A successful management of Candy Cane syndrome post Roux-en-Y gastric bypass: a rare case report.

Introduction and importance: Candy Cane syndrome (CCS) is a rare condition in which the proximal gastrojejunal attachment's afferent blind limb is elongated. This can lead to different symptoms, including nausea and vomiting, with less commonly described reflux and regurgitation symptoms. Case presentation: A 38-year-old female presented with a chronic complaint of postprandial pain, discomfort, and reflux lasting for about 2 years after a previous Roux-en-y gastric bypass (RYGB) surgery. Upper endoscopy was done and raised suspicion for CCS. The patient underwent an exploratory laparoscopy, which confirmed the diagnosis. Surgical resection of the afferent limb was done, and all symptoms were completely resolved at the postoperative follow-up. Clinical discussion: CCS is considered a rarely described complication that can occur after RYGB gastric bypass surgery. Diagnosing this condition includes performing upper gastrointestinal (GI) studies and endoscopy, which reveal a redundant afferent limb. Laparoscopy serves as a dual-purpose tool, confirming the diagnosis of CCS and providing a definitive curative intervention. Surgical resection has a high success rate, with evidence supporting its efficacy in relieving symptoms. Conclusion: As the popularity of Bariatric surgeries rises, it is crucial to consistently consider CCS, despite its rarity, as a potential complication. Although diagnosing CCS can be challenging, physicians should maintain a high index of suspicion, especially in patients presenting with upper GI symptoms following metabolic surgeries.

Pituitary apoplexy: a systematic review of non-gestational risk factors.

PURPOSE: Pregnancy is a known risk factor for Pituitary Apoplexy (PA) but there is a lack of consistency in the literature regarding non-gestational risk factors responsible for PA. METHODS: We did a systematic review following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify the non-gestational risk factors associated with the development of PA in adult patients with pituitary adenoma. Also, we discuss here a case of an elderly female with pituitary macroadenoma who was initially planned for pituitary resection electively but underwent emergency surgery after she developed PA. RESULTS: As per screening and eligibility criteria, seven studies with 4937 study participants were included in this systematic review out of which 490 (9.92%) patients had PA, including asymptomatic subclinical PA (SPA) and symptomatic clinical PA (CPA). The macroadenomas and negative staining of the tumor were found to be a significant risk factor consistently in multivariate analysis in three and two retrospective studies, respectively. However, the results were varied for any significant difference in the risk factors for apoplexy between SPA and CPA. Similarly, there was no consistency among the studies for risk factors significantly responsible for CPA or PA compared to controls. CONCLUSION: No single non-gestational risk factor is solely responsible for the development of PA in a pituitary adenoma compared to the control population. Tumor size (macroadenoma) and the non-functioning status of the adenoma are the only significant factors contributing independently toward an apoplectic event in most patients. Such patients can be prioritized for early pituitary tumor resection.

A potential protective role of congenital peritoneal encapsulation coexisting with metastatic colon cancer: a rare case report.

Introduction and importance: Congenital peritoneal encapsulation (CPE) is a rare condition in which the small intestine is encased within a mesothelial-lined sac. The following case is an extremely rare description of the co-existence of both colon cancer and peritoneal encapsulation, highlighting the potential role of this co-existence in preventing the spread of metastases and tumor implantation. Case-presentation: A 60-year-old female was diagnosed with metastatic colon cancer. During the operation, a thin fibrous membrane was found covering the small intestine, which suggested CPE. The tumor was removed, and the additional membrane was totally excised. The patient is currently receiving chemotherapy for metastatic treatment and is in good health. Clinical discussion: CPE is a medical condition that results from abnormal peritoneal development, and it is often confused with other differential diagnoses resulting from inflammatory causes. It can occur at different ages and remains asymptomatic for the majority of cases. However, it can be a potential cause of bowel obstruction. An intraoperative diagnosis can easily differentiate the case. The co-existence with colon cancer has been described only once in the literature. Conclusion: Peritoneal encapsulation is a rare, mostly asymptomatic condition. However, it may play a protective role in preventing metastatic colon cancer from affecting the small intestine, thus potentially opening up new avenues for the treatment of cancer metastases.

A massive primary hydatid splenic cyst was successfully managed through open total splenectomy: a case report and review article.

