLu 177 tezuvotide tetraxetan targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells as well as a variety of other solid tumors.
An open-label, multicentre, integrated Phase 1 & 2 study to evaluate the safety, tolerability, radiation dosimetry and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 injection in men with metastatic castrate-resistant prostate cancer
Luvometinib is an orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MAP2K, MAPK/ERK kinase, or MEK) 1 and 2, with potential antineoplastic activity. Upon administration, luvometinib selectively binds to and inhibits the activity of MEK1 and MEK2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway that regulates cell growth. This pathway is often dysregulated in a variety of tumor cell types through BRAF, KRAS and NRAS mutations.
Luvometinib is a small molecule drug. The usage of the INN stem '-tinib' in the name indicates that Luvometinib is a tyrosine kinase inhibitor. Luvometinib is under investigation in clinical trial NCT07004075 (FCN-159 Monotherapy Versus Chemotherapy by Investigator's Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration). Luvometinib has a monoisotopic molecular weight of 665.04 Da.
The title compound 8 was prepared following the same procedure as described for Example 5 by substituting methanesulfonyl chloride with cyclopropanesulfonyl chloride. MS-ESI (m/z): 666 [M + 1]+.
[0136] The title compound 8 was prepared following the same procedure as described for Example 5 by substituting methanesulfonyl chloride with cyclopropanesulfonyl chloride. MS-ESI (m/z): 666 [M + 1] +.
Looking for a Reliable SNAC Manufacturer? Let’s Talk.
At Blue Jet Healthcare Ltd, we specialize in the scalable, high-purity production of SNAC—a critical excipient powering the next generation of oral peptide therapeutics.
With increasing demand for SNAC across global pharma pipelines, choosing the right manufacturing partner is essential. Quality, timelines, and consistency matter.
Phone No. +91 (22) 22075307 / +91 (22) 22071691
Business Development/ Contract Manufacturing: marketing1@bluejethealthcare.com, madhu.gautam71@gmail.com
27 Sep 2022No development reported - Phase-II for Anxiety disorders in Russia (PO)
22 Dec 2020Chemical structure information added
22 Oct 2020Avineuro Pharmaceuticals and Avineuro Pharmaceuticals plans a phase III trial in Anxiety disorders in December 2020 (PO, Capsules) (NCT04598867)
MARITUPIRDINE is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
Ivachtchenko V, Ivanenkov Y (2013). "Small Molecule 5-HT6R Ligands: A Comprehensive Insight into their Selectivity and Activity". Current Bioactive Compounds. 9 (1): 64–100. doi:10.2174/1573407211309010007. ISSN1573-4072.
Benhamú B, Martín-Fontecha M, Vázquez-Villa H, Pardo L, López-Rodríguez ML (September 2014). "Serotonin 5-HT6 receptor antagonists for the treatment of cognitive deficiency in Alzheimer's disease". Journal of Medicinal Chemistry. 57 (17): 7160–81. doi:10.1021/jm5003952. PMID24850589.
Mevrometostat (development code PF-06821497) is an investigational anticancer drug that functions as a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2).[1][2] Currently under development by Pfizer, mevrometostat is being investigated primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in combination with enzalutamide.
PF-06821497 is under investigation in clinical trial NCT03460977 (PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma).
Mevrometostat is an orally available selective inhibitor of the histone lysine methyltransferase (HMT) enhancer of zeste homolog 2 (EZH2), with potential antineoplastic activity. Upon oral administration, mevrometostat selectively targets, binds to and inhibits the activity of EZH2. Inhibition of EZH2 specifically prevents the methylation of histone H3 on lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased proliferation of EZH2-expressing cancer cells. EZH2, an HMT class enzyme and the catalytic subunit of the polycomb repressive complex 2 (PRC2), is overexpressed or mutated in a variety of cancer cells and plays a key role in tumor cell proliferation; its expression is correlated with tumor initiation, progression, stem cell self-renewal, migration and angiogenesis.
MEVROMETOSTAT is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)- methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one (23a) and 5,8-dichloro-2-[(4- methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(S)-methoxy(oxetan-3-yl)methyl]- 3,4-dihydroisoquinolin-1(2H)-one (23b)
Multiple batches of (±)-5,8-dichloro-2-[(4-methoxy-6- methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[methoxy- (oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one 40 were combined (140 mg total), and the enantiomers separated by preparative chiral SFC [Column: (R,R)Whelk O1 250mm*30mm,5µ; mobile phase: EtOH; wavelength: 220 nm] to give, after lyophilization, 23a (50.3 mg, 36%) as a white solid, and 23b (22.8 mg, 16%) as a white solid. A small-molecule X-Ray crystal structure of 23a showed it to have absolute (R) stereochemistry. A small-molecule X-Ray crystal structure of 23b confirmed the expected absolute (S) stereochemistry. 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)- methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one (23a). After chiral SFC and lyophilization, 23a (50.3 mg, 36%) was obtained as a white solid. LCMS m/z 489 [M+Na]+; 1H NMR (400 MHz, CDCl3) δ 12.34 (br s, 1H), 7.49 (s, 1H), 5.93 (s, 1H), 5.05 (d, J=6.0 Hz, 1H), 4.78-4.61 (m, 6H), 3.88 (s, 3H), 3.50-3.48 (m, 2H), 3.38-3.37 (m, 1H), 3.31 (s, 3H), 2.94 (t, J=6.2 Hz, 2H), 2.35 (s, 3H). [α]D 22 +67.7° (c 0.1, MeOH); Chiral analysis: 100% ee; retention time 9.85 min; column (R,R)Whelk O1, 250×4.6mm I.D., 5µ; mobile phase 50% ethanol (0.05% DEA) in CO2; wavelength 220 nm. A crystalline sample of 23a was obtained by dissolving the lyophilized powder in hot isopropanol in a 1 dram vial, then letting the vial stand in a capped TLC chamber containing a layer of hexanes in the bottom, which allowed slow diffusion of hexanes into isopropanol. After two days, crystals (square plates) were collected. A smallmolecule X-Ray crystal structure of 23a showed it to have absolute (R) stereochemistry. Crystallographic data are available in the Supporting Information.
