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Article: Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing.

Malla, RamaRao / Viswanathan, Sathiyapriya / Makena, Sree / Kapoor, Shruti / Verma, Deepak / Raju, Alluri Ashok / Dunna, Manikantha / Muniraj, Nethaji

Cancers

2024 Volume 16, Issue 8

Abstract: Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens ... ...

Abstract	Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence of drug resistance further complicates therapeutic efficacy, underscoring the urgent need for alternative approaches. Drug repurposing, characterized by the utilization of existing drugs for novel clinical applications, emerges as a promising avenue for addressing these challenges. Repurposed drugs, comprising FDA-approved (in other disease indications), generic, off-patent, and failed medications, offer distinct advantages including established safety profiles, cost-effectiveness, and expedited development timelines compared to novel drug discovery processes. Various methodologies, such as knowledge-based analyses, drug-centric strategies, and computational approaches, play pivotal roles in identifying potential candidates for repurposing. However, despite the promise of repurposed drugs, drug repositioning confronts formidable obstacles. Patenting issues, financial constraints associated with conducting extensive clinical trials, and the necessity for combination therapies to overcome the limitations of monotherapy pose significant challenges. This review provides an in-depth exploration of drug repurposing, covering a diverse array of approaches including experimental, re-engineering protein, nanotechnology, and computational methods. Each of these avenues presents distinct opportunities and obstacles in the pursuit of identifying novel clinical uses for established drugs. By examining the multifaceted landscape of drug repurposing, this review aims to offer comprehensive insights into its potential to transform cancer therapeutics.
Language	English
Publishing date	2024-04-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16081463
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Article ; Online: Design & development of customizable web API for interoperability of antimicrobial resistance data.

Kaur, Jasleen / Kaur, Jasmine / Kapoor, Shruti / Singh, Harpreet

Scientific reports

2021 Volume 11, Issue 1, Page(s) 11226

Abstract: Antimicrobial resistance (AMR) is a global health emergency. Complementary to developing new drugs, AMR can be monitored and controlled through cost-effective active surveillance of resistance. As an initiative to monitor resistance, countries all across ...

Abstract	Antimicrobial resistance (AMR) is a global health emergency. Complementary to developing new drugs, AMR can be monitored and controlled through cost-effective active surveillance of resistance. As an initiative to monitor resistance, countries all across the globe are collecting data using a variety of surveillance tools. Moreover, hospitals routinely collect the AMR data for treatment which is being stored in their Laboratory and Hospital Information systems (LIS-HIS). The generated clinical data is collected & stored in various formats, making it very difficult to analyze and generate national reports. To integrate the stored clinical data for predictive modeling and analysis, there is an immediate need for a one-stop data repository capable of importing and exporting data in simple data exchange formats (CSV/Excel). The paper highlights the design & development of i-DIA, a python-based web API to facilitate the interoperability of AMR data by automatically importing the bulk of medical data from CSV files into generic data management and analysis system. The i-DIA has been integrated and tested with the ICMR's AMR surveillance network on in-house developed software, i-AMRSS. The i-AMRSS is presently collecting data from 31 laboratories across India and i-DIA has been used to import data generated from LIS & HIS of a few hospitals directly into the system. The paper also proposes the complete web-based framework (an extension of i-DIA) integrated with peer-to-peer system architecture.
MeSH term(s)	Anti-Bacterial Agents ; Drug Resistance, Bacterial ; Epidemiological Monitoring ; Humans ; Internet ; Software
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-05-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-90601-z
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Article ; Online: Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents.

Hoch, Matthias / Huth, Felix / Sato, Masahiko / Sengupta, Tirtha / Quinlan, Michelle / Dodd, Stephanie / Kapoor, Shruti / Hourcade-Potelleret, Florence

Clinical and translational science

2022 Volume 15, Issue 7, Page(s) 1698–1712

Abstract: Asciminib is a first-in-class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. Asciminib is a substrate of CYP3A4 and P-glycoprotein (P-gp) and possesses pH-dependent solubility in aqueous solution. This report summarizes the ... ...

