-
International Journal of Pharmaceutics May 2001In-vitro studies were conducted to study the efficacy of mixed and self-emulsifying creams and hydrophobic ointment formulations in delivering peldesine (BCX-34) into...
In-vitro studies were conducted to study the efficacy of mixed and self-emulsifying creams and hydrophobic ointment formulations in delivering peldesine (BCX-34) into and across cryopreserved human cadaver skin (HCS). Oil-in-water cream formulations, containing 1% w/w of radiolabeled C(14) BCX-34 and propylene glycol (PG), glycerin (GLY), isopropyl myristate (IPM), oleic acid (OA) and capric-caprylic esters (CE) were prepared. Petrolatum and lanolin based ointments were also prepared with PG. Sections of the HCS, 250 microm thick, were fitted to vertical Franz diffusion chambers containing a receptor medium of pH 7.4 phosphate buffer solution maintained at 37 degrees C. Using the finite dose technique, 4-6 mg of a formulation sample was applied to the epidermal surface of each section and drug diffusion was permitted for 12 and 24 h periods. The distribution of drug into the HCS epidermis, dermis and into the receptor medium was measured by scintillation spectroscopy. The results show good correlation of the calculated in-vitro values for flux and skin-vehicle partition coefficients against the observed amounts of drug detected in the HCS. The mixed emulsion cream formulation containing PG delivered higher amounts of drug into the skin when compared to the same formulation containing GLY cream. The self-emulsifying cream formulation containing IPM had a higher skin-vehicle partition coefficient and delivered more drug into the dermis when compared to those formulations that contained OA and CE. The petrolatum ointment delivered six times more drug into the epidermis than the lanolin ointment, and had higher skin-vehicle partition values. In conclusion, creams containing PG and petrolatum-base formulations would be suitable for BCX-34 dermal delivery.
Topics: Algorithms; Caprylates; Dermatologic Agents; Diffusion; Emulsions; Excipients; Guanine; Humans; Immunosuppressive Agents; In Vitro Techniques; Myristates; Ointment Bases; Ointments; Propylene Glycols; Skin Absorption; Solubility
PubMed: 11337167
DOI: 10.1016/s0378-5173(01)00632-9 -
PDA Journal of Pharmaceutical Science... 1999Peldesine (BCX-34) is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP). The object of this study was to determine the preformulation parameters of...
Peldesine (BCX-34) is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP). The object of this study was to determine the preformulation parameters of BCX-34 and subsequently prepare a sterile liquid formulation for intravenous infusion. Ionization and solubility parameters were assessed prior to formulation development. Three pKa values of approximately 4.0, 5.2 and 10.3 were assigned for BCX-34. The pH-solubility profile showed an increase in solubility when the pH of the solution was less than the pKa1 value of 4.0 and when the pH was more than the pKa3 value of 10.3. BCX-34 has an octanol-water partition coefficient of approximately 7:1 (Log P = 0.8). The Van't Hoff temperature dependent solubility when measured over a range of 4-40 degrees C produced a heat of solution (delta Hc) of 7.68 kcal/mole. Based on these preformulation observations, two parenteral formulations containing 1 and 5 mg/mL of BCX-34 were prepared in an acidified saline solution and filled into 30 cc and 100 cc glass vials. Both formulation batches were sterile filtered, while only one 1 mg/mL batch was terminally autoclaved. The long-term stability of both solutions was performed and compared. Results of this study show that the drug product was stable. Following a screening study, Lactated Ringer's injection USP was selected as a suitable infusion medium for the dilution of the drug concentrate solutions.
Topics: Drug Compounding; Drug Stability; Guanine; Immunosuppressive Agents; Pharmaceutical Solutions; Sterilization
PubMed: 10754728
DOI: No ID Found -
The Cochrane Database of Systematic... Sep 2012Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time.
OBJECTIVES
To assess the effects of interventions for mycosis fungoides in all stages of the disease.
SEARCH METHODS
We searched the following databases up to January 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also checked reference lists of included studies for further references to relevant RCTs. We searched online trials registries for further references to unpublished trials and undertook a separate search for adverse effects of interventions for mycosis fungoides in non-RCTs in MEDLINE in May 2011.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for mycosis fungoides in people with any stage of the disease. At least 90% of participants in the trials must have been diagnosed with mycosis fungoides (Alibert-Bazin-type).