Background: Cystic echinococcosis (CE) is a parasitic infection that is caused by the tapeworm Echinococcus granulosus. CE is very common, especially in the rural areas of developing countries. The most commonly affected organs by hydatid cysts are the liver and the lungs. However, the primary splenic hydatid cyst (PSHC) is a very rare manifestation of CE with an incidence of 0.5-8%. Case presentation: A 17-year-old female patient presented with abdominal pain which gradually increased over months, along with anorexia and vomiting. Computerized tomography showed a massive splenic cystic mass. An open total splenectomy was performed. By follow-up, the platelet count and a postoperative chest X-ray were normal. The patient was prescribed Albendazole and analgesics. The pathological study confirmed the diagnosis of PSHC. Conclusion: Despite the occurrence of PSHC being very rare, it is very important to take it into consideration, especially in endemic areas.

A 20-year follow-up of successful surgical management for a complex case of pentalogy of fallot and dextrocardia with systemic and pulmonary venous anomalies: A rare case report.

INTRODUCTION AND IMPORTANCE: Pentaloy of fallot (POF) is a congenital cardiac anomaly that includes ventricular septal defect (VSD), pulmonary stenosis (PS), overriding of the aorta, and right ventricular hypertrophy. Dextrocardia, on the other hand, is a congenital condition in which the heart is right-sided. Rarely, both of these conditions can coexist. In this case, we report the 20-year follow-up results for the successful management of POF coexisting with Dextrocardia and other anomalies, which is the first described case in the literature. CASE PRESENTATION: A 3.5-year-old boy was admitted to the hospital with the main complaint of cyanosis and dyspnea. He was diagnosed with POF. Intraoperative inspection further revealed a Double outlet right ventricle (DORV), and other cardiac anomalies. Total repair surgery was successfully performed. Follow-up results showed a normal postoperative status with no abnormalities. Mild exertional dyspnea was noted after 20 years, but the patient is currently in good health. CLINICAL DISCUSSION: The coexistence of multiple congenital cardiac anomalies can make it challenging to be completely diagnosed, and for this purpose, different preoperative studies are recommended, like Echocardiography, cardiac catheterization, and Transabdominal echography. For the treatment of POF, pulmonary valve-sparing techniques have shown better long-term results, making them the preferred choice over other techniques. CONCLUSION: Very few cases reported the occurrence of Dextrocardia with POF and additional cardiac anomalies. Echocardiography and Transabdominal echography play a very important role in the preoperative diagnosis of such complex cases. Surgery is the standard treatment for these congenital malformations.

Evolution in the management of vestibular schwannoma: a single-center 15-year experience.

PURPOSE: To highlight the changes in the management of vestibular schwannoma (VS) since 2004 with a focus on small- to middle-size VS. METHODS: Retrospective analysis of the decisions made in skull base tumor board between 2004 and 2021. RESULTS: 1819 decisions were analyzed (average age 59.25, 54% females). Overall, 850 (47%) cases were allocated to a Wait and Scan (WS) approach, 416 (23%) received radiotherapy and 553 (30%) were treated surgically (MS). All stages considered WS increased from 39% before 2010 to 50% after 2010. Similarly, Stereotactic Radio Therapy (SRT) increased from 5 to 18%. MS decreased from 46 to 25%. It was more commonly proposed to younger patients and larger tumors, p < 0.001. For Koos stages 1, 2, and 3 there was a statistically significant increase in SRT, and a decrease in MS, p < 0.001. WS also increased for stages 1 and 2. However, such a trend was not observed for stage 3. MS remained the primary treatment modality for stage 4 tumors throughout the study period, p = 0.057. The significance of advanced age as a factor favoring SRT decreased over time. The opposite is true for serviceable hearing. There was also a decrease in the percentage of the justification "young age" in the MS category. CONCLUSION: The is a continuing trend towards non-surgical treatment. Small- to medium-sized VS witnessed an increase in both WS and SRT. There is only an increase in SRT for moderately large VS. Physicians are less and less considering young age as a factor favoring MS over SRT. There is a tendency towards favoring SRT when hearing is serviceable.

SAR439859, a Novel Selective Estrogen Receptor Degrader (SERD), Demonstrates Effective and Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models.

Primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy. However, substantial evidence indicates a continued role for ER signaling in tumor progression. Selective estrogen receptor degraders (SERD), such as fulvestrant, induce effective ER signaling inhibition, although clinical studies with fulvestrant report insufficient blockade of ER signaling, possibly due to suboptimal pharmaceutical properties. Furthermore, activating mutations in the ER have emerged as a resistance mechanism to current endocrine therapies. New oral SERDs with improved drug properties are under clinical investigation, but the biological profile that could translate to improved therapeutic benefit remains unclear. Here, we describe the discovery of SAR439859, a novel, orally bioavailable SERD with potent antagonist and degradation activities against both wild-type and mutant Y537S ER. Driven by its fluoropropyl pyrrolidinyl side chain, SAR439859 has demonstrated broader and superior ER antagonist and degrader activities across a large panel of ER+ cells, compared with other SERDs characterized by a cinnamic acid side chain, including improved inhibition of ER signaling and tumor cell growth. Similarly, in vivo treatment with SAR439859 demonstrated significant tumor regression in ER+ breast cancer models, including MCF7-ESR1 wild-type and mutant-Y537S mouse tumors, and HCI013, a patient-derived tamoxifen-resistant xenograft tumor. These findings indicate that SAR439859 may provide therapeutic benefit to patients with ER+ breast cancer, including those who have resistance to endocrine therapy with both wild-type and mutant ER.

Comparison of Postoperative Pain and Appetite in Pediatric Patients Undergoing Monopolar Tonsillotomy and Cold Steel Tonsillectomy.

OBJECTIVES: Adenotonsillectomy (AT) is amongst the most widely performed pediatric surgeries in the United States (US) and the whole world. AT includes two major surgical techniques: total tonsillectomy (TT) and partial tonsillectomy (PT). Several studies have been conducted to evaluate the difference between TT and PT and assess the comparative effectiveness, benefits, and sequelae between both. In Lebanon, very few studies were done tackling this issue and assessing its sequelae on the pediatric population. METHODS: A prospective study was conducted including pediatric patients aged between 2 and 9 years, who were admitted for partial tonsillectomy (PT) or total tonsillectomy (TT) in 2018. An estimated number of children included were 50: 25 patients underwent PT and 25 patients underwent TT. Patients were sent home on day 1 post-op with a questionnaire that evaluates the following over the first 10 days post-op: pain using the Wong-Baker Faces Pain Rating Scale and the "Parents Postoperative Pain Measure" (PPPM) questionnaire, and appetite using the visual analogue scale (VAS). RESULTS: Patients in the PT group and in the TT group had no demographical differences in terms of age, BMI, exposure to smoking, area of living, and attending a day care center. Comparison between PT and TT revealed a significant difference in both pain and appetite scales. Patients who underwent PT had significantly lower PPPM scores on the 1st, 2nd, 4th, 5th, 6th, and 10th day after surgery compared to the TT patients. Further validation was revealed by the Wong-Baker Faces Pain Rating Scale, showing that the PT surgery group experienced significantly less postoperative pain compared to the TT surgery group. Assessing the appetite using the visual analogue scale favored PT over TT. Comparisons revealed that most PT patients returned to their normal eating habits starting at day 4 while this was applicable in the TT group at day 10. Postoperative pain improved from day 1 to day 10 in both surgical groups. CONCLUSION: In conclusion, the recovery process after the PT surgery causes less postoperative morbidity, thus an earlier return to normal activity compared to the TT. The patients of the latter group are affected by more pain and less appetite over the first 10 days after the surgery.

Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer.

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy. However, fulvestrant shows poor pharmacokinetic properties in human, low solubility, weak permeation, and high metabolism, limiting its administration to inconvenient intramuscular injections. This Drug Annotation describes the identification and optimization of a new series of potent orally available SERDs, which led to the discovery of 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (43d), showing promising antitumor activity in breast cancer mice xenograft models and whose properties warranted clinical evaluation.

Efficacy and safety of sofosbuvir plus ribavirin for treatment of cirrhotic patients with genotype 4 hepatitis C virus in real-life clinical practice.