Abstract	Asciminib is a first-in-class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. Asciminib is a substrate of CYP3A4 and P-glycoprotein (P-gp) and possesses pH-dependent solubility in aqueous solution. This report summarizes the results of two phase I studies in healthy subjects aimed at assessing the impact of CYP3A and P-gp inhibitors, CYP3A inducers and acid-reducing agents (ARAs) on the pharmacokinetics (PK) of asciminib (single dose of 40 mg). Asciminib exposure (area under the curve [AUC]) unexpectedly decreased by ~40% when administered concomitantly with the strong CYP3A inhibitor itraconazole oral solution, whereas maximum plasma concentration (C
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Cyclodextrins ; Cytochrome P-450 CYP3A/metabolism ; Cytochrome P-450 CYP3A Inducers/pharmacokinetics ; Cytochrome P-450 CYP3A Inhibitors/pharmacology ; Drug Interactions ; Healthy Volunteers ; Humans ; Itraconazole/pharmacology ; Niacinamide/analogs & derivatives ; Pyrazoles ; Reducing Agents
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Cyclodextrins ; Cytochrome P-450 CYP3A Inducers ; Cytochrome P-450 CYP3A Inhibitors ; Pyrazoles ; Reducing Agents ; asciminib ; Niacinamide (25X51I8RD4) ; Itraconazole (304NUG5GF4) ; Cytochrome P-450 CYP3A (EC 1.14.14.1)
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.13285
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Article ; Online: Cervical epidural blood patch--A literature review.

Kapoor, Shruti G / Ahmed, Shihab

Pain medicine (Malden, Mass.)

2015 Volume 16, Issue 10, Page(s) 1897–1904

Abstract: Objective: Epidural blood patches (EBP) are rarely performed at the cervical levels, primarily due to fear of neurological complications such as spinal cord compression. We reviewed the literature to provide an evidence-based review of performance of ... ...

Abstract	Objective: Epidural blood patches (EBP) are rarely performed at the cervical levels, primarily due to fear of neurological complications such as spinal cord compression. We reviewed the literature to provide an evidence-based review of performance of cervical EBPs, with a specific focus on indication, technique, safety, and efficacy. Design: A comprehensive electronic literature search was done to include studies that reported on performance of cervical EBPs in patients with CSF leak at the cervical level. Data regarding indication, level of CSF leak, level of cervical EBP, volume of blood used, efficacy, and complications were collected. Results: A total of 15 studies, reporting on 19 patients were included. All patients presented with a headache that increased in the standing position, and improved in the supine position. All patients were identified to have a CSF leak at the cervical level. Eight patients first underwent a lumbar EBP, without complete, long-term relief. All these patients, along with 11 patients who did not undergo a lumbar EPB prior to cervical EBP, reported complete, long-term pain relief. EBPs were mostly done in the prone position, using imaging guidance. An average of 5-8 mL of autologous blood was injected in the epidural space. No major neurological complications were reported in any patient. Conclusion: The review suggests that cervical EBP can be performed for cervical CSF leaks associated with positional headache without a significant risk of serious adverse events. Classification of evidence: Our review provides Class II level of evidence that cervical EBPs are safe and effective in reliving positional headache due to CSF leak.
MeSH term(s)	Adult ; Blood Patch, Epidural/statistics & numerical data ; Causality ; Cerebrospinal Fluid Leak/epidemiology ; Cerebrospinal Fluid Leak/therapy ; Cervical Vertebrae ; Comorbidity ; Evidence-Based Medicine ; Female ; Headache/epidemiology ; Headache/prevention & control ; Humans ; Incidence ; Male ; Middle Aged ; Pain Measurement/statistics & numerical data ; Postoperative Complications/epidemiology ; Postoperative Complications/therapy ; Risk Assessment ; Spinal Puncture/statistics & numerical data ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	2015903-1
ISSN	1526-4637 ; 1526-2375
ISSN (online)	1526-4637
ISSN	1526-2375
DOI	10.1111/pme.12793
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Article ; Online: Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.

Verma, Deepak / Kapoor, Shruti / Kumari, Sarita / Sharma, Disha / Singh, Jay / Benjamin, Mercilena / Bakhshi, Sameer / Seth, Rachna / Nayak, Baibaswata / Sharma, Atul / Pramanik, Raja / Palanichamy, Jayanth Kumar / Sivasubbu, Sridhar / Scaria, Vinod / Arora, Mohit / Kumar, Rajive / Chopra, Anita

PNAS nexus

2024 Volume 3, Issue 2, Page(s) pgae011

Abstract: T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on ... ...

Abstract	T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes-
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgae011
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Article: On the exact transient solution of fluid queue driven by a birth death process with specific rational rates and absorption

Kapoor, Shruti / Selvamuthu, Dharmaraja

Opsearch : journal of the Operational Research Society of India Vol. 52, No. 4 , p. 746-755

2015 Volume 52, Issue 4, Page(s) 746–755

Author's details	Shruti Kapoor, Dharmaraja Selvamuthu
Keywords	Fluid queue ; Birth death process ; Continued fraction
Language	English
Publisher	OperationalResearch Society of India
Publishing place	New Delhi
Document type	Article
ZDB-ID	417088x ; 2516085-0
ISSN	0975-0320 ; 0030-3887
ISSN (online)	0975-0320
ISSN	0030-3887
Database	ECONomics Information System

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Article ; Online: Pharmacokinetics of capmatinib in participants with hepatic impairment: A phase 1, open-label, single-dose, parallel-group study.