Mevrometostat is a small molecule inhibitor that targets EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2).[1][3] EZH2 plays a crucial role in epigenetic regulation by modifying gene expression patterns that control cellular fate decisions, including differentiation and self-renewal.[1]
In prostate cancer, EZH2 dysregulation contributes to treatment resistance through multiple pathways, including:
Promotion of neuroendocrine transdifferentiation[4]
Mevrometostat demonstrates dose-dependent EZH2 inhibition, leading to reactivation of tumor suppressor genes while suppressing genes involved in tumor progression.[5]
Clinical development
Phase I/II trials
The primary clinical evaluation of mevrometostat is being conducted through a phase 1/2 dose-expansion study (NCT03460977) investigating the combination of mevrometostat with enzalutamide and androgen deprivation therapy in patients with mCRPC.[6]
The dose-expansion portion of this study enrolled patients with mCRPC who had previously received abiraterone, with evidence of disease progression per modified Prostate Cancer Working Group 3 criteria.[2]
Key efficacy results
In the randomized dose-expansion study, the combination of mevrometostat (1,250 mg twice daily on an empty stomach) plus enzalutamide demonstrated:
49% relative reduction in the rate of progression or death
Approximately 8-month improvement in median radiographic progression-free survival (rPFS)
The median radiographic progression-free survival was 14.3 months with the combination therapy compared to 6.2 months with enzalutamide alone.[8]
Phase III trials
Based on promising phase I/II results, Pfizer has initiated multiple phase 3 clinical trials:
MEVPRO-1 study
The MEVPRO-1 study (NCT06551324) is a randomized phase 3 trial evaluating mevrometostat in combination with enzalutamide versus physician's choice of therapy in patients with mCRPC previously treated with abiraterone acetate.[9][10]
Study design: Randomized 1:1 to receive mevrometostat (875 mg twice daily with food) plus enzalutamide (160 mg daily) versus physician's choice of enzalutamide or docetaxel
Target enrollment: Approximately 600 patients
Primary endpoint: Blinded independent central review-assessed rPFS per RECIST 1.1 and PCWG3 criteria
The MEVPRO-2 study (NCT06629779) is evaluating mevrometostat plus enzalutamide in androgen receptor pathway inhibitor (ARPI)-naïve patients with mCRPC.[11][12]
Additional development
Pfizer has also initiated phase 3 trials evaluating mevrometostat plus enzalutamide in first-line metastatic castration-sensitive prostate cancer.[8][13]
Safety profile
The most common adverse events considered related to mevrometostat treatment include:
Dose optimization studies found that mevrometostat 875 mg twice daily with food showed similar efficacy and better safety compared to the 1,250 mg dose on an empty stomach.[15]
Pharmacokinetics
Based on safety and pharmacokinetic findings from phase 1 trials, mevrometostat 875 mg twice daily with food was selected as the recommended dose for phase 3 clinical development in combination with enzalutamide.[16]
Regulatory status
As of 2025, mevrometostat remains an investigational agent under clinical development by Pfizer. The drug has not received regulatory approval from the Food and Drug Administration (FDA), European Medicines Agency (EMA), or other regulatory authorities.
Schweizer MT, Calvo M, Moreno V, Mellado B, Castellano D, Spira AI, et al. (2025). "Mevrometostat (PF-06821497), an enhancer of zeste homolog 2 (EZH2) inhibitor, in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC): A randomized dose-expansion study". Journal of Clinical Oncology. 43 (5_suppl) LBA138. doi:10.1200/JCO.2025.43.5_suppl.LBA138.
Schweizer MT, Penkov K, Choudhury AD, Calvo E, Frank RC, Liu L, et al. (2024). "Phase 1 trial of mevrometostat (PF-06821497), a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2), in castration-resistant prostate cancer (CRPC)". Journal of Clinical Oncology. 42 (16_suppl): 5061. doi:10.1200/JCO.2024.42.16_suppl.5061.
Agarwal N, Schweizer MT, Castro E, Azad A, George DJ, Chakrabarti J, et al. (2025). "Mevrometostat (PF-06821497) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate: The phase 3, randomized MEVPRO-1 study". Journal of Clinical Oncology. 43 (5_suppl) TPS288. doi:10.1200/JCO.2025.43.5_suppl.TPS288.