Egypt has the highest hepatitis C virus (HCV) prevalence in the world. Sofosbuvir is a new highly effective drug for treatment of HCV infection. Compared to previous treatments, sofosbuvir-based regimens provide a higher cure rate, fewer side effects, and a two- to fourfold reduced duration of therapy. The aim of this study was to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir plus ribavirin in Egyptian patients with liver cirrhosis due to chronic HCV infection. We studied 2400 cirrhotic Egyptian patients with chronic HCV infection who were treated with dual therapy with sofosbuvir and ribavirin for 24 weeks. Efficacy was determined by assessment of serum HCV RNA. Any adverse events during treatment were recorded. Two thousand four hundred cirrhotic Egyptian patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks were enrolled in the study. The mean age of the studied group (± SD) was 53.9 ± 6.5 years, 1549 (64.54%) were males, all were cirrhotic patients, 3.41% were treatment-experienced, the baseline mean HCV RNA concentration was 4.33 × 106 IU/mL, and 94.37% of the patients had completed the full course of therapy. The overall SVR12 rate was 71.2%. The most common adverse events were fatigue, myalgia, headache, insomnia, and anemia. One hundred thirty-five (5.63%) patients stopped treatment permanently due to the appearance of complications that prevented continuation of treatment. The sofosbuvir and ribavirin combination is safe and effective in treatment of HCV patients with liver cirrhosis. However, further studies are needed to establish the optimal treatment regimen for those cases.

Anti-Nuclear Cytoplasmic Antibody-Associated Vasculitis: A Probable Adverse Effect of Sofosbuvir Treatment in Chronic Hepatitis C Patients.

Background: Egypt has the largest hepatitis C virus (HCV) epidemic worldwide. Sofosbuvir is an antiviral drug acting by inhibition of the HCV NS5B polymerase. It has shown high efficacy in combination with several other drugs and has a low reported rate of side effects. Objective: The aim of this prospective cohort study was to assess the safety of sofosbuvir-based treatment regimens used to treat chronic hepatitis C infections and to detect any side effects of sofosbuvir not previously reported. Methods: We studied treatment side effects in 3,000 patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks or treated by pegylated interferon, sofosbuvir, and ribavirin triple therapy for 12 weeks. The endpoint of the study was the end of treatment. Results: Hyperbilirubinemia occurred frequently during treatment in both groups. Treatment was discontinued in 72 cases due to hepatic decompensation and drug complications; 8 of the cases had deep vein thrombosis (DVT) and 7 had cerebral ischemia. Surprisingly, 177/3,000 (5.9%) patients presented with abnormal bleeding, 85 of whom had a vasculitic skin rash. Conclusion: We report the occurrence of previously nonrecorded side effects with sofosbuvir, namely DVT and bleeding disorders associated with anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV).We believe this to be the first report of sofosbuvir-induced AAV skin lesions and bleeding disorders.

Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors.

Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives. Starting with hit compound 1a, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.

A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy.

Vps34 is a phosphoinositide 3-kinase (PI3K) class III isoform that has attracted major attention over the recent years because of its role in autophagy. Herein we describe the biological characterization of SAR405, which is a low-molecular-mass kinase inhibitor of Vps34 (KD 1.5 nM). This compound has an exquisite protein and lipid kinase selectivity profile that is explained by its unique binding mode and molecular interactions within the ATP binding cleft of human Vps34. To the best of our knowledge, this is the first potent and specific Vps34 inhibitor described so far. Our results demonstrate that inhibition of Vps34 kinase activity by SAR405 affects both late endosome-lysosome compartments and prevents autophagy. Moreover, we show that the concomitant inhibition of Vps34 and mTOR, with SAR405 and the US Food and Drug Administration-approved mTOR inhibitor everolimus, results in synergistic antiproliferative activity in renal tumor cell lines, indicating a potential clinical application in cancer.

Discovery and optimization of pyrimidone indoline amide PI3Kß inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers.

Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3Kß in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3Kß-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (7) and the optimization of this new series of active and selective pyrimidone indoline amide PI3Kß inhibitors. 2-[2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (28), identified following a carefully designed methyl scan, displayed improved physicochemical and in vitro pharmacokinetic properties. Structural biology efforts enabled the acquisition of the first X-ray cocrystal structure of p110ß with the selective inhibitor compound 28 bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure-activity relationship for the series. Compound 28 demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclinical investigation. Following successful development, compound 28 entered phase I/Ib clinical trial in patients with advanced cancer.

Preparation and optimization of new 4-(morpholin-4-yl)-(6-oxo-1,6-dihydropyrimidin-2-yl)amide derivatives as PI3Kß inhibitors.

From a HTS campaign, a new series of pyrimidone anilides exemplified by compound 1 has been identified with good inhibitory activity for the PI3Kß isoform. The structure of compound 1 in PI3Kγ was solved revealing a binding mode in agreement with the SAR observed on PI3Kß. These compounds displayed inhibition in the nanomolar range in the biochemical assay and were also potent p-Akt inhibitors in a PTEN-deficient PC3 prostate cancer cell line. Optimization of in vitro pharmocokinetic properties led to compound 25 exhibiting 52% bioavailability in mice and target engagement in an acute PK/PD study.