DATA COLLECTION AND ANALYSIS
Two authors independently assessed eligibility and methodological quality for each study and carried out data extraction. We resolved any disagreement by discussion. Primary outcomes were the impact on quality of life and the safety of interventions. When available, we reported on our secondary outcomes, which were the improvement or clearance of skin lesions, disease-free intervals, survival rates, relapse rates, and rare adverse effects. When possible, we combined homogeneous studies for meta-analysis. We used The Cochrane Collaboration's 'Risk of bias' tool to assess the internal validity of all included studies in six different domains.
MAIN RESULTS
The review included 14 RCTs involving 675 participants, covering a wide range of interventions. Eleven of the included trials assessed participants in clinical stages IA to IIB only (please see Table 1 for definitions of these stages).Internal validity was considerably low in studies with a high or unclear risk of bias. The main reasons for this were low methodological quality or missing data, even after we contacted the study authors, and a mean dropout rate of 26% (0% to 72%). Study size was generally small with a minimum of 4 and a maximum of 103 participants. Only one study provided a long enough follow-up for reliable survival analysis.Included studies assessed topical treatments, such as imiquimod, peldesine, hypericin, nitrogen mustard, as well as intralesional injections of interferon-α (IFN-α). The light therapies investigated included psoralen plus ultraviolet A light (PUVA), extracorporeal photopheresis (photochemotherapy), and visible light. Oral treatments included acitretin, bexarotene, and methotrexate. Treatment with parenteral systemic agents consisted of denileukin diftitox; a combination of chemotherapy and electron beam radiation; and intramuscular injections of active transfer factor. Nine studies evaluated therapies by using an active comparator; five were placebo-controlled RCTs.Twelve studies reported on common adverse effects, while only two assessed quality of life. None of these studies compared the health-related quality of life of participants undergoing different treatments. Most of the reported adverse effects were attributed to the interventions. Systemic treatments, and here in particular a combined therapeutic regimen of chemotherapy and electron beam, bexarotene, or denileukin diftitox, showed more adverse effects than topical or skin-directed treatments.In the included studies, clearance rates ranged from 0% to 83%, and improvement ranged from 0% to 88%. The meta-analysis combining the results of 2 trials comparing the effect of IFN-α and PUVA versus PUVA alone showed no significant difference in the relative risk of clearance: 1.07 (95% confidence interval 0.87 to 1.31). None of the included studies demonstrated a significant increase in disease-free intervals, relapse, or overall survival.
AUTHORS' CONCLUSIONS
This review identified trial evidence for a range of different topical and systemic interventions for mycosis fungoides. Because of substantial heterogeneity in design, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be established on the basis of the included RCTs. Taking into account the possible serious adverse effects and the limited availability of efficacy data, topical and skin-directed treatments are recommended first, especially in the early stages of disease. More aggressive therapeutic regimens may show improvement or clearance of lesions, but they also result in more adverse effects; therefore, they are to be considered with caution. Larger studies with comparable, clearly-defined end points for all stages of mycosis fungoides, and a focus on safety, quality of life, and duration of remission as part of the outcome measures, are necessary.