Chen, Xinhui / Cui, Xiaoming / Pognan, Nathalie / Quinlan, Michelle / Kapoor, Shruti / Rahmanzadeh, Gholamreza / Giovannini, Monica / Marbury, Thomas C

British journal of clinical pharmacology

2021 Volume 88, Issue 1, Page(s) 91–102

Abstract: Aims: Capmatinib, a mesenchymal-epithelial transition factor tyrosine kinase inhibitor, is metabolized by cytochrome P450 (CYP) 3A4 and aldehyde oxidase. In individuals with hepatic impairment, alterations in hepatobiliary excretion and metabolism could ...

Abstract	Aims: Capmatinib, a mesenchymal-epithelial transition factor tyrosine kinase inhibitor, is metabolized by cytochrome P450 (CYP) 3A4 and aldehyde oxidase. In individuals with hepatic impairment, alterations in hepatobiliary excretion and metabolism could lead to higher capmatinib exposure. We compared the pharmacokinetics of a single oral dose of capmatinib 200 mg administered to participants with varying degrees of hepatic impairment vs. matched controls with normal hepatic function. Methods: This phase 1, multicentre, open-label, parallel-group study enrolled adult participants with normal hepatic function and mild, moderate and severe hepatic impairments. Eligible participants received a single oral dose of 200 mg capmatinib. The pharmacokinetic parameters of capmatinib were analysed and compared across participants with impaired and normal hepatic function. Results: Of 31 enrolled participants, 29 had an evaluable pharmacokinetic profile: normal (n = 9); mild (n = 6); moderate (n = 8); severe (n = 6). Compared with the normal group, geometric mean (GM) maximum (peak) observed plasma drug concentration after single-dose administration decreased by 27.6% in the mild group (GM ratio [GMR] = 0.724; 90% confidence interval [CI]: 0.476-1.10), by 17.2% in the moderate group (GMR = 0.828; 90% CI: 0.563-1.22) and remained unchanged in the severe group (GMR = 1.02; 90% CI: 0.669-1.55). Compared with the normal group, GM area under the plasma concentration-time curve from time zero to infinity decreased by 23.3% in the mild group (GMR = 0.767; 90% CI: 0.532-1.11), by 8.6% in the moderate group (GMR = 0.914; 90% CI: 0.652-1.28) and increased by 24% in the severe group (GMR = 1.24; 90% CI: 0.858-1.78). Conclusion: Mild, moderate and severe hepatic impairment did not have a clinically relevant impact on capmatinib pharmacokinetics. No new safety findings are reported in this study.
MeSH term(s)	Adult ; Area Under Curve ; Benzamides ; Humans ; Imidazoles ; Liver Diseases ; Triazines
Chemical Substances	Benzamides ; Imidazoles ; Triazines ; capmatinib (TY34L4F9OZ)
Language	English
Publishing date	2021-06-18
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.14929
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Article ; Online: Effect of capmatinib on the pharmacokinetics of substrates of CYP3A (midazolam) and CYP1A2 (caffeine) in patients with MET-dysregulated solid tumours.

Chen, Xinhui / Isambert, Nicolas / López-López, Rafael / Giovannini, Monica / Pognan, Nathalie / Kapoor, Shruti / Quinlan, Michelle / You, Benoit / Cui, Xiaoming / Rahmanzadeh, Gholamreza / Mau-Sorensen, Morten

British journal of clinical pharmacology

2022 Volume 89, Issue 3, Page(s) 1046–1055

Abstract: Background: Preclinical studies showed that capmatinib reversibly inhibits cytochrome P450 (CYP) 3A4 and CYP1A2 in a time-dependent manner. In this study, we evaluated the effect of capmatinib on the exposure of sensitive substrates of CYP3A (midazolam) ...

Abstract	Background: Preclinical studies showed that capmatinib reversibly inhibits cytochrome P450 (CYP) 3A4 and CYP1A2 in a time-dependent manner. In this study, we evaluated the effect of capmatinib on the exposure of sensitive substrates of CYP3A (midazolam) and CYP1A2 (caffeine) in patients with mesenchymal-epithelial transition (MET)-dysregulated solid tumours. Besides pharmacokinetics, we assessed treatment response and safety. Methods: This open-label, multicentre, single-sequence study consisted of a molecular prescreening period, a screening/baseline period of ≤28 days and a drug-drug interaction (DDI) phase of 12 days. On day 1 of the DDI phase, 37 patients received a single oral dose of midazolam 2.5 mg and caffeine 100 mg as a two-drug cocktail. Capmatinib 400 mg bid was administered from day 4 on a continuous dosing schedule. On day 9 of the DDI phase, patients were re-exposed to midazolam and caffeine. After the DDI phase, patients received capmatinib on continuous 21-day cycles until disease progression at the discretion of the investigator. Results: A 22% (90% confidence interval [CI] 7-38%) increase in the midazolam maximum plasma concentration (C Conclusion: The data from this study demonstrated that capmatinib is a moderate CYP1A2 inhibitor. Capmatinib administration did not cause any clinically relevant changes in midazolam exposure.
MeSH term(s)	Humans ; Cytochrome P-450 CYP1A2/metabolism ; Caffeine/pharmacokinetics ; Midazolam/pharmacokinetics ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System/metabolism ; Area Under Curve ; Drug Interactions
Chemical Substances	Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; Caffeine (3G6A5W338E) ; Midazolam (R60L0SM5BC) ; capmatinib (TY34L4F9OZ) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Cytochrome P-450 Enzyme System (9035-51-2) ; CYP1A2 protein, human (EC 1.14.14.1)
Language	English
Publishing date	2022-10-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15544
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Article ; Online: Analgesic management of acute pain in the opioid-tolerant patient.