Discovery and optimization of new benzimidazole- and benzoxazole-pyrimidone selective PI3Kß inhibitors for the treatment of phosphatase and TENsin homologue (PTEN)-deficient cancers.

Most of the phosphoinositide-3 kinase (PI3K) kinase inhibitors currently in clinical trials for cancer treatment exhibit pan PI3K isoform profiles. Single PI3K isoforms differentially control tumorigenesis, and PI3Kß has emerged as the isoform involved in the tumorigenicity of PTEN-deficient tumors. Herein we describe the discovery and optimization of a new series of benzimidazole- and benzoxazole-pyrimidones as small molecular mass PI3Kß-selective inhibitors. Starting with compound 5 obtained from a one-pot reaction via a novel intermediate 1, medicinal chemistry optimization led to the discovery of compound 8, which showed a significant activity and selectivity for PI3Kß and adequate in vitro pharmacokinetic properties. The X-ray costructure of compound 8 in PI3Kδ showed key interactions and structural features supporting the observed PI3Kß isoform selectivity. Compound 8 achieved sustained target modulation and tumor growth delay at well tolerated doses when administered orally to SCID mice implanted with PTEN-deficient human tumor xenografts.

Role of statins in the treatment of chronic hepatitis C virus infection.

This study assessed the clinical outcome of fluvastatin in addition to the standard regimen used now for treatment of chronic HCV in Egypt. A total of 80 patients with chronic hepatitis C virus infection fulfilled clinical, laboratory and histo-pathological criteria were ready for interferon therapy. They were divided into two groups: GI (N = 40) received standard treatment for HCV (Pegylated interferon and Ribavirin) and GII (N = 40) received standard treatment plus Fluvastatin (80 mg/daily). Six months before and after treatment liver function tests and HCV-RNA were evaluated. The results showed that addition of Fluvastatin to the standard HCV treatment (Pegylated interferon and Ribavirin) significantly increased sustained virological response (SVR) from (55%-62.5%; P < 0.01) and significantly decreased viral load in relapse patients (P < 0.001). No significant differences and correlations were found between serum levels of LDL-cholesterol and viral load before and after treatment in both groups.

Thyroid function in patients with chronic hepatitis C virus infection under interferon therapy.

The study examined 60 HCV patients with normal baseline levels of TSH. The patients received subcutaneous pegylated interferon a-2b weekly in addition to oral ribavirin. Before the start of the interferon therapy, serum TSH, thyroglobulin-Ab (TG-Ab) and antiperoxidase antibodies (TPO-Ab) were measured. Three months after interferon therapy serum levels of TSH were measured to all patients; patients with abnormal TSH were subjected to the measurements of FT3, FT4, TPO-Ab, TG-Ab, and thyroid stimulating immunoglobulin levels (TSI). After 3 months of therapy, 48 patients (80%) had normal TSH, and 12 patients (20%) had abnormal TSH. Of 12 patients with abnormal TSH 10 (16.6%) had high levels of TSH (hypothyroidism), while the other two (3.4%) had low levels of TSH (Hyperthyroidism). Of 10 patients with hypothyroidisms, 6 patients (10%) had overt hypothyroidism and 4 patients (6.6%) had subclinical hypothyroidism. All patients with abnormal TSH had significant higher levels of TG-Ab, TPO-Ab and TSI (in cases with hyperthyroidism only) than the patients with normal levels of TSH (p < 0.001), the levels of TPO-Ab only of the most patients with abnormal TSH were above the normal reference range before the start of interferon therapy. Patients with hyperthyroidism, one was presented by clinical picture of overt hyperthyroidism, and the second by subclinical hyperthyroidism. All patients with overt hypo and hyperthyroidism received medical treatment, with normalization of levels of TSH and improvement of clinical symptoms and completed their course of interferon therapy Forty patients (66.6%) responded to interferon (-ve PCR for HCV), while 20 (33.3%) did not respond, 5 had TSH abnormalities that were significantly higher than those in patient with normal TSH {5/12 (41.6%).versus 15/48 (31%); p < 0.01}.

Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: advantages in comparison with competitive inhibitors.

A new series of IGF-1R inhibitors related to hydantoins were identified from a lead originating from HTS. Their noncompetitive property as well as their slow binding characteristics provided a series of compounds with unique selectivity and excellent cellular activities.