Topics: Antineoplastic Agents; Humans; Mycosis Fungoides; Neoplasm Staging; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 22972128
DOI: 10.1002/14651858.CD008946.pub2 -
Journal of Clinical Pharmacology Apr 2000The pharmacokinetic parameters of peldesine (BCX-34) were investigated after single and multiple oral doses in two groups of healthy adult volunteers. The... (Clinical Trial)
Clinical Trial
The pharmacokinetic parameters of peldesine (BCX-34) were investigated after single and multiple oral doses in two groups of healthy adult volunteers. The pharmacodynamic elevation of endogenous inosine and 2'-deoxyguanosine was simultaneously monitored. The first group of 8 subjects received an intravenous dose (18 mg/m2) and five oral doses (30, 63, 108, 144, and 192 mg/m2) of drug. A second group of 12 subjects received 160 mg/m2 in four and in six divided doses orally. Serial blood samples and total urine outputs were collected during dosing and for at least 24 hours after the last dose was administered. One set of samples was analyzed using high-pressure liquid chromatography/ultraviolet (LC/UV) methods, validated for intact drug in human plasma and urine samples. Another set of samples was analyzed for the biomarkers, inosine and 2'-deoxyguanosine, using high-pressure LC with either mass spectrometry (MS) or electrochemical detection (EC) methods. The pharmacokinetic parameters of inosine and 2'-deoxyguanosine were calculated using noncompartmental methods and correlated against the pharmacokinetic parameters of BCX-34. For the single-dose study, the results exhibited linear pharmacokinetics over the dose range from 30 to 144 mg/m2. The calculated terminal half-life was 3.5 +/- 1.0 h, and the absolute bioavailability of the oral formulation was approximately 51%. Analysis of urine in the first 24 hours of collection accounted for approximately 82% of the absorbed intact drug. Evaluation of the multiple-dose pharmacokinetics indicated that steady-state blood concentrations were achieved by 24 hours when the drug was administered four or six times a day. A drug dose-related elevation of plasma 2'-deoxyguanosine was observed. This phenomenon was not seen with plasma inosine levels. However, analysis of urine samples showed an increase in inosine output with an increase in the drug dose. The calculated terminal half-life of inosine and 2'-deoxyguanosine was 15.3 +/- 1.8 h and 1.3 +/- 0.1 h, respectively.
Topics: Administration, Oral; Adult; Area Under Curve; Capsules; Deoxyguanosine; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme Inhibitors; Female; Guanine; Humans; Inosine; Male; Middle Aged; Purine-Nucleoside Phosphorylase; Solutions; Time Factors
PubMed: 10761169
DOI: 10.1177/00912700022008991 -
Journal of the American Academy of... Jun 2001The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor.
OBJECTIVE
We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL).
METHODS
Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques.
RESULTS
Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677).
CONCLUSION
Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.
Topics: Administration, Cutaneous; Adult; Aged; Double-Blind Method; Enzyme Inhibitors; Female; Guanine; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Placebos; Treatment Outcome
PubMed: 11369904
DOI: 10.1067/mjd.2001.113478 -
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
Perspectives and challenges in developing small molecules targeting purine nucleoside phosphorylase.European Journal of Medicinal Chemistry May 2024As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions... (Review)
Review
As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions but also in immune system, including cell growth, apoptosis and cancer development and progression. Based on its T-cell targeting profile, PNP is a potential target for the treatment of some malignant T-cell proliferative cancers including lymphoma and leukemia, and some specific immunological diseases. Numerous small-molecule PNP inhibitors have been developed so far. However, only Peldesine, Forodesine and Ulodesine have entered clinical trials and exhibited some potential for the treatment of T-cell leukemia and gout. The most recent direction in PNP inhibitor development has been focused on PNP small-molecule inhibitors with better potency, selectivity, and pharmacokinetic property. In this perspective, considering the structure, biological functions, and disease relevance of PNP, we highlight the recent research progress in PNP small-molecule inhibitor development and discuss prospective strategies for designing additional PNP therapeutic agents.
Topics: Purine-Nucleoside Phosphorylase; Humans; Enzyme Inhibitors; Small Molecule Libraries; Molecular Structure; Animals; Antineoplastic Agents; Structure-Activity Relationship; Drug Development
PubMed: 38701712
DOI: 10.1016/j.ejmech.2024.116437 -
Current Pharmaceutical Design Jun 2000Purine nucleoside phosphorylase (PNP) is one of the enzymes comprising the purine salvage pathway , and is responsible for the catalysis of the reversible phosphorolytic... (Review)
Review
Purine nucleoside phosphorylase (PNP) is one of the enzymes comprising the purine salvage pathway , and is responsible for the catalysis of the reversible phosphorolytic cleavage of purine ribonucleosides and 2'-deoxyribonucleosides. The pivotal role of PNP in T-cell proliferation has been demonstrated in patients with inherited PNP deficiency, where T-cell levels may be 1-3% of normal. This observation helped establish the critical role of PNP in T-cells and provided a rationale for developing inhibitors of PNP. Inhibitors of PNP may be useful for treating a variety of T-cell related autoimmune diseases including psoriasis, rheumatoid arthritis and Crohn s disease and T-cell cancers. In this manuscript, the x-ray crystal structure of the PNP enzyme is described. Results of a structure-based drug design program aimed at designing small-molecule inhibitors of PNP are also described. Of the many classes of compounds synthesized, studied and reviewed, only one, the 3-pyridinylmethyl-9-deazaguanine (BCX-34, 39) analog has been used in clinical trials. Both topical and oral formulations of BCX-34 were studied in psoriatic patients and the results of these clinical trials are described.