Shah, Samir / Kapoor, Shruti / Durkin, Brian

Current opinion in anaesthesiology

2015 Volume 28, Issue 4, Page(s) 398–402

Abstract: Purpose of review: The management of acute pain in the opioid-tolerant patient is an area in perioperative medicine that is growing, as the use of opioids for chronic noncancer pain has been tolerated in the USA. Adding to this population is an increase ...

Abstract	Purpose of review: The management of acute pain in the opioid-tolerant patient is an area in perioperative medicine that is growing, as the use of opioids for chronic noncancer pain has been tolerated in the USA. Adding to this population is an increase in opioid abusers, addicts and those in recovery and maintenance programmes. These patients will continue to present for surgery and with acute pain that anaesthesiologists and other members of the healthcare team must become more adept at managing. Recent findings: This review covers some of the strategies that may be used by practitioners in the management of acute pain in the opioid-tolerant patient. It is important to collect a detailed history of opioid and drugs of abuse, including the timing of the last dose in order to avoid precipitation of withdrawal. The use of multimodal anaesthetic and analgesic strategies is important for both patient safety and satisfaction and can enhance recovery and discharge home. Summary: There is a need for more high-level evidence-based guidelines to help practitioners achieve the best care of this growing high-risk population of patients.
MeSH term(s)	Acute Pain/complications ; Acute Pain/drug therapy ; Acute Pain/physiopathology ; Adrenergic alpha-2 Receptor Agonists/therapeutic use ; Analgesics/therapeutic use ; Analgesics, Opioid/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antidepressive Agents/therapeutic use ; Drug Therapy, Combination ; Drug Tolerance/physiology ; Humans ; N-Methylaspartate/antagonists & inhibitors ; Opiate Substitution Treatment ; Opioid-Related Disorders/complications ; Opioid-Related Disorders/drug therapy ; Opioid-Related Disorders/physiopathology
Chemical Substances	Adrenergic alpha-2 Receptor Agonists ; Analgesics ; Analgesics, Opioid ; Anti-Inflammatory Agents, Non-Steroidal ; Antidepressive Agents ; N-Methylaspartate (6384-92-5)
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645203-6
ISSN	1473-6500 ; 0952-7907
ISSN (online)	1473-6500
ISSN	0952-7907
DOI	10.1097/ACO.0000000000000218
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Article ; Online: Computational approaches towards understanding human long non-coding RNA biology.

Jalali, Saakshi / Kapoor, Shruti / Sivadas, Ambily / Bhartiya, Deeksha / Scaria, Vinod

Bioinformatics (Oxford, England)

2015 Volume 31, Issue 14, Page(s) 2241–2251

Abstract: Long non-coding RNAs (lncRNAs) form the largest class of non-protein coding genes in the human genome. While a small subset of well-characterized lncRNAs has demonstrated their significant role in diverse biological functions like chromatin modifications, ...

Abstract	Long non-coding RNAs (lncRNAs) form the largest class of non-protein coding genes in the human genome. While a small subset of well-characterized lncRNAs has demonstrated their significant role in diverse biological functions like chromatin modifications, post-transcriptional regulation, imprinting etc., the functional significance of a vast majority of them still remains an enigma. Increasing evidence of the implications of lncRNAs in various diseases including cancer and major developmental processes has further enhanced the need to gain mechanistic insights into the lncRNA functions. Here, we present a comprehensive review of the various computational approaches and tools available for the identification and annotation of long non-coding RNAs. We also discuss a conceptual roadmap to systematically explore the functional properties of the lncRNAs using computational approaches.
MeSH term(s)	Disease/genetics ; Genome, Human ; Genomics ; Humans ; Molecular Sequence Annotation ; Neoplasms/genetics ; RNA, Long Noncoding/metabolism ; RNA, Long Noncoding/physiology
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2015-07-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btv148
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