Topics: Drug Design; Enzyme Inhibitors; Guanine; Humans; Models, Molecular; Psoriasis; Purine-Nucleoside Phosphorylase; Structure-Activity Relationship
PubMed: 10828318
DOI: 10.2174/1381612003400083 -
JAAD International Jun 2021Mycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists. (Review)
Review
BACKGROUND
Mycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists.
OBJECTIVE
The purpose of this study was to systematically review and assess the evidence on topical treatments for early-stage (IA, IB, IIA) MF.
METHODS
We performed a literature search via MEDLINE, Embase, Web of Science, and Cochrane databases. Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria were used to assess the certainty of the data.
RESULTS
Two searches yielded 1252 references; 26 met the inclusion criteria and included literature on nitrogen mustard, retinoids, corticosteroids, carmustine, fluorouracil, methotrexate-laurocapram, hexadecylphosphocholine, peldesine, ingenol mebutate, topical methotrexate with oxygen flow-assisted LP3 carrier, and resiquimod. Most studies were single intervention, observational series. Nitrogen mustard, with the most published reports, was effective with 12%-82% early-stage MF patients (total n > 1000) achieving complete remission (CR) (low certainty evidence). Clinical CR was achieved among 10%-60% treated with topical retinoids (low certainty evidence). Two moderate-sized retrospective case series on topical steroids had 18%-63% CR (low certainty evidence). Only single studies were available for the other therapies.
CONCLUSIONS
For most outcomes of interest, the GRADE certainty for topical therapies for early-stage MF was low. Further randomized controlled trials and inclusion of quality of life indicators are needed.
PubMed: 34409369
DOI: 10.1016/j.jdin.2021.01.002 -
European Journal of Medicinal Chemistry Feb 2023The present work describes a quinazolinone-based lead optimization for the development of novel purine nucleoside phosphorylase (PNP) inhibitors with quinazolinone...
Computational, in vitro and radiation-based in vivo studies on acetamide quinazolinone derivatives as new proposed purine nucleoside phosphorylase inhibitors for breast cancer.
The present work describes a quinazolinone-based lead optimization for the development of novel purine nucleoside phosphorylase (PNP) inhibitors with quinazolinone scaffold. Nineteen compounds were proposed and docked against PNP, the best 14 compounds with highest docking and affinity scores and low RMSD values were synthesized. Synthesis of new quinazolinone derivatives with variable acetamide substituents on two positions on quinazoline ring was performed. The structures assigned to the products were concordant with the microanalytical and spectral data. In vitro cytotoxicity on human breast cancer cell line (MCF7) was performed and identified compound 6g as the most potent with IC (0.99 ± 0.11 μM) which was further tested against five different breast cancer cell lines in addition to normal breast cell to determine the selectivity. Compound 6g was subjected to molecular dynamic simulation study, radiolabelling and biodistribution study to investigate its stability and selectivity toward breast cancers. The in vitro PNP inhibition results were aligned with the in silico, cytotoxicity, and biodistribution results where 6g showed the most potent PNP inhibitory activity with IC (0.159 ± 0.007 μM) when compared to Peldesine (BCX-34) IC (0.041 ± 0.002 μM).
Topics: Humans; Female; Purine-Nucleoside Phosphorylase; Breast Neoplasms; Quinazolinones; Tissue Distribution; Enzyme Inhibitors; Acetamides; Structure-Activity Relationship
PubMed: 36610250
DOI: 10.1016/j.ejmech.2023.